lReprintedfrom the Journalof the AmericanChemicalSociety,95,8118(1973).]
Copyright 1973by the American Chemical Societyand reprinted by permissionof the copyright owner.
Mechanism of Reaction of Carbon
Monoxide with Phenyllithium'
Larry S. Trzupek, Terry L. Newirth,2 Edward G. Kelly,
Norma Ethyl Sbarbati,sand George M. Whitesides*
Contribution from the Department of Chemistry, MassachusettsInstitute of
Technology, Cambridge, Massachusetts 02139. ReceiuedJuly 14, 1973
Abstract: The product mixtures obtained by reaction between phenyllithium and carbon monoxide in diethyl
ether, followed by hydrolysis, include benzophenone (1). a,a-diphenylacetophenone (2), benzil (3), a,a-diphenyla-hydroxyacetophenone (4), benzpinacot (5), a-hydroxyacetophenone (6), 1,3,3-triphenylpropane-1,2-dione(7),
1,3,3-triphenylpropan-1-one-2,3-diol(8). and benzhydrol (9). Compounds 1, 2, 6,7, and 8 are produced in significant yields i 3,4,5, and 9 are produced in trace quantities. Spectroscopicstudiesestablishdilithium benzophenone
dianion (18) as the first long-lived intermediate formed in this reaction; qualitative correlations between the basicity
of a number of organolithium reagentsand their reactivity toward carbon monoxide suggests,but does not prove,
that benzoyllithium is a precursor of 18. Labeling experiments indicate that the products ultimately isolated
following hydrolysis of the reaction mixture are derived from at least two pathways which compete for the initially
formed 18. One involves combination of l8 with 1 equiv of phenyllithium and 1 equiv of carbon monoxide,
followed by elimination of I equiv of lithium oxide. yielding 17, the lithium enolate of 2; a secondinvolves combination of 18 with 1 equiv of phenyllithium and 2 equiv of carbon monoxide. yielding 22,the trilithium trianion
of 8. Hydrolysis of l7 yields 2 directly. Hydrolysis of 22 yields 8; reversealdol reactionsinvolving 8 or its precursors generate 1 and 6. The mechanism proposed to account for the major products of the reaction of phenyllithium and carbon monoxide is outlined in SchemeIII" On the basis of this scheme,plausible paths to the minor
products of the reaction are proposed.
he addition of nucleophilesto carbon monoxide,
activated by coordination to metal ions, forms the
basis for a thoroughly explored and useful class of reactions. Transformationsrelatedto the hydroformylation process,4additions of organolithium reagents to
metal carbonyls,scarbonylation of mercury(ll) salts,6
organoboranes,Tand organocopper reagents,8metal(1) Supported by the National Institutes of Health, Grants GM
1 6 0 2 0a n d H L - l 5 0 2 9 , a n d b y t h e U . S . A r m y R e s e a r c hO f f i c e( D u r h a m ) ,
G r a n t A R O - D - 3 I - l 2 4 - G6 9 .
(2) National ScienceFoundation Trainee, 1968-1969.
(3) Fellow of the Consejo Nacional de InvestigacionesCientificas y
T e c h r ri c a s .| 9 6 5- l 9 6 6 .
( 4 ) M . O r c h i n a n d W . R u p i l i u s , C u t a l . R e u . , 6 , 8 5( 1 9 7 2 ) ; J . F a l b e ,
" C a r b o n M o n o x i d e i n O r g a n i c S y n t h e s i s , "C . R . A d a m s , t r a n s l a t o r ,
Springer-Verlag,Berlin, 1970,and referencescited in each.
( 5 ) E . O . F i s c h e r ,a n d A . M a a s b i j l , C h e m . B e r . , 1 0 O , 2 4 4 5( 1 9 6 7 ) ,
M. Ryang, L Rhee, and S. Tsutsumi, Bull. Chem.Soc. Jap.,37,341
(1964); S. I(. Myeong, Y. Sawa, M. Ryang, and S. Tsutsumi, ibld.,
38, 330 (1965); W. F. Edgell,M. T. Yang, B. J. Bulkirr,R. Bayer.and
N . I { o i z u m i ,J . A m e r . C h e m .9 o c . , 8 7 , 3 0 8 0( 1 9 6 5 ) ; D . J . D a r e n s b o u r g ,
a n d M . Y . D a r e n s b o u r g ,I n o r g . C h e n t . ,9 , 1 6 9 l ( 1 9 7 0 ) ; N { . R y a n g ,
O r g a n o m e t a lC
. h e m .R e u . ,S e c t . A , 5 , 6 7 ( 1 9 7 0 ) ,a n d r e f e r e n c e sc i t e d i n
cach.
( 6 ) W . S c h o e l l e r ,W . S c h r a u t h ,a n d W , E s s e r s ,C h e n t . U e r . , 4 6 , 2 8 6 4
(1913); T. C. W. Mak and J. Trotter, J. Chem. 9oc.,3243 (1962):
J. M. Davidson,,IC
. h e m .S o c .A , 1 9 3 ( 1 9 6 9 ) .
( 7 ) M . E . D . H i l l m a n , J . A m e r . C h e m .S o c . , 8 4 , 4 7 1 5( 1 9 6 2 ) ; H . C .
B r o w n ,A c c o u n t sC h e m .R e s . , 2 , 6 5( 1 9 6 9 ) .
(8) J. Schwartz, TetrahedronLett.,2803 (1972).
catalyzed oxidative coupling of amines with oarbon
monoxide,e and metal-catalyzedoxidation of carbon
monoxide in aqueoussolution,l0each involve the attack
of formally anionic groups on metal-coordinated
carbon monoxide. Acylmetallic compounds have either
been inferred or identified as intermediatesin many of
thesereactions,and this classof substanceprovides the
foundation for discussionsof their mechanisms.l'5
The reactionsof nucleophileswith free or weakly coordinated carbon monoxide are less well understood.
alcohols and
Base-catalyzed carbonylation of
and the reacti ons of organol it hium , r 3
ami nes,11,12
(9) W. Brackman, DiscussF
. araday Soc.,No. 46, 122 (1968); K.
I ( o n d o , N . S o n o d a ,a n d S . T s u t s u m i ,C h e m . L e t t . , 3 7 3 ( 1 9 7 2 ) .
( 1 0 ) A . C . H a r k n e s sa n d J . H a l p e r n ,J . A m e r . C h e m .S o c . , 8 3 , 1 2 5 8
(1961); S. Nakamura and J. Halpern, ibid.,83,4102(1961).
( 1 1 ) F o r e x a m p l e s ,s e eH . W i n t e l e r , A . B i e l e r , a n d A . G u y e r , H e l a .
C h i m . A c t a , 3 7 , 2 3 7 O, 1 ' 9 5 4 ) ;J . G j a l d b a c k ,A c t a C h e m .S c a n d . , 2 . 6 8 3
( 1 9 4 8 ) r R . N a s t a n d P . D i l l y , A n g e w . C h e m . ,I n t . E d . E n 9 1 . , 6 , 3 5 7
(1967).
(12) Thc reverse reaction, decarbonylation of formate esters and
formarnideswith base,has been examined by J. C. Powers, R. Seidner,
, n d H . J . B e r w i n , J . O r g . C h e m . , 3 1 , 2 6 2 3( 1 9 6 6 ) . A
f . G . P a r s o n sa
formally related transformation, the McFadyen-Stcvens reaction,
h a s b e e n r e v i e w c d b y M . S p r e c h e r ,M . F e l d k i m e l , a n d M . W i l c h e k ,
i b i d . , 2 6 , 3 6 6 4 ( 1 9 6 1 ) ;M . S . N e w m a n a n d E . G . C a f l i s c h ,J . A m e r . C h e m .
S o c . ,8 0 , 8 6 2( l 9 5 8 ) .
( 1 3 ) M . R y a n g a n d S . T s u t s u m i ,B u l l . C h e m .S o c . J a p . , 3 4 , 1 3 4 1
Journal of the American Chemical Society I 95:24 I Nouember 28, 1973
8 1l 9
-sodium,18'leand -zinc2oreagentswith
-magnesium,11-17
carbon monoxide require nucleophilic attack on carbon
monoxide in the absenceof the obvious activation provided by coordinating transition metal ions. Stabie
acyl derivatives of group Ia and IIa metal ions are not
well-characterized entities, although they have been implicated in reactions betweencarbon monoxide and tertbutyllithiunl,2l trimethylsilyllithium,22 and various
lithium amides.23'24
The work reported in this paper was initiated in the
hope that a study of the reaction of carbon monoxide
with phenyllithium would provide evidencebearing both
on the stability of acyllithium compounds and on the
mechanisms of the reactions between organometallic
derivatives of group [a and Ila metal ions and that it
might suggest new approaches to the generation of
nucleophilic acyl groups.25 In fact, no evidence for
longJived acyllithiun compounds as intermediates in
this reaction has been obtained, although the existence
of these substancesas transitory intermediates is suggestedby certain of the data that follow. Nonetheless,
these data establish the basic sequencesfollowed in the
reaction between phenyllithium and carbon monoxide,
outline a number of interesting transformations involving benzophenone ketyl, benzophenone dianion, and
related materials, and suggestnew ways in which carbon
monoxide might be used in synthesis.
benzene in pentane solution.28gave similar product
distributions but were heterogeneousin the latter stages
of reaction. The quantity of carbon monoxide absorbed when the reactions were allowed to proceed to
completionvaried with reactionconditions,but typically
ca.0" 8-1.0equi v of carbon monoxi dew as consum edper
equivalent of phenyllithium.
Hydrolysis and glpc analysisof the reaction mirtures
led to identification of a number of products: benzophenone (1), a.a-diphenylacetophenone(2). benzil (3).
a.a-diphenyl-a-hydroxyacetophenone(4), and traces
of benzpinacol(5) and benzhydroi (9). Careful thinlayer chromatography of the nonvolatile products of
the hydrolysis permitted isolation of a-hydrox\acetophenone(6) and two compounds assignedthe structures
(7) and l .i .-1- t r iphe1.2,3-tri phenyl -1,2-propanedi one
(8) on the basis t'ri erinyl-2,3-dihydroxy-1-propanone
dence outlined below. Certain of these products. t)t
oo
1. CO (1 atm),Et'.,O ll
il
phl-i ---------------PhcPh + PhccHPhz *
2'Hro
z
r
o o
lllllll
phc-Cph
(1961); 35, ll2l (1962)i Trsns.N. Y. Acad. 9ci.,27,724 (1965);
Nippon Kagaku Zasshi, 82, 880 (1961); Chem. Abstr., 58' 12587b
(l 963).
(14) F. G. Fischer and O. Staffers,Justus Liebigs Ann. Chem., 500,
2s3 (1e33).
(15) K. V. Puzitskii, Y. T. Eidus, and K. G. Ryabova, Izu. Akad.
N a z k S S S R , S e r . K h i m . , 1 8 1 0( 1 9 6 6 ) ; C h e m .A b s t r . , 6 6 , 9 4 6 3 l u ( 1 9 6 7 ) .
(16) M. S. Kharasch and O. Reinmuth, "Grignard Reactions of
Nonmetallic Substances," Prentice-Hall, New York, N' Y., 1954, pp
910-9 13.
(17) M. Ryang and S. Tsutsumi, Nippon Kagaku Zasshi,82' 878
( 1 9 6 1 ) ; C h e m .A b s t r . , 5 8 ,1 1 3 8 7( 1 9 6 3 ) .
( 1 8 ) M . S c h l o s s e rA
, n g e w . C h e m . ,I n t . E d . E n 9 1 . , 3 , 2 8 7 ( 1 9 6 4 ) ; M .
Ryang, H. Miyamoto, and S. Tsutsumi, Nippon Kagaku Zasshi, 82,
1 2 7 6 ( 1 9 6 1 ) ; C h e m .A b s t r . , 5 8 , 1 1 3 8 7( 1 9 6 3 ) .
(19) G. Wittig, L. Gonsior, and H. Vogel, JustusLiebigs Ann. Chem.,
688,1(1965).
( 2 0 ) M . W . R a t h k e a n d H . Y u , . / . O r g . C h e m . , 3 7, 1 7 3 2 ( 1 9 7 2 ) .
(21) P. Jutzi and F. W. Schrtjder, J. Organometal. Chem., 24, I
(1970).
( 2 2 ) P . J u t z i a n d F . W . S c h r i j d e r , i b i d . , z 4 , C 4 3( 1 9 7 0 ) .
( 2 3 ) P . J u t z i a n d F . W . S c h r b d e r ,A n g e w . C h e m . ,I n t . E d . E n g l . , l O ,
339 (1971): U. Schtjllkopf and F. Gerhart, ibid., 6,805 (1967). See
a l s o U . W a n n a g a ta n d H . S e y f f e r t i, b i d . , 4 , 4 3 8 ( 1 9 6 5 ) .
(24) The structurally related lithium aldimines are stable at low
temperatures: H. M. Walborsky and G. E. Niznik, J' Amer. Chem.
Soc., 91, 7778 (1969); H. M. Walborsky, W. H. Morrison, III, and
G. E. Niznik, ibid., 92, 6675 (l 970).
( 2 5 ) D . S e e b a c hA
, n g e w . C h e m . , I n t . E d . E n g 1 . , 8 , 6 3 9( 1 9 6 9 ) .
(26) H. Gilman, E. A. Zoellner, and W. M. Selby, J. Amer. Chem.
Soc.,55,1252(1933).
(27) G, Wittig, F. J. Meyer, and G. Lange, JustusLiebigs Ann. Chem..
5 7 1 , ,t 6 7 ( 1 9 5 1 ) .
+ PhCCPh2
+ Ph2C-CPhr *
34s
ooo
ptr$cu,ou+ pn[ScnPhz*
Results
Products. At -78o, phenyllithium in diethyl ether
solution reacts over ca.6 hr with carbon monoxide at I
atm pressure; reaction at 0o is complete in 3-4 hr.
The phenyllithium solutions used in most of the reactions in this study were obtained by reaction of bromobenzene with lithium metal and contained lithium
bromide:26 the reactions of these solutions with carbon
monoxidewere homogeneousthroughout. Carbonylation of analogous lithium halide free solutions of
phenyllithium, prepared by transmetallation of diphenylmercury(I[) with lithium metal2T or by metalhalogen exchange between r-butyllithium and iodo-
oHoH
ooH
67
OH
OOH OH
llll
PhCCH-CPh,+ PhCHPhrl t
89
their analogs,have been reported in previous investigations of the reactions of carbon monoxide with marn
group organometallics.13-22 If reaction mixture S 3rc'
quenched with acetic anhydride before hydrolysis, onlr
two major products are isolated: l-acetoxy-1,2,1-triphenylethylene (10) and l-benzoyl-1-acetoxy-2'2-diphenylethylene (11). The combined yield of thesc'
o
phli
r c'o (r atm).Et,o
''
2AcrO
Ph...
):/
/
AcO
,Ph
\
Ph-4
+
tr<
/
,Ph
\
Ph
l0
AcO
Ph
1l
materials is approximately 50-60/": 10 dominates at
room temperature,Ll at low temperature.
An authentic sample of compound 7 was prepared
using a scheme based on the directed aldol reaction2e
and in low yield by oxidation of 1,3,3-triphenyl-1propene with potassium permanganate in acetic anhydride (Scheme I).30 This substancecould most conveniently be obtained by the hydrolysis of the LL, isolated on quenching the reaction of phenyllithium and
carbon monoxide at room temperature with acetic anhydride. We were not successfulin preparing a sample
of compound 8 by independent synthesisbecauseof the
ease with which this compound undergoes a reverse
(28) M.
Schlosser and V. Ladenberger,
J. Organometal.
Chem,, 8,
r 93 fl967).
(29) H. Reiffin "Newer Methods of PreparativeOrganic Chemistry,"
V o l . V I , W . F o e r s t , E d . , A c a d e m i c P r e s s ,N e w Y o r k , N . Y . ' 1 9 7 1 '
p48tr.
( 3 0 ) K " B . S h a r p l e s sR
, ' F. Lauer, O' Repic' A. Y' Teranishi, arrd
D . R . W i l l i a m s . J .A m e r . C h e m .S o c . , 9 3 , 3 3 0 3( 1 9 7 1 ) .
l4thitesides, et al. f Mechanism
oJ' Reaction
of Carbon Monoxide
with Pheny'llithiwn
8120
meric iorm having the carbonyl group at C'2 and a
hydroxyl at C-l.
Table I lists representative product yields observed
of Products
I. Synthesis
of AuthenticSamples
Scheme
(
'Y4 o
t'-1.-
NI,i
Ph
OAr
\/
\-/
/\
Ph
2. AcrO
s2%
Ph
TableI. ProductYields( [) from the Reactionof
Monoxidein DiethylEther"
with Clarbon
Phenyllitnium
Ph
Temp.'C
I
Ph
\\
+
//-\rt
1
\.J
21
0
-2('r
-70
-7(t
I cH3Li
z. ph2CO
nr r
3 H'so{
LX
460/;
12
Ph
Ph
Hroz
\.
/t
U
\\
\L-
oi
)---c
/ / v -Ph
o
Pf
56qr
Px
Ph
14,
i
:6509
43
16
4
3;
-1r600
26d7A0
t
O
I
0
I'hLi
i co -70-
)<
}-l.i
-7\.
)i,
,/--ir
-
Ph +--
,!
6,1o,l
t,r
HCI
\.
15
\lH3oI!
60".
\.
\rr
Pli
KM rr0o
i'HPh
\>- Ph
i'
ptr
\.
ll
Ol,i
\./
Ac"O
((/
(r
2 Ac"o
Ph
OAc
At:-C)
i,'t,
ir-r,()
I ,i"
I'h' \
0
F-r / /
/i
(J
('lJI)i:
:
16
. e s p e c tra lc h a r acterl s'
a l d ol r eac t ion, 3t n o n e th e l e s sth
tics of this substance,comblnec: with its ongin ani
ch e m is t r y .leav e no d o u b t c o n c e rn i n gth e e s s e ntraiei eme n t s of it s s t r uc tu re . Its n mr s p e c tru m s h o w s tw (-,
drstinctOH resonances,one broad at"6 5.6, onc sharp at
in additrorr
fi 3.8, and one aliphatic CF{ singlet at I -1,.I2,
to aromatic absorptions; the presenceol the hydroxyi
is confirmed by its infrared spectrum. The mass
spectrum of 8 (70 eV) has no detectable parent"ion but
displays prominent peaks at 183 (Ph2COH! ), l8Z
(PhrCO. +), and 105(PhCO+). The one puzzlingfeature
of the speatral data for this substanceis a carbonyl infrared absorption at 17l0 cm--i. The unexpectedlv
high frequency of this absorption may be due to a pref'erenceof 8 for a conformation in which a carbonyl C-l
is twisted out of conjugation with the geminal phenyl
group or, less probably, to the existenceof I in the tauto(31) Compounds i and ii were prepared in attempts to synthesize
ph
,,oH
\/"/
AcO-+-CH
-\-
/
/
\__
PhPh*,i
0H
Pir
HO-)--CH Pii
DL
/
V_"
o'J
I
7cl
-0.5 and
" Phenyllrthiurnsolutionshad concentrationstretween
-1"0 lV and contained-l equiv of lithium brornideper equiv of
phenyllithium Blank entries were those not measured" Yields
were determined by glpc, except when noted otherwlse. b Determined as krenzpinacol.following acid-catalyzedpinacol rearrangement. . Anal-vsesfor 6. 7, and I were only carried out in the ex.periment listed rn the lasi row of this table. d Obtained using
isotopicdilutrontechniques;seethe text for a discussion.
in the reaction of phenyllithium
Ph
fid
lt
9. Efforts to remove the protecting groups fron: thescsubstancesunder
a variety of conditions led only to fragmentation to l, 6, and other
products. Details of these proceduresand of other attempted routes
to I may be found in the Ph.D. Thesis of T. L. Newirth, Massachusetts
lnstitute of Technology, Cambridge,Mass., 1971.
with carbon monoxide
in ether. Yields of 1-5 in the first four entries in the
tabie were obtained using unexceptional glpc techniques.
The yielcis of 1 and 6 in the last entry were obtained by
isotopic dilution. usrng a combination of tlc and mass
spectroscopir techniques. Compounds 6, 1, and S
'De
assavcddirectly by any glpc technique we
could not
Instead, phenyl-d5-lithiumwas aldevise.
able
to
were
lowed to react to compietion with carbon monoxideand th' i reactl on mi xture w as hydrol yzed. Knowr r
quantities oi nondeuterated1,6, 1, and S vlerr' added
to the reaction mixture, and the resulting rrrixtttre ol
oeutcratec an<l noncieuteratedmaterials was separated
' Ihe
yi el ds of products i n t he r ebv prenaral i vcti c.
actron trf tFrc'pirenyi-d;-lithium with carbon monoxide
wer(' cstrnrated on the basis of the results of mass
spectrai anai vsrsoi the i sotopi c composi ti on o f t hese
rrrixtures Tire ciiffcrencein the yields of 1 observedat
---?0uusing.gipc anti rsotopic dilution analysesis easily
rationaiizec on trtc assumption that 8 decornposesln
part to I in the glpc rnjection port (oide infra\.
The necessrtylor using isotopic dilution techniques
tci determtne yrelds of 6, 7. and I rendered product
distribution stuciies too laborious. to be a practical
rnethocioi approacnrng a study of the mechanism ol
this reaction. Further, product distributions were dii'
ficult to reproduce in detail, and product balances
greater than 80:,; were achieved only under special
circumstances. Nonetheless, two qualitative features
of the observeciproduct distributrons are experimentally
significant and pertinent to the mechanistic discussions
that foliow" First. the yields of 1 and 2 vary in a reproducible way with temperature: Z dominates at
room temperaturs; L dominates at low temperature.
Second, the yields of 1-5 (and presumably 6-8) are
relatively insensitive to changes in reaction conditions
other than tentperature: addition of dimethoxyethane
(DME) or .lV,lf,N',lf '-tetramethylethylenediamine(TMEDA) to these ethereal reaction solutions results in an
increase in the yield of benzil (3) to ca. lof with decreasesof the same magnitude in the yields of 1 and 2,
substituting solutions of lithium halide free phenyllithium for the lithium halide-containing solutions
usually used or changing the concentration of phenyl-
Journal of the American Chemical Society I 95:24 I Nouember 28, 1973
8121
lithium by a factor of 5, resulted only in small changes
in yields. In no caseswere new products detected.
In an effort to establish the fate of the phenyl groups
that do not appear among the characterizedproducts of
the reaction, several reaction mixtures were explicitly
examined for the presenceof a number of compounds
which might plausibly have been produced. Careful
analyses of representative reaction mixtures demonstrated that benzene, benzoic acid, benzaldehyde,
benzyl alcohol, biphenyl, triphenylmethane, triphenylcarbinol, and 1,1,2-triphenylethane-i,2-diolwere not
produced in detectablequantity. The observation that
triphenylcarbinol is not a reaction product is of particular mechanistic significance. Since phenyllithium reacts readily with benzophenone, yielding triphenylcarbinol, under the conditions of these reactions, the
absenceof triphenylcarbinol as a product indicates that
benzophenonedoes not appeor in the reaction mixture
until phenyllithium has been completely consumed.
This conclusion was strengthened and extended by
determining indirectly the quantity of benzophenone
present in solution on completion of the reaction between phenyllithium and carbon monoxide before
hydrolysis. An aliquot of a reaction solution that had
been allowed to react to completion with carbon
monoxide at room temperature was treated with lithium
aluminum hydride, then hydrolyzed. The yield of
benzophenoneobserved in the hydrolyzed solution was
indistinguishablefrom that observedin a second aliquot
of the original reaction mixture that had not been
treated with lithium aluminum hydride. Since anv
o
r. LiArHi
/
ll
PhCPh (490/0)* others
" "i-
o
\ lLl" ' *
P h C P h ( 4 8 0 / 0 )*
others
benzophenone present before hydrolysis would have
been reduced to benzhydrol by LiAlH4, this experiment
establishesthat the benzophenoneobservedas a product
in these reactions is not present in the reaction mixture
before hydrolysis.
One additional useful datum can be derived from
studiesof the products of the reaction; uiz, since 1,2,2triphenyl-1-acetoxyethylene (10) replaces 2 in room
temperature reaction mixtures quenched with acetic anhydride, the immediate precursor of 2 before hydrolysis
is probably the corresponding lithium enolate 11.
Ph
OAc
Ph
,\c,O
,}:(
Ph
Ph
t0
\
OLi
/ -\
,/\
,/
Ph
Ph
77
g
Phrl
\"u-!"
\
/\
pi,
Ph
2
Similarly, the observation that 1, 6, and 7 are replaced
by 11 on treatment of product mixtures obtained at low
temperature suggeststhat these materials share a common precursor. Confirming this suggestionand identifying the structure of the precursor is one focus of the
work that follows.
Dilithium BenzophenoneDianion (18) and Lithium
BenzophenoneKetyt (19). The first substantial evidence
concerning the nature of the intermediates in the reaction of phenyllithium and carbon monoxide emerged
from spectroscopicstudies of the striking color changes
that characterize the reaction. Contact of carbon
monoxide with phenyllithium in diethyl ether or etherDME solutions produces an immediate intense red
coloration in the solution, which persists throughout
the greater part of the reaction. The final stages of
reaction are characterizedby a transition of the solution
color from red to greenishbrown.
Our initial attempts to identify the substance(s)
responsible for the red color were guided by the hypothesisthat benzophenoneand other products containing diphenylmethyl moieties might be derived in some
fashion from dilithium benzophenone dianion (18),
(PhLi), ---g-----..
o
^, . . co -, Ji. PhL,
-PhLi ---- PhCLi :
l- o l'?-
I ll | :r,t* --r*
-r'i*
[encnnJ
l8
l- o l-
o
tl
I l l I u * - : + PhCPh
Lpn('pr'l
I
l9
which forms deep red-purple solutions in ether solution, or from lithium benzophenone ketyl (19). In
principle, carbon monoxide insertion into a phenyllithium dimer would yield 18; alternatively, carbon
monoxide insertion into phenyllithium monomer could
yield a transitory benzoyllithium species which could
be converted into 18 by reaction with a second molecule
of phenyllithium.s2 One-etectronoxidation could convert 18 to 19 and ultimately to benzophenone. In
order to test this hypothesis, it was clearly necessaryto
have available authentic samples of 18 and 19. A1though both 18 and 1,9have been thoroughly studied in
other circumstances,the techniquesused for preparation
of these species, and for their characterization and
identification under the reaction conditions encountered
in these studies, were not entirely straightforward and
are outlined here.
Solutions of dilithium benzophenone dianion in
DME were preparedby reduction of benzophenonewith
an excessof lithium dispersion.33,34Solutions of 19
in DME were obtained by reduction of I equiv of
benzophenonewith I equiv of lithium dispersion,35-38
or by reaction of benzpinacol with excessmethyl- or
phenyllithium. Preparation of these materials in diethyl ether solution were carried out using similar
(32) The state of aggregationof phenyllithium under the conditions
of these experiments is unknown. Vapor-phase osmometry indicates
that halide-freephenyllithium is dimeric in ether [P. West and R. Waack,
J . A m e r . C h e m .S o c . , 8 9 , 4 3 9 5( 1 9 6 7 ) ; s e ea l s o G . E . H a r t w e l l a n d A .
Allerhand, ibid.,93, 4415(1971)l; lithium nmr studies suggestthat it is
monomeric [J. A. Ladd and J. Parker, J. Organometal. Chem., 28, I
( 1 9 7 1 ) 1 . R e g a r d l e s s ,t i t h i u m h a l i d e s a n d l i t h i u m e t h o x i d e s a r e i n c o r p o r a t e d i n t o a l k y l l i t h i u m c l u s t e r s : L . M . S e i t za n d T . L . B r o w n ,
J . A m e r . C h e m .S o c . , 8 8 , 2 1 7 4 ( 1 9 6 6 ) ; D . P . N o v a k a n d T . L . B r o w n ,
i b i d . , 9 4 , 3 7 9 3( 1 9 7 2 ) .
( 3 3 ) A . L e B e r r ea n d P . G o a s g u e n ,B u l l . S o c . C h i m .F r . , 1 8 3 8 ( 1 9 6 3 ) .
( 3 4 ) F o r a l t e r n a t i v ep r o c e d u r e s s, e e( a ) S . S e l m a na n d J . F . E a s t h a m ,
( 1 9 6 5 ) ; ( b ) E . L . A n d e r s o na n d J . E . C a s e y ,J r ' ,
J. Org. Chem.,30,3804
i b i d . , 3 0 , 3 9 5 9 ( 1 9 6 5 ) ,a n d r c f e r e n c e sc i t e d i n e a c h . A l e s s c o n v e n i e n t
p r o c e s s ,b a s e d o n e x p e r i m e n t sd e s c r i b e db y A . M a e r c k e r a r l d J . D .
R o b e r t s l J . A m e r . C h e m . S o c , , 8 8 , 1 7 4 2 ( 1 9 6 6 ) 1 ,i n v o l v e s r e a c t i o n o f
dipotassium benzophenonedianion with ar-rhydrouslithium bromide.
( 3 5 ) W . S c h t e r r ka n d A . T h a l , C h e m .B e r . , 4 6 , 2 8 4 0( 1 9 1 3 ) .
( 3 6 ) W . E . B a c h m a n nJ, : A m e r . C h e m .S o c . ,5 5 , 1 1 7 9( 1 9 3 3 ) .
(37) N. Hirota in "Radical lons," E. T. I{aiser and L. I{evan, Ed.,
I n t e r s c i e n c eN
, e w Y o r k , N . Y . , 1 9 6 8 ,p 5 3 f f .
(38) B. J. McClelland,Chem. Reu.,64,301 (1964); seealso M.
S z w a r c ,P r o g r . P h y s . O r g . C h e m . , 6 , 3 2 3( 1 9 6 8 ) .
Whitesides, et al. I Mechanism of Reaction of Carbon Monoxide with Phenyllithium
8122
Analysesof Product Mixtures Obtainedon Oxidation or Hydrolysis
TableII. Representative
of Solutionsof (PhrCO)-M + and (PhzCO)z-ZM
Compound
Concn, M
Solvent
0.067
DME
Ph2coli2
PhrcoLi
0 .0 2 2
DME
Ph2coLi'
0.006s
Et20
PhrcoLi
o.o12f
EtrO
PhzCONaz
0 .0 6 7
EtrO
PhzCONa
0.20f
EtzO
Method of
preparation
Quenching agent
--Yield,"
PhrCO
aq KOH'
Os
aq KOH.
Or
HrO
Oz
CH3OH-KOH"
Os
aq KOH"
Oz
aq KOH"
Or
90
47
100
0
74
53
100
1
95
47
9l
I
7oPh,CHOH
90
0
49
0
70
(f
47
0
100
0
41
0
by reactionof PhsCOwith a
to i,5'o. I Prepared
or benzpinacol
and areprecise
" Yieldsare lrasedon eitherstartingbenzophenone
with I equivof
wascc. 13. d Prepared
by reactionof 2 equivof methyllithium
dispersion
of alkalimetal. ' ThepH of thesesolutions
underthereactionconditions;these
KOH. / Somefractionof theseketylsmayhavebeeninsoluble
methanolic
benzpinacol." Saturated
concentrations
shouldbetakenasupperlimits(cf,footnote39).
techniques,although the low solubilities of 18 and 19
in this solvent make their solutions particularly susceptibleto accidentalhydrolysisor oxidation.3e
Solutions were analyzedfor 18 and 19 by taking advantageof the characteristicbehavior of thesematerials
on oxidation and hydrolysis. Both dilithium benzophenone dianion and lithium benzophenoneketvl are
o xi diz ed t o benz o p h e n o n eb y m o l e c u l a r o x y gen.33' 34
Hyd r oly s is of dilit h i u m b e n z o p h e n o n ed i a n i o n yi el ds
benzhydrol: h-vdrolysis of benzophenone ketyl with
a q ueousbas e( pH > 1 3 ) y i e l d s a I : 1 m i x tu re o f benzop h e none and ben z h y d ro l . T h u s , i n p ri n c i p l e . comp a ris on of t he y iel d s o f b e n z o p h e n o n ea n d b e nzhydrol
obtained on oxidation and hvdrolysis of aliq-uotsof a
so l u t ionc ont ainin g1 8 a n d 1 9 s h o u l d p ro v i d e a strai ght'
I,hzco .o'
O:
PhrCO<-
,*
tT-
pnrcHoH
lI:C)
19,u*-"r O.5PhrCO
+ 0.5PhrCHOH
forward method of deterntining the concentrationsof
th e ses pec ies : t he y i e l d o f b e n z o p h e n o n eo b tai ned on
oxidation of the solution would rellect the combined
quantities of 18 and 19 present; the yield of benzhydrol obtained on alkaline hydrolysis would correspond to one-half the quantitv of 19 present. This
analytical technique suffers, however, from two an1biguities. First, the extent to which the ketyl 19 is
dimerized in solution, particularl;,-at the relatively high
concentrations used in this work. is unclear;40 thus.
( 3 9 ) S o l u b i l i t y o f b o t h 1 8 a n d 1 9 i n e t h e r e a is o l v e n t si s l i m i t e d : 1 8
a p p e a r st o p r e c i p i t a t ef r o m s o l u t i o n so f D M E a t a m b i c n t t e m p e r a t u r e s
a t c o r l c e n t r a t i o n s; 0 . 0 6 7 M , a n d f r o m s o i u t i o n so f E t r O a t c o n c e r l t r a tions 10.0065 M; thelimiting soiubility of l9 in DME is ? 0.06 M,'
i n E t r o i t i s t 0 . 0 0 3M .
( 4 0 ) A l t h o u g h I 9 i s a p p a r e n t l y m o n o m e r i c i n d i o x e r r - rseo l u t i o n a t
1 0 - 3 - 1 0 - 4 M c o n c e n t r a t i o n s , a itt s v i s i b l e a b s o r p t i o n i n d i c t h y l c t h e r
s h o w s s i g n i f i c a n tc i e v i a t i o n sf r o m B e e r ' sl a w . a : N o b e n z p i n a c o li s o b s e r v e do n h y d r o l y s i s o f l 9 u n d e r b a s i c c o n d i t i o n s , i n t r g r e c m c n tw i t h
e a r l i e r w o r k ; 3 5 ' 3 { 'n o l l e t h e l e s sb, e c a u s eb e . z p i r l a c o l i s r a p i d l y c l e a v e c i
t o b e n z o p h e l l o n ea n d b e n z h y d r o lb y b a s e ,t h i s o b s c r v a t i o r .i rs n o t u s e f u l i n d e t e r m i n i n ga n e q u i l i b r i u r nc o n s t a n tf o r d i m e r f o r m a t i o n .3 6 ,83
( 4 1 ) H . V . C a r t e r , B . J . M c C l e l l a n d ,a n d E . W a r h u r s t , T r a n s .F a r a d a y
S o c . , 5 6 , 4 5 5( 1 9 6 0 ) ; f o r r e l a t e ds t u d i e so f s o d i u m b e n z o p h e n o nkee t y l ,
s e eD . J . M o r a n t z a n d E . W a r h u r s t ,i b i d . , 5 l, l 3 7 5 ( 1 9 5 5 ) ; N . H i r o t a
a n d S . I . W e i s s m a ,nJ . A m e r . C h e m .S o c . ,8 6 , 2 5 3 8( 1 9 6 4 ) , S e ea l s o D .
H . E a r g l e ,J r . , a n d R . E m r i c h , J . O r g . C h e m . , 3 5 , 3 7 4 4( 1 9 7 0 ) ,f o r a n
i r - r t e r p r e t a t i oonf t h e i r s p e c t r u mo f l 9 i n D M E .
( 4 2 ) H . E . B e n t a n d A . J . H a r r i s o n , J . A n t e r . C h e m .S o c . , 6 6 , 9 6 9
( 1 9 4 4 ) . T h e v i s i b l e s p e c t r u m o f s o d i u m b e n z o p h e r r o n ek e t y l o b c y s
B e e r ' s l a w a t - 1 0 - { M i n D M E b u t d e v i a t e si n d i e t h y l e t h e r ; t h e
the yield of benzhydrol obtained on basic hydrolysis is
probably best considereda measureof the total quantity
of monomeri cand di meri c 19 rather than a di re ct m easure of monomeri c l 9 al one. S econd,si ncei t has not
been possible to prepare samples of either 18 or 19
unambi guousl y.i t has not been possi bl eto pro ve t hat
either hydrolysis or oxidation lead quantitatioely to
the indicated products. Thus the concentrations for
18 and 19 inferred from these analyses should be
taken as minimunr values. Nonetheless, several experimental observattonssuggestthat determination of
the relative ,vieldsof benzophenoneand benzhydrol obtained following hydrolysis and oxidation of a solution
contai ni ngl 8 and 19 does i n fact provi de a rea sonably
accuratemethrtd for determining the concentrationsofl
these compounds. Fi rst, the yi el ds of benzophenone
and benzhl ' droiobservedon oxi dati on or hydr olysisof
solutions oi' l8 and 19 prepared by reduction of benzophenone w i th appropri ate quanti ti es of l i thi um m et al
for 85 100% of the starting material (Table
accoLrnr.
II). Further. the product bal ancesobtai nedon hydr olysi s anci oxi dati on of ai i quots of a common solut ion
agree w el l . Ti rus. i t appearsthat both reactionst ake
place in high vield. Second,the ratio of benzhydrol to
benzophenonc obtained on hydrolysis of solutions
ostensi bl ycontai ni ng benzophenonedi ani on i s ( 0. 01,
w hi i e thi s rati o for sol uti ons ostensi bl y cont aining
ketyl rangesfrom 0.87-0.95,i n reasonable
benzophenone
agreementwith the expectedvalue of 1.00. Third, the
spectroscopicexarninations described below establish
that reduction oi benzophenonewith I equiv of lithium
yields a solution which contains benzophenone ketyl
but little if any benzophenonedianion and that continued reduction using an excessof lithium yields solutions containing benzophenonedianion but little benzophenone ketyl. Taken together, these results indicate
that reduction oi even high concentrations of benzophenonewith appropriate quantitiesof lithium metal in
ethereal solvents yields solutions containing 18 and 19
in good yield, uncontaminatedby important quantities
of other materials, and that comparison of the yields
e q u i l i b r i u m c o r l s t i t n tf c r r d i m e r i z a t i o n i n t h e l a t t e r s o l v e n t i s - l 0 r l .
mol-r: J. Garst, D. Walmslcy,-C. Hcwitt, W. Richards, and E.
Zabolotny, ibid., 86, 412 (1964). Magnetic susceptibilitymeasurements
i n c l i c a t et h a t s o d i u m b e n z o p h e n o n ek e t y l i s > 9 9 f a s s o c i a t e dt o a
d i a m a g n e t i cf o r m i n b e n z c n e : R . N . D o e s c h e ra n d G . W . W h e l a n d ,
i b i d . .s 6 , 2 0 1I ( 1 9 3 4 ) .
Journal of the American Chemical Society I 95:24 f Nouember 28, 1973
8123
Table III.
Absorption Maxima and Extinction Coefficientsfor OrganometallicSpecies
Method of preparation
Compound
Phcoc(oLiFCPh,
o
,/\
(1s)
Ph,C--.--CHCOPh
PhrC:C(OLi)Ph (17)
Phecoli, (18)
PhrEC(Oec)Ph
Phrco + Li
Phrcol-i (19)
(PhrCOH), + PhLi"
Phc(oli):c(oli)c(cH3)3
Ph3CLi
(20)
+ LiTMP
+ PhLi"
PhCOCOC(CH')' f excesslithium
Ph3cH + PhLi"
Solvent"
EtrO
DME
DME
EtrO
DME
EtzO
DME
DME
DME
,\ma*, flflt
417
437
288
494
535
600
634
300
435
440,000
25,000
,
" Solutions were 0.1 N in phenyllithium. The literature valuesfor the extinction coefficientof trityllithium in letrahydrofuran is log G
3.97(425 nm)}t " The phenyllithium usedwas that presentin the solvent.
of benzophenone and benzhydrol obtained on oxidation and hydrolysis of these solutions provides a
practical method of analyzing for these substances.
Spectroscopic Studies. The procedures described
were used to prepare samplesof L8 and L9 whose uv and
visible spectra could be compared with those from solutions obtained on reaction of phenyllithium with carbon
monoxide. The spectra of 18 and 19 are strongly
dependent on concentration, on the nature and concentration of associatedmetal ions, and on the polarity of
In order to obtain spectra of 18
the solvent.sT'38'42'43
and 19 that could be compared directly with spectra
taken in the initial stages of reactions between phenyllithium and carbon monoxide, we carried out spectroscopic studies of authentic solutions of 18 and 19 in
ethereal solutions containing approximately 0.1 M
phenyllithium. The use of phenyllithium solution as
solvent has the , additional practical advantage of
minimiiing the effectsof adventious traces of oxygen or
water on the spectra of the benzophenoneketyls and dianions by acting as a scavenger for materials which
would react with these organometallic reagents. The
spectrum of phenyllithium itself does not interfere with
those of the compounds of interest at wavelengths
longer than approximately 300 nm. Visible spectra for
dilithium benzophenone dianion and lithium benzophenone ketyl in 0.1 M solutions of phenyllithium in
DME are given in Figure 1. The spectra of 18 were
obtained with solutions prepared by dilution of concentrated stock solution to -10-3 M; the spectra of
19 were obtained from solutions prepared by a similar
dilution procedure or directly by reaction of benzpinacol with phenyllithium solution in the cuvette.
For comparison, this figure also gives spectra of several
compounds that either are themselvesformed in significant co.ncentration during the reaction (the lithium
enolates of a,a-diphenylacetophenone(17) and 1,1,3triphenylpropane-1,2-dione(15)) or that are spectroscopic models for compounds that are formed during
the reaction (the dilithium dianion of l-phenyl-3,3-dimethylbutane-I,2-dione (20) which is used as a model
for the trilithium salt of 8, Ph2c(oli)c(oli):c(oli)Ph (22) (uide inJra)).aa Absorption maxima and ex(43) For a study of the influence of lithium bromide on the spectrum
o f l i t h i u m b e n z o p h e n o n ek e t y l , s e e D . G . P o w e l l a n d E . W a r h u r s t ,
T r q n s .F a r a d a y S o c . ,5 8 , 9 5 3 ( 1 9 6 2 ) .
(44) Compound 17 was prepared by reaction of 1,2,2-triphenyl-lacetoxyethylene(10) with phenyllithium in the cuvette. Lithium 1,1diphenyl ethoxide formed as the other product of this reaction is transparent in the spectral region of interest. Compound 20 was prepared
(21) with excess
by reduction of 1-phenyl-3-3-dimethylbutane-2,3-dione
o
o
0
o
o
!
A'nm
Figure1. Ultraviolet-visible
spectraof organometallic
species
in
DME solution: (a) the reactionmixture obtainedby adding
phenyllithium
to an excess
of carbonmonoxide
dissolved
in DME;
(b) thereactionmixtureobtainedby addingcarbonmonoxideto a
large excessof phenyllithiumdissolvedin DME; (c) PhrCLi;
(1s)PhCOC(OLi):6phz:Gi) Ph'C:C(OLi)Ph;(20)PhC(OLi):
c(oli)c(cH,)a; (18) Phzcolir; (19) Ph,coLi. Sinceonly the
absorption
maximaandpeakshapes
couldbe determined
with any
from thesespectra,
accuracy
theyarenot drawnto scale,and the
arearbitrary.
absorbances
of thevariousspectra
tinction coefficients (when estimated) obtained from
thesespectraare summarizedin Table III.
These spectra were compared with spectra of solutions obtained by reaction of phenyllithium and carbon
monoxide under conditions approximating those obtaining during the product studies summarized in
Table I. Addition of 0.16 pmol of carbon monoxide to
4 nl of 0.1 N etherealphenyllithium solution in a Pyrex
cuvette at room temperature produced the red coloration characteristic of the initial stagesof the large scale
reactions(Figure 2, curve b); a preciselyanalogousreaction carried out in DME yielded the spectrum shown
in Figure 1, curve b. The similarity of the peak shapes
and absorption maxima of the light absorbing material
produced in these experiments and of authentic dilithium benzophenone dianion 18 strongly suggests
that the compound formed initially in the reaction of
l i t h i u m d i s p e r s i o ni n D M E ( s e €t h e E x p e r i m e n t a lS e c t i o n ) . C o m p o u n d
l 5 w a s o b t a i n e d b y r e a c t i o n o f 1 , 1 - d i p h e n y l - 2 - b e n z o y l e t h y l eonxci d e
eiTMP).nr The spectrum
w i t h l i t h i u m 2 , 2 , 6 , 6 - t e t r a m e t h y l p i p e r i d i d( L
of lithium tripher-rylmethide,prepareC according to the procedure of
R . W a a c k a n d M . D o r a n , J . A m e r . C h e m .S o c . , 8 5 ,1 6 5 1( 1 9 6 3 ) ,i s a l s o
i n c l u d e di n F i g u r e l .
( 4 5 ) R . A . O l o f s o n a n d C . M . D o u g h e r t y , J . A m e r . C h e m .S o c . , 9 5 ,
5 8 3( 1 9 7 3 ) .
iAhitesides, et al. I Mechanism of Reaction of Carbon Monoxide with Phenyllithium
8124
experiments is that dilithium benzophenonedianion 18
is formeci at the outset of the reaction of phenyllithium
i
with carbon monoxide. Lithiurn benzophenone ketyl
may be present in the reaction mixture late in the rea.rL
action.
Reactions of Dilithium Benzophenone Dianion with
Carbon Monoxide in the Presence of Phenyllithium.
Although these spectroscopic studies implicate dilithium benzophenone dianion as the principal substance generatedin the initial stage of these reactions, it
remained to establish the role of this compound in the
formation of the products actually isolated as their
conclusiorr. In particuiar, it was important to know
whether th e lithium enolate of cc,a-diphenylac':tophenone
(17) observed as the major reaction product at room
temperature was derived from 18 or from pirenyllithium
by sorne reaction path not involving 18 and to deterFigure2. L/ltravioiet-visible
spectraof organometallic
species
in
mine
whether 18 could plausibly give rise to benzodiethylethersolution: (a)thereactionmixtureobtained
by adding
phenone,
the major iow-temperature product, under the
phen-vllithrum
to an excess
of carbonmonoxide
dissoived
in ether;
(b) thereactionmixtureobta.ined
reaction conditions used in this work.
by addingcarborimonoxide
to a
largeexcess
of phenS,llithium
dissolved
in ether;(15)IThCOC{OLi)-=
It was possible to establish by simpie labeling experiCPiiz;(18) ['hrCOI-ir;(t9) PhzCOl-i.Tlie absorlrances
of the
ments that the benzophenone moiety of benzophenone
spectra
arearbitrar,"-.
dianion was incorporated into both high- and iowtemperature products on reaction with phenyllithium
and carbon monoxide, For this purpose.we usecl4,4'phenyllitirium and carbon monoxide is in tact diiithium
di-terr-butyli:enzophenone(23) as the latreled benzoLrenzophenone
dianion; none of the eithercomrrounds
ohenone rather than 2F{- or 1aC-labeledmaterial, beexamined (1.5, 17, or 20) overlapped ttre absorption
cause thc dilithium dianion, 24., of this substituted
region for this clianionsufficientivto hamper its identifiL,enzophenonewas lnuch more soiuble in ethereal solcation. Comparison of the a bsorptivity observeciin"the
vents, and henceeasierto prepareand manipuiate, than
soiution resulring frorn reacrion or phenyliithium and
was dilithiunr benzophenonedianion itself. Reaction
carbon monoxide wit!: that estimated i'rom the extincof 7A with carLronrnonoxidein the preseneer'f a tenfoid
tion coefficientof 18, determineciindepencjentil',and the
excesscrf phenyllithiuni. foiiowed by queni:rr';lg of the
quantity of carbon monoxicle used in the reaction ir-lreaction rnrxture with acetic anhydride, leci to subdicates that the amount of, lB fbrmecl acoounts for
.'*,50% of the carbon monoxide adcleo.
stantial incorporations (-60 %) of the iabeled benzophenone moiety into the products 25 and 26, the exln an effort to generate spectra characteristic ol" thc
pectedanai ogsof 10 and 1L;anyi el dsof 10, 11, 25, and
cornpoundspresentlate in tire reaction betweencari:on
26 obtained in severai reactions are summarized in
monoxide and phenyllithiurn, a small ciuantirv of
p h e ny liit hiun,was a d d e d to c u v e tre sc o n ra i n i n g ti Ml
*Ph-tcH,,t,c{==-),or ether saturated with carbon monoxide (F'igure j.,
\_l
curve a and Figure 2" curve a, respectively)" Tl.re
r' co Et2o>
maxinra of two prominent long waveiengtir oands obi*ph.col'-2i,i- + 10phLi
2
. Ac"O
served in the visible spectrum in ether corresponct
24
rougirly to those of 18 and 1g; under these condiiions
0
spectra characteristic of L7 and ZZ were otrscured bv
*pi,
"Ph
Pi'
overlap and possibly by other speciesin solution. The
\_r,,
.\/
+
+lo+ll
spectrum in DMF. is not simply interpreted. Estirnates
/<\
*Ph
*Ph
of the conversions of phenyllithium lB and 19 under
OAc
oA.
these conditions, if indeed these were the compounds
25
26
responsible in the region between 450 and 650 nrn,
Table IV. An authentic sample of 26 was prepared by
would not be significanr, since impurities present in the
substitution of 4,4'-di-terr-butylbenzophenone for
ether soiution before addition of phenyllithiurn debenzophenon€in the proceduressummarized in Scheme
stroyed appreciable quantities of the initially formed
I;
authentic 25 was svnthesizedby the procedure outorganometallic materials. Control experiments establined in SchemeIl.
lished that neither l8 nor 19 reacted with phenyrlithiurn
in theseor more concentratedsoiutions"
(461 To establish that these results were independent of the method
To lend further supporr to the contention that 1g is
of labeiing the reaction partners, similar:although less accurate studies
present in reacting mixtures of phenyllithium ancl
were carried out involving ethereal solutions containing 1 equiv of
dilithium benzophenonedianion and 5 equiv of p-ethylphenyllithium.
carbon monoxide, a I M solution of phenyllithiurn was
Exposure ol' these solutions to carbon monoxidc, followed by hystirred under I atm of carbon monoxide for 20 min and
drolysis, led to a,a-diphenyl-p-ethylacetophenone(iii) in 24f yield,
then quenctredby addition of NaOD in DzO. Analysis
t'nr tt'9
by glpc and mass spectral analysis after the usual work[PheC:O]r-21-i+ * SLiPh-p-E,
up indicated the presence of 0.8 /" benzhydrotr,conPhTCHCOPh-p-Et * other products
taining >0.8 deuterium atoms per molecule.
iii
The important conclusion from these spectroscopic
b a s e do n 1 8 "
l-i
Journal of the American chemical society I 95:24 Nouember 2g, IgT3
I
8125
Table IV. ProductsObservedFollowing an Acetic Anhydride
Quench of Product Mixtures from Reactionsof
Dianion (24),
Dilithium 4,4' -Di-terl-butylbenzophenone
Phenvllithium. and Carbon Monoxide
PhLi
(concn,
M)
A
(concn,
M)
0.50
0.25
0.50
0.50
o.25
0.50
0
0.05
0.05
0
0.05
0.05
Temp, --yislfl,o
oc
10
11
25
25
25
-78
-7 8
-7 8
riltill
* P h " c l i+ c + C +
26
00
7 (36)b
6 (62\b Trace
00
4 (z0)b
o
6 (59)b
0
Synthesisof 25
1.
.
*Ph,co
-
PhMeCl
1
.,
-
2. SOCI2, Pyr
'
CH?CO1[I
2. HN{PA, A
79o/o
36%
o,,
*Ph
* P h : Cl l H Cl [P( chH^3 )^2^c -H-] 2- N- -L -i '
-
2.Ac"O
28o^
oAc
\
/
>< \
/
*Ph
-, : .
Ph
25
A-plausible reaction sequencefor the transformation
of 24 to 25 involves initial transformation to an intermediate 21, either by insertion of carbon monoxide into
a mixed organolithium cluster containing units of both
phenyllithium and dianion 24in a manner analogousto
that suggestedfor formation of 18, by nucleophilic addition of 24 to an initially formed benzoyllithium, or by
nucleophilic reaction of phenyllithium with an adduct
of ?A and carbon monoxide.aT Elimination of the elements of lithium oxide from 27 would vield the lithium
enolate of 25.4e
o]-i
I
*Phcl,i
+
I
"Ph
24
O
lll
\t I
*Ph-l
| |
OO
O
l l -- ' , ,
llll
-P h, CHCCPh
i -cu-C P h
28
,.nI
L-
a:B
Aco
oAc
o-lcl
f
| \l
I l)
l*Ph.c-c:cPh
AcO
O
l
* P h,c:c-l lcPh
|+
26
l
29
inally present in24, would in turn yield 26. Since the
acetoxy group required to leave in this last step is
activated toward heterolysis by two adjacent phenyl
groups and one oxygen-substituted B-styryl moiety,
sufficiently rapid conversion of 29 to 26 to preclude isolation of 29 would not be surprising; however, alternative schemesfor conversion of 28 to 26 involving, €.8.,
monoacylation of the oxygen derived from 27 followed
by rapid loss of acetateion, can of course also be written. We have no direct evidence for 29 or related
speciesin these reactions,but the postulation of 28 as
an intermediate is immediately compatible with the
formation of compounds l, 6, 7, and 8 as hydrolysis
products from the reaction of phenyllithium and carbon
monoxide by protonation, dehydration, and reverse
aldol reactions, starting from the analogous triamon 22.
The differencein the observedvields of 1 and 6 from
ot,i ot,i ol.i
2PhLi + :lco +
lll
I,h_(._(':cPh
22
lH'o
H,O
-"Li ,o"
\i-Ph
*Ph
H ' o.* P h
+
AoLioli
c * LiPh*
OHOH
tlt
* P hrc
-c:cP h
" Yields were determinedby glpc and are basedon phenyllithium
unlessnoted. b Yield basedon24.
SchemeII.
[,iPh -
24
ol i ol i ol -i
/25
39
14
32
16
34
16
060
044
047
olioo
rr Oi H Oii)PhC-{ry-CPh --
Li
8
tf
'tl
27
*tn..t":
*on)a:
----------> ' ,zoA''
rJi
:t
"aott
*ph.'
.rn
ph
,n
;The mechanism for conversion of the diarylmethylene
moiety of ?A to 26 is clearly more complex than that for
the transformation of 24 to 25. Combination of I
equiv of dianion?A,2 equiv of carbon monoxide, and 1
equiv of phenyllithium in a process analogous to that
required to form 27 would generatethe trianion 28, the
labeled analog of 22. Acylation of this substancewith
acetic anhydride, followed by loss of the oxygen orig( 4 7 ) T h e a b i l i t y o f d i s o d i u m b e n z o p h e n o n ed i a n i o n t o a c t a s a
h8
s reactivityof 18
n u c l e o p h i l et o w a r d c a r b o n i s w e l l e s t a b l i s h e d ' 3 a at' 4
shouldbe similar.
( 4 8 ) H . E . Z a u g s a n d R . J . M i c h a e l s J, . O r g . C h e m . , 3 3 , 2 1 6(71 9 6 8 ) .
( 4 9 ) A t t c m p t s t o p r e p a r ea n a u t h e n t i cs a m p l c o f 2 7 w e r e n o t s u c c e s s ful. Nonetheless, reduction of a,cr-diphenyl-a-hyclroxyacetophenone
( 4 ) w i t h e x c e s sd i l i t h i u m b e n z o p h e n o n ed i a n i o n d i d y i e l c l 2 ( - 7 0 % )
a f t e r h y d r o l y s i s . T h u s i t a p p a r e n t l y i s p o s s i b l et o e l i m i n a t c l i t h i u m
o x i d e f r o m a s p e c i e sr e s e m b l i n g 2 7 u n d e r r e d u c i n g c o n d i t i o n s . A
s i m i l a r e l i m i n a t i o n o f l i t h i u m o x i d e i s p r o p o s c dt o o c c u r d u r i n g f o r m a t i o n o f 1 , 2 - d i - t e r t - b u t y l c t h y l e nfer o m t h e r e a c t i o n o f / e r l - b u t y l l i t h i u m
w i t h t e r f - b u t y l e t h y l e n eo x i c l e ; c f . I . K . C r a n d a l l a n d L . H . C . L i n ,
J . A m e r . C h e m .S o c . .8 9 . 4 5 2 ' l ( 1 9 6 7 ) .
O
OH O;H
,.OH
\-l
I
Ph:c1!:cPh
| -u' n
I
OHOH
llll
Ph,C+ CH:CPh
I
oHo
til
PhrC:C -CPh
It
tl
{l
tl
oo
o
tl
HOCH:CPh
6
11
llll
PhrcHCCPh
.,
t
the reaction presumably reflectsthe sensitivity of 6 to
the conditions encounteredduring the hydrolytic workup.
Thus, examinationof productsderived from reactions
of the labeled dilithium diaryl ketone dianion 24 with
phenyllithium and carbon monoxide fully supports the
hypothesi sthat di l i thi um benzophenone18 i s an int er mediate in the reaction of phenyllithium and carbon
monoxi de and provi desa uni fyi ng mechani sti cr at ionalization for most ot' the products of this reaction based
on conversion of 18 to intermediateshaving structures
t7 and 22.
Oxidation of Dilithium Benzophenoneand Lithium
Whitesides.et al. I Mechanisntof Reactionof'CarbonMonoxidewith Phenyllithium
8126
Benzophenone Ketyl by Carbon Monoxide. Benzpinacol (5) and benzil (3) are the sole isolated products
of the reaction of phenyllithium and carbon monoxide
not easily generated from l7 or 22. One possible
rationalization for the formation of 5 rests on the
demonstration that carbon monoxide is a sufhciently
strong oxidizing agentto convert benzophenonedianion
to benzophenone ketyl (and benzophenone ketyl ultimately to benzophenone). Carbon monoxide is an effective one-electron oxidant toward a variety of aromatic radical ions and dianions,s0toward metallic potassium,sr and toward solutions of potassium in ammonia,52yielding in each case substancesthat can be
derived from a hypothetical "alkali metal carbonyl"
M+CO.-.
Chemical and spectroscopicdata demonstrate that
carbon monoxide is also capable of oxidizing 18 and
19 the nature of the products derived from the carbon
monoxide was not establishedin these experiments.
Thus, Table V summarizesthe yields of benzophenone
TableV. Yields of Benzophenone
and BenzyhydrolObtained
by Oxidationof Dilithium Benzophenone
Dianion(18)and
Lithium Benzophenone
Ketyl (19)with Carbon Monoxide,
Followedbv Hvdrolvsis"
Compound
(concn,M)
Solvent
18 (0 06)
18 (0.004)
le (0.05)
19 (0.003)
DME
EtzO
DME
EtzO
Product(%vield)
Ph2CO
PhZCHOH
50
20
52
95
45
6
38
0
' Yields are basedon the initial concentrationof 18 or 19. The
fate of the organic moieties not detectedas benzophenoneor
benzhydrolin theseexperimentswas not established.
and benzhydrol observedfollowing hydrolysis of solutions of 18 and 19 that had been allowed to reacr ro
l9
"5^'N,.
l8
I
\o
t, co. e/
0,,\
l9
l,,o
completion with carbon monoxide under conditions
approximating those utilized for the reactionsof carbon
monoxide with phenyllithium. The observation of approximately equal yields of benzophenoneand benzhydrol, characteristicof 19, after reaction and hydrolysis of either 18 or 19 with carbon monoxide in DME
contrastswith the detectionof benzophenonealone after
reaction and hydrolysis of these substancesin diethyl
ether. The inference from these experiments is that
carbon monoxide will oxidize 18 to 19 in either DME
or ether but will oxidize 19 to benzophenoneat a significant rate only in ether; this inferenceis in qualitative
accord with the supposition that lg should be less
stro n gly r educ ingin th e m o re s tro n g l y s o l v a ti n gD ME
th a n in t he les sbasi ce th e r.
( 5 0 ) W . B l i c h n e r ,C h e m .9 e r . , 9 9 , 1 4 8 5( 1 9 6 6 ) .
( 5 1 ) W . B t i c h n e ra n d E . A . C . L L r c k c n H
, elc. Chim.Actu,47,2l13
( 1 9 6 4 ) ; W . F . S e r g e rA, . F a t i a d i , P . C . P a r k s , D . G . W h i t e . a n c l T . p .
P e r r o sJ, . I n o r g . N u c l .C h e m . , 2 5 , l S 7( 1 9 6 3 ) .
( 5 2 ) W . B l i c h n e r , H e l a . C h i m . A c t o , 4 6 , 2 1 1 1 ( 1 9 6 3 ) ,a n d r e f c r c ' c c s
.
c i t e dt h c r e i r - r .
Qualitatively similar conclusions were reached on
examination of the changesinduced in the visible spectra
of solutions of 18 in ether and DME following exposure
to carbon monoxide. In DME, this exposure results
in disappearanceof the band due to 18 and appearance
of a band at 634 nm attributable to 19; in ether, addition of carbon monoxide results in complete bleaching,
with the only new peak appearing at -350 nm (benzophenone).
Reactions with Other Organometallic Reagents. We
have examined briefly the reactivity of several other
types of organometallic reagentstoward carbon monoxide. These experiments, together with results
obtained by others, indicate qualitatively that only
derivatives of strongly basic anions will react with
carbon monoxide under conditions similar to those
used in the work describedin this paper. Thus, /ertbutyllithiuffi, 2I phenyllithium, n-butyllithium,r,amethyllithium, trimethylsilyllithium,22 and cyclopropyllithiums3readily absorb carbon monoxide, as do dimsyl
sodium and several lithium amides;23 the less basic
lithium phenylacetylide, lithium n-butylacetylide, lithium diphenylamide, lithium cyclopentadienide,l3and
lithium diphenyl phosphideappearnot to react. These
data suggest that in classifying anions according to
their reactivity toward carbon monoxide it may be
heuristically valuable to consider these reactions as
proceeding through acyl anions (30) whether or not
o
lll
B-+('.-
[ fl]
Lu/ )
30
substancesof this classare true intermediates. Values
for pKr,'s of speciescontaining the acyl anion moiety
are not well-established,although that of CHaOzC(30, B : OC H 3) has been esti matedto be ca. 35; sr
this value seems consistent with what little is known
about the chemistry of acyl anions. These organolithium reagents that have so far been found to react
with carbon monoxide all are derivatives of anions
having pKr's of this magnitude or greater, while those
that have proved unreactiveare characterizedby pKu's
that are smaller.ss Thus, it may prove possibleto predict the facility of addition of organic anions to carbon
monoxide on the basis of their basicitv relative to that
of the appropriate acyl anion 30.
Discussion
Three principal kinds of data bear on the mechanism
of the reaction of phenyllithium with carbon monoxide.
First, spectroscopic studies indicate that dilithium
benzophenonedianion is formed in the early stagesof
the reaction. Second,examination of the products of
reactionsof carbon monoxide with a mixture of labeled
( 5 3 ) E . G . I ( e l l y , P h .D . T h e s i s ,M a s s a c h u s e t tl sn s t i t u t e o f T e c h n o l o g y ,
Cambridge,Mass,, 1968. The major products from the reaction of
, l - b u t y l l i t h i u mw i t h c a r b o r -m
r o n o x i c l ei n h e x a n er e s e m b l et h o s ep r o d u c e d
from phenyllithium, riz. dibutyl ketone (3-071, 6-butyldecan-5-one
( 6 0 - 7 0\ ) , a n d 7 - b u t y l u n d c c a n c - 5 , 6 - dni oe ( l 0 % ) .
( 5 4 ) K . P . B u t i n , I . P . B e i e t s k a y aA
, . N . I ( a s h i n , a r - r dO . A . R e u r o v ,
J . O r g a n o m e t a lC
. h e m . ,1 0 , 19 7 ( 1 9 6 7 ) .
( 5 5 ) F o r d i s c u s s i o n so f t h e p K , , ' s o f w e a k o r g a n i c a c i d s , s e e H . F .
E b e l i n " M e t h o d c n d c r O r g a n i s c h e nC h e m i e , " ( H o u b e n - W e y l ) ,V o l .
l 3 / 1 , 4 t h c d , G c o r g T h i e m eV e r l ; r g S
, tuttgarr1
, 9 7 0 ,p 2 7 t r : J . R . J o n e s ,
Q u a r t . R e c . , C h e m .S o c . , 2 5 , 3 6 5 ( 1 9 7 1 ) : D . J . C r a m , " F u r r d a m e n t a l s
o f C a r b a n i o n C h e m i s t r y , " A c a d e m i cP r e s s ,N e w Y o r k . N . Y . . 1 9 6 5 .
C h a p t e rI .
Journal of the Anterican Chemical Societlt I 95:24 I Nouember 2g. 1973
8127
dilithium benzophenone dianion and phenyllithium
establishes that the diarylmethylene moiety of the
former is effectively incorporated into products characteristic of the reaction of carbon monoxide with
phenyllithium. Third, examination of the influence of
temperature and reaction composition on the distribution of products indicates that at. least two related
processes compete in these reaction mixtures: one!
taking place at room temperature, converts 3 equiv
of phenyllithiurn and 2 equiv of carbon monoxide tcr
the lithium enolate of a,o-diphenyiacetophenone
t17);
a second, dominating at -78o, involves 3 equiv of
phenyllithium and 3 equiv of' carbon monoxide and
generatesthe trilithium trianion 72. The products of
the reaction isolated following quenching with water or
acetic anhydride are derived in straigtrtforwarci ways
from 11 and22. The mechanism implied by these data
is summarized in SchemeIII, together with specuiations
Reactrr:n
Scheme
II[. Summarizing
Sequence
fbr tl"re
Conversron
to Producis
of Phenyllithium
and CarbonN{r.rnoxide
(PhLi),
PhLi =*
\co
LiO--\^
Ph
."./
--ot-;
l : i
Ph't
ro
+
f!
lr
li
-.1 ici)
iti
?
! t l
Lr"-t'
iph
-r,'lr
Y
LUI
Ii
I
I
o\,..".-Fh
i
t
jllli
!
t\o
nnit
i
F'hi'ft( ii i
''1'
v
/'
Y
-z'u
'rl'
,,
-//
Lio oli
i-o
0Li
li
/
Phr.i i i i
+-PhzC-C:C
'zco I C
I
|
\
Ph
i
l i l \ t ' l! / /
I
/
-u.:ti
/ l
r\I:
o
lr
Pil
tti
tl
I t : i {l
C:g t\
ii LLi*
i*
!:{1.
/
i
Ph
Ph
Ph !
Ph_l
LPh
17
l9
I r \ l
Ph
|
Ph
I
l/ ' ' \ \
o
ll
l*,u
Y
OFi OH
bH,oH
PhrcH
Ph:c-cPh:
\0/[rl i
(, ]i
Ph,{.;-_i--'.
P
h-, { . ; - _ i'-rl.
Pir
I H.O
v-
Ha
t//
Ph- ,c
\ -c
J
oPh
\/
C-C
/\
I
I
l-r.
? 1,.,-
./l
F!
-1"-
o
1l
i"
i[l
ct)
l i
lf,i
l.
*
ti
-"
|
t)L,i
tl
Pir',C--Cf'h
p
' "l -, "t -;
.lI:1
IB
/ r,t:
t'
o
Phj
LPh
22
LiO
ii -
l i l
,
Ph
o
7
HO
\/
CH-C]
/\
Ph,C
and one another at rates that are comparable with or
faster than the initial rate of formation of dilithium
benzophenonedianion 18. In particular, our inability
to generatemore than traces (ca. I f) of benzhydroi on
hydrolysis of reactive mixtures that have absorbed only
small quantities of carbon monoxide indicates that the
concentration of 18 is never high and that its subsequent
reactions with carbon monoxide and phenyllithiurn (or
benzoyllithiurn, whichever is actually involved) are
faster than its formation. Further, sincethe particular
combinations of benzophenone dianion, carbon
rnonoxide, and phenyllithium shown in SchemeIII are
certainly not the only ones that can be written, the low
product yields observed under many conditions may
result i-rom condensations of these materials in diiferent combinations to yield higher molecuiar weight
products" The factors influencing the partitioning of
intermeciiatesbetween the reaction paths so far identtfieci have not been established. One attempt to test
the hypothesis that the relative importance of the lowand high-temperature paths for the reaction reflected
the concentration of carbon monoxide in solution by
studying the reaction at high carbon monoxide pressure
was f,rustratedby a drop in the prodtrct balance; further
studieshave not been carried out"
T'ire most important mechanistic question still unresolved concerning this reaction is the rmportance of
benzoyllithiurn in these transformations" Quaiitative
correiatron of' the reactivill, toward carbon rnonoxide
cri a nrrm"ner of" cirganolithium reagents with theii
basicitv is comoatible with, but does not demand, producti on oi transi t.ory acyl l i thi um compounds as t he
first intermediatein these reactions; the ptrausibilityot
thesemateriaisas intermediatesis increasedby previous
work in which thelr have also been implicate6[.e1'2'i
Nonetheless. tirere is no unambiguous methocl of'
distinguishing between,e.9., conversion o'i monomenc
phenyllithiurn to dilithium benzophenonedianion L8
b-v wav of benzovllithium and conversion of dimeric
phenvllithium to 18 by a concertedinsertion of carbon
monoxide into ari aggregate; similarly, there is presently
no way of deciding whether or not t.ransformationsof
18 to 22 or l7 involve benzoyllithium.
In a more generalvern"the reaction of organic anions
with carbon rnonoxidewould seemto hold promlse as a
method of generatrnga. number of unusual types of
organic anions--especialiydilittrium dianions of symmetrical ketones and possibly acyllithium reagentsprovided that ways can be devised to inhibit the condensation reactions that lead to formation of the
mechanistically significant but synthetically unappealing types of products encounteredin thesestudies.
Ph
Experimental Section
reagents
GeneralMethods. Reactionsinvolvingorganometallic
of
for manipulation
werecarriedout usingstandardtechniques
Melting points were
compounds.so
oxygen and water-sensitive
capillarymeltingpoint apusinga Ttromas-Hoover
determined
O
OH
8
concerningthe derivation of certain of the minor products and the structures of undetected intermediates between establishedstructures.
The complexity of this mechanism, and of the resulting product mixtures, suggeststhat many of the various
intermediates formed during the course of the reaction
take part in further reactions with carbon monoxide
paratus and are uncorrected. Boiling points are uncorrected.
Nmr spectra were run on Varian 4-60 or Varian T-60 spectrometers; chemical shifts are reported in pnm downfield from TMS and
coupling constants in Hz. Infrared spectra were taken in sodium
chloride cells using a Perkin-Elmer Model 2378 grating spectrophotometer" Llitraviolet spectra were determrned on a Cary 14
( 5 6 ) D . F . S h r i v e r ," T h e M a n i p u l a t i o n o f A i r - s e n s i t i v eC o m p o u n d s , "
M c G r a w - H i l l , N e w Y o r k , N . Y . , 1 9 6 9 ,C h a p t e r 7 .
Whitesides, et al. f Mechanism
of Reaction
of Carbon Monoxide
with Phenyllithium
8128
spectrophotometer. Mass spectrawere determinedon a HitachiPerkin-ElmerRMU-6f) or RMU-6E mass spectrometer. Glpc
analyses were performed on F & M Model gl0 instruments
ecluippedwith flameionizationdetectorsand Disc integrators. Analyticalthin-layerchromatography(tlc) wasperlbrmedusingBaker_
flex preparedanalyticalplatescoatedwith silicagel I B-F or 2B-F.
Preparativetlc plates were either Analtech plates precoated with
silicagel GF or home-madeplatescoatedwith Merci<silica gel pF254. Diethyl erherwas distilledfrom lithium aluminum hydrideor
calcium hydride under a nitrogen atmosphereimmediateiybefore
t-rse; 1,2-dimethoxyethane
(DME), tetrahydrofuran (THF), and
benzenewere purified by distillation under nitrogen from dark
purple solutions or suspensionsof disodium benzophenonedianion. Hexanewastreatedwith concentratedsuifuricicid, washed
with water, dried (caclz), and distilled from a suspensionof disodium benzophenone
dianion under nitrogen. carbon monoxide
(c. P., Matheson)wasroutinelypassedthrougha columnof calcium
sulfate before use. However, no significantchangesin product
yields were observedusing carbon monoxide pass.d over calcium
sulfate,passedthrough a solution of disodium benzophenonedianion in DME, or taken directly from the cylinder without treatment. Glpc analysesfor compoundst and2 werecarriedout using
an 8-ft column packedwith 5% DEGs on chromosorb w or a 2-f7
column packedwith 5 "fl Carbowax20M on gG-100meshchromosorb P using ,-alkanes as internal standards. Analysesof 3, 4,
and 5 were carriedout using a 2-ft column packed wiin s7 sE-30
on 80-100meshchromosorb P usingeicosaneas an internal standard. Analysesfor 10, ll,2s, and26 werecarriedout with eithera
4-ft or 8-ft columnpackedwith 3 %ov-17 on g0-100meshchromosorb Q using dotriacontaneas an internal standard. Benzhydrol
was analyzed on a 4-ft, 5/. carbowax 20M on chromosorb w
column usingoctacosaneas internal standard. phenyllithiumwas
preparedusingstandardprocedures;z-butyllithiumin hexanewas
purchased from the Foote Mineral corp. concentrations of
organolithium reagentswere determineduiing a double titration
method.s? organolithium reagentsolutionswere discardedwhen
the concentrationof residualbasein theseanalysesexceeded10%
of that organolithium reagent; however,residual base titer had
no obvious influence on product distributions. Microanalyses
wereperformedby Midwest Microlabs,Inc.
a,a-Diphenyl-a-hydroxyacetophenone
(4), preparedin lg ii yield
accordingto the procedureof Greeneand Zook, had mp g4-g5.
[it.5amp 84.5-85'].
a-Hydroxyacetophenone
(6), preparedin 30il yield by the pro_
cedureof Tsuji,sehad mp 84-85..
1,3,3-Triphenyl-1-propene(16). Benzyltriphenylphosphonium
chloride (4.3 g, 15 mmol) in 50 ml of ether was added fo a dry,
200-ml, three-neckedflask equippedwith a condenser,dropping
funnel, and nitrogen inlet tube. ,-Butyllithium (10 ml, t.S l,r, t5
mmol) was addedslowly to the vigorouslystirredsolution and the
resultingorangemixture was allowed to stir at 25ofor 3 hr. To
this solutionwasadded3.8g (20 mmol) of a,a-diphenylacetaldehyde
in ether. The resultingmixture was allowed to reflux overnight,
yieldingan almostcolorlesssolutionand a white precipitate. The
mixture was hydrolyzedand the white precipitate*u, i.pu.uted by
filtration and washedwith ether. The combinedether layer was
concentratedand passedthrough a silicagel G column (2 X g cm)
eluting with Z:1 hexane:methylene
chlorideto yield 0.g e Gg%)
of 1,3,3-triphenyl-1-propene
as a white crystallini solid haiing mp
93.5_-95.5'
[it.oo mp gg-gg.]: ir (cHCl,) :050, 2870,1600,1450,
970 (trans olefin) cm-'; nmr (CDC!) 6 7.2-7.4 (m, l5), 6.4_6.g
( m , 2 ) , a n d 4 . 9( d , 1 . J : 7 H z \ .
e (7) was prepared in lorv
, 1,3,3-Triphenyl-1,2-propanedion
yield by the procedureof Sharpless,et ctl.;30O.OO
g (2.44 mmol)
of I,3,3-tripher-ryl-I-propene
in 10ml of DME wasaddedslowlyto a
stirringsolutionof 1.58g (9.76mmol) of potassiumpermanganare
in l5 ml of 99.91[aceria
c n h y d r i d ek, e p t a t 0 ' b y i m m e r s i o nr n a n
ice bath. The solutionwasallowedto stir at 0'ior 1.5hr and was
then hydrolyzed and titrated witrr a saturated sodium bisulfite
solutionto destroyexcesspermanganate. Etherwasaddedancithe
solutionwas washedwith crz.l0 volumesof water,and three20-ml
portions of 10"1potassiumhydroxide. The ether was dried (MgSOo)and concentratedto yield a yellow oil. Isolationof the vellow
( 5 7 ) G . M . W h i t e s i d e s ,C . p . C a s e y , a n c l J . I ( . I ( r i e g e r ,
J. Amer.
Chem.Soc.,93, l31.g(l9i.l), end referenlescited therein.
( 5 8 ) J . L . G r e e n ea n d H . D . Z o o k , i b i d . , g O , 3 6 2(91 9 5 g ) .
( 5 9 ) T . T s u j i , T e t r a h e d r o nL e t t . , 2 4 1 3 ( 1 9 6 6 ) .
( 6 0 ) J . H . B u r c k h a l t e r z r n dS . F L J o h n s o n ,J r . , . 1 .A m e r .
Chent. Soc.,
7 3 , 4 8 3 0( 1 9 5 1
).
componentusing preparativetlc coated with 2 mm of silica gel pF254,using 2 : I methylenechloride : benzeneas an eluent afforded the
desiredproduct as an oil: ir (CHCIB)3030,2900,1715,1670,
1600,
1500.1450,1100cm-r; nmr (CDCla)6 7.1-8.0(m, l5), 6.0 (s, 1)j
massspectrum(70 eV) (rel intensity)300 (6.4, M+). 167 (36), 105
(100),77 G7); calcdmol wt for CzrHroOz
300.1150,
founcl300.1149.
Hydrolysis of 17 afforded 7 in better yield. A 50-ml roundbottomed flask equippedwith a Teflon-coatedmagneticstirring bar
and No-Air stopperwas chargedwith 0.77 g (5.5 mmol) of 2,i,6,6_
tetramethylpiperidine
and l5 ml of THF. The flaskwassweptwith
nitrogenand cooledto 0". Methyllithium (2.2 ml of a 2.4 N ether
solution, 5.2 mmol) was added to the solution by syringe. The reaction mixture was stirredfor 10 min, and a solution of 1.5g of 14
(5 mmol) in 25 ml of THF was acidedby cannula. The reiulting
deep red solution was stirred at 0o for 30 min and l0 ml of i
saturatedaqueoussolution of ammonium chloride was added by
syringe. After the reaction mixture had stirred for l0 min. an
additional 20 ml of water was added and stirring was continuedfor
an additional20 min. The layerswereseparated,the aqueouslayer
was extractedwith 30 ml of ether, and the organic layerswere combined, dried (NasSon),and concentratedby rotary evaporation.
The orangeoil remainingwas distilledthrough a short-paihstill to
yield I .I e Q.l mmol, 737i.)of I as a yellow oil, bp I 55. a0.l5 Torr).
The most convenientprocedurefor the preparation of 7 involved
hydrolysisof 11, isolatedfrom an aceticanhydridequenchof the
low temperaturereactionof phenyllithiumwith carbon monoxide.
Typically,a solution of 1.5g(4.4 mmol) of ll in 50 ml of methanol
was treated with 0.5 ml of concentratedhydrochloric acid. The
solutionwas allowedto reflux for 4 hr and was then saturatedwith
sodium chloride. The organicproductswere extractedwith three
30-ml portions of ether. The combinedether phasewas washed
with aqueoussodium bicarbonatesolution, witer, and aqueous
sodium chloride solurion,dried (MgSoq),and concentratedto give
g of a crude yellow oil. Compound 7 was isolatedtn AO%
1:3_3
yield from this oil by preparativetlc.
1,1,2-Triphenylethane-1,2-diol.
a,a-Diphenyl-a-hydroxyaceto_
phenone(0.28g,0.97mmol) in 3 ml of ethyletherwasaddedslowly
with stirringto lithium aluminumhydride(0.138g, 3.65mmol) in l5
ml of ethyl ether under nitrogen at room temperature. After 15
min, the reactionwas quenchedby the slow addition of ethyl acetate. Severalmilliliters of ethyl ether was added, followed by
severalmilliliters of water. The organic layer was separatedand
dried (Na2SO,). The solventwas removed,leavinga solid which
was recrystallizedfrom absoluteethanol giving 0.20 g (72%) of
1,1,2-triphenylethane-1,2-diol,
having mp 165-166. [lit.or mp
16 8 ' 1 .
1,2,2-Triphenyl-1-acetoxyethylene
(10) was prepared from 2 by
the methodof Houseand Trost62
in 65ft yield or in 52f yield by a
procedureanalogousto that describedfor 2s (except that LiTMp
was used in place of lithium diisopropylamide): mp 104-105.:
nmr (CClr) 6 7,2 (m, 15), and 1.85 (s, 3); ir (CCl.r)3030,2915,
1760, 7600,1500, I 440, 1360,1205,1I 70, 1050, 1020,7 30,6g0cm- r ;
massspectrum(70 ey) mle (rel intensity) 314 (16, M+), 273 (22),
272 (r0O),l6s (34), 105(29).
Anal. Calcd lbr CszHraOz:C, 84.05: H, 5.77. Found: C.
8 3 . 7 8 :H . 5 . 9 3 .
1,1,3-Triphenyl-2-acetoxy-prop-2-en-3-one
(11) was isolated as
the major product on quenchingthe mixture obtainedby reaction
betweenphenyllithiumand carbon monoxide at -70o with acetic
anhydride. An ether solution of 30 ml of phenyllithium(0.g05N,
25 mmol) was allowed to stir under an atmosphereof carbon
monoxideat -70" until reactionwas complete. Freshlydistilled
acetic anhydride(10.2 g, 100 mmol) was added by syringeto the
vigoror,rslystirring solution. The solvent was removed in uacuo
(1.0Torr) leavinga white solid which wasfilteredand recrystallized
from ethanolto give 1.34g(4877 of a whitecrystallinesolid,1,3,3triphenyl-2-acetoxy-2-propen-l-one
(fl):
mp 140.5-142"; ir
(CHCIB)3025,3010, 1755,1655m, 1600,1575,1500,1450,1375,
1 3 3 0 ,1 2 7 0 1
, 1 8 0 1, 1 5 0 1
, 0 2 0 , 9 8 0 , 9 5 0 , 8 8c 0m - r ; n m r ( C D C I 3 6)
7.0-7.95(m, 15),and2.l (s,3).
Arrul. Calcd for CzrHrgOa: C. 80.68; H. 5.30. Found: C,
8 O . 4 2H
: .5.44.
This materialwas also synthesizedby a route analogousto that
describedfor 26.
N-(1-Phenylethylidene)cyclohexylamine
(12) was preparedby the
( 6 1 ; g . A . G u t h r i e ,E . Y . S p e n c e r , a n d G . F . W r i g h t , C a n . J . C h e m . ,
35,873(1957).
(62) H. O. Houseand B. M. Trost, J. 0rg. Chem.,30, 1341 2502
,
( 1e 6 5 ) .
Journal of rhe American Chernical Society I 95:24 Nouember 2g. Ig73
I
8129
method of Norton.63 Acetophenone(18 g, 0.15 mol). 17.4 ml of
(15 g, 0.15mol), and l0 ml oi benzenewere placed
cyclohexylamine
in a 50-ml round-bottomed flask equippedwith a Dean-Starktrap,
reflux condenser,Teflon-coatedmagneticstirring bar, and outlet to
a bubbler. The apparatuswas swept with nitrogen and the reaction mixture refluxed for 16 hr with continuousremoval of water
and then concentratedat 12 Torr to remove all material boiling
below 98'. The pot residuewas distilledtrap-to-trapat I Torr to
yield 18 g of a clearliquid (90 mmol, 67%): nmr (CCl,')6 1.57(b'
l0), 1.87(s, 3), 3.47(b, l),7.30-7.67(m, 5). This materialwasnot
purified further.
(13) was preparedby a procedure
1,3,3-Triphenylprop-2-en-1-one
analogousto that describedbelow for 1-phenyl-3'3-di(lerl-butvlp h e n y l ) p r o p - 2 - e n - 1 - o nm
e :p 8 4 - 8 5 ' [ l i t . 0 a m p 8 G 8 7 " ] ; n m r
( C D C l a )6 7 . 1 3( s , l ) , 7 . 2 7 - 8 . 0(0m . 1 5 ) .
oxide (14) was preparedusingthe
1,1-Diphenyl-2-benzoylethylene
nmr
procedureof House:6t mp I l5-119' [lit.esmp 123.5-124.5'],
( C D C h )6 4 . 7 0( s , 1 ) . 7 . 2 3 - 8 . 0(0m , l 5 ) .
l-Bromo-4- tert-butylbenzene.In a 500-ml, three-necked.round
bottomedflaskequippedwith a Teflon-coatedmagneticstirring bar,
a refluxcondenser,addition funnel,and a gasoutlet tube connected
(0.75mol). The
to a bubblerwas placed100C of lert-butylbenzene
addition funnel was chargedwith 38.5ml of bromine (120 g' 0'75
mol). and the brominewasaddedto the stirredreactionmixtureat a
fairly rapid rate" Evolution of hydrogen bromide proceededfor
ca.2hr. at which time the reactionmixturewas irradiatedwith a
flood lamp and was stirred for an additional 48 hr. The red reaction mixture was washedwith 100 ml of 10f aqueoussodium bisulfitesolution, 100ml of water, 100ml of l0i4 aqueoussodiumbicarbonatesolution.and an additional100ml of water. The cloudy
yellow organicliquid was dissolvedin 300 ml of ether, dried (MgSOr),and concentratedand the resultingiiquid distilledat aspirator
vacuum to yield 90 g of product (0"42 mol, 56",;): bp 108" (14
(q.4i.
Torr), lit.66bp 230o,nmr (CClr)6 1.42(s,9), 7.0-1
(23). The procedureusedfor the
4,4'-Di-tert-butylbenzophenone
preparationof 23 was modeledon that describedb1' Jorgenson.6T
ln a flame-dried. 500-ml. three-necked,round-bottomed flask
magneticsttrring bar, a rellux conequippedwith a Teflon-coateci
denser,an addition funnel,and No-Air stopperswas placedI '5 g of
freshl.v
iithium hydride (0.19 mol) and 50 ml of dimethoxyethane,
distilled from sodium benzophenoneketyl. The reaction vessel
wassweptwith nitrogen,and a solutionof 20 g of 4'tert-bstylbenzoic
was
acid (0.11 mol) in 80 ml of freshly distilled dimethoxyethane
added through the addition funnel. After addition was complete,
the reaction mixture was refluxedfor 6 hr, then cooled. To the
cooled (0") slurry of lithium carboxylatewas added slowly by
in
cannula 110 ml of a 1.14N solutionof 4-tert-butylphenyllithium
usingunether,in turn preparedfrom 1-bromo'4-tert-butylbenzene
exceptionalprocedures. Most of the solid materiaipresentin the
reactionmixture dissolvedin the courseof the addition. After all
the lithium reagent had been added. the reaction mixture was
stirred for I hr at room temperature,and was then quenchedby
transferringthe solution lry cannulato a well-stirredsolution of ice
water (500 ml) in a 1-1.erlenmeyerflask. The organic layer was
separated,washed with two 100-ml portions of I A sodium
and concentratedon a rotary
hydroxide solution, dried (MgSO-a),
evaporator to yield a white crystallinesolid. which on recrystallization from hexane gave 26.Ag of 23 (0.88 mol, 79o,,;)t mp 1321 3 3 ' ; n m r ( C C l o )6 1 . 3 7( s . l 8 ) , 7 . 4 3( q , 8 ) ; i r ( C C l 4 )1 6 7 5c m - t
(C:O).
Anal.. Calcd for
85.44; H, 8.92.
Benzylmagnesiumchloride was prepared using a modified version
of the procedure described by Adkins and Zartman.6s In a 250-ml,
three-necked, round-bottomed flask equipped with a Teflon-coated
, magnetic stirring bar, reflux condenser, and No-Air stoppers was
placed 2.0 g of magnesium turnings and 100 ml of freshly distilled
ether. Benzyl chloride (10 g,79 mmol) was added to the wellstirred mixture by syringe; the benzyl chloride was added in I ml
portions at the beginning of the reaction; once the reaction had
( 6 3 ) D . G . N o r t o n , e t q l . ,J . O r g . C h e m .1 9 ' 1 0 5 4( 1 9 5 4 ) .
( 6 4 ) P . L . S o u t h w i c k , L . A . P u r s g l o v e ,a n d P . N u m e r o f , J . A n t e r .
C h e m .S o c . ,7 2 , 1 6 0 0( 1 9 5 0 ) .
( 6 5 ) H . O . H o u s ea n d D . J . R e i f , i b i d . , 7 7 , 6 5 2 5( 1 9 5 5 ) .
(66) C. S. Marvel, M. B. Mueller, C. M. Himel, and J. F. I(aplan,
ibid.,6l,277t (1939).
( 6 7 ) M . J . J o r g e n s o nO
, 8 ,I ( 1 9 7 0 ) .
, r g .R e a c t . 1
(68) H. Adkins and W. Zartman, "Organic Syntheses,"Collcct. Vol,
I I , W i l e y , N e w Y o r k , N . Y . , 1 9 4 3 , p6 A 6 .
initiated, it was added at such a rate that refluxing was maintained
at a steadylevel. The pale green solution was stirred 1 additional
hr and then transferredby cannula to a flame-dried storageflask.
as an indicaTitration against2-butanol,using 1.10-phenanthroline
tor,6eyieldeda valueof 0.67 M for the 105ml of benzylmagnesium
chloride solution (ca. 89%).
(31) was synthesized
l,l-Di($-t e rr-butylphenyl)-2-phenylethanol
by a procedureanalogousto that describedby Adkins and Zartchloman.6E To a solutionof 105ml of C.67M benzylmagnesium
round-bottomed
ride in ether (70 mmol) in a 250-ml.three-necked.
flask equippedwith a Teffon-coatedmagneticstirring bar, a reflux
condenser,and No-Air stopperswas addedby cannulaa solutionof
20.6e of 23 (70 mmol) in 100 ml of ether. Each drop of ketone
turned a deeppurple as it struck the solution of Grignard reagent,
the color faded with stirring. After addition was complete.the reaction mixture was stirred for an additional 0.5 hr. The solution
was transferredby cannula to 50 ml of stirred ice water. To the resulting slurry was added 35 ml of cold 2O'l sulfuric acid. The
organiclayer was separated.the aqueouslayer extractedwith two
50-ml portions of ether, and the organic layers combined, dried
(MgSOr), and concentratedto yield 25.5 e O4%) of crude 3l:
mp 109-ll0' after recrystallizationfrom hexane; nmr (CCl4) 6
1. 2 3( s ,1 8 ) ,1 . 9 3( s .2 ) ,3 . 4 0( s , 1 ) ,6 . 7 2 - 7. O Z( m , 5 ) ,7 . 1 7( s ' 8 ) .
Anal. Calcd for CzrHarO: C, 87.04; H, 8.80. Found: C,
8 6 . 9 8 ;H , 9 . 0 6 .
(32) was prepared by
l,l -Di(4-t e rr-butyI phenyl)-2-phenylethylene
thionyl chloride-pyridinedehydration of 31 according to a proceduremodeled on that of Newman.?o In a 250-ml erlenmeyer
flask equipped with a Teflon-coatedmagnetic stirring bar was
placed25.5g (66 mmol) of crude31 and 150ml of pyridine.freshlv
distilledfrom barium oxide. The reactionmixture was sweptwith
rritrogen,and the ffaskcappedwith a No-Air stopperand cooledin
an ice bath. Thionyl chloride(10 g, 80 mmol) was addedslowly
to the stirreclmtxture lry syringe. The mixture was stirred for 1
hr, poured into 400 ml of water. and extractedwith three 50-ml
portlonso! ether. The combirredetherextractswerewashedwith
three50-ml portionsol' 10"; aqueoushydrochloricacid and three
50-mlportionsof water. The organicmaterialwasdried(MgSOr)
20.5g (849il of crude32 as a paleyellow
to 1uig16
and concentrated
from hexaneyieldedlargewhite crystals:
solid. Recrystallizatton
r n p7 8 - 8 1 ' ; n m r ( C C i i )6 1 . 2 1( s .9 ) . 6 . 7 2 - 7 . 2( r3n .l 4 ) .
Anal. Calcd for CzsH:r:l C. 91.30; H, 8.69. Found: Cl.
91.14 H, 8.76.
I -ol (3f i.
1- Phenyl-2,2- di(d-t ert -butylphenyl)-2-acetoxyethan(irude 32 (20.5 g. 56 mmol), 125 ml of chloroform,and 0.5 g of
sodium acetatetrihydratewere placedin a 250-mlerlenmeyerflask
with a Teflon-coatedmagnetic stirring bar. The mixture was
cooledin an ice bath.stirred.and 7.4 ml of 10il peraceticacid (56
rnmol) was added" The rce bath was removed after t hr: the
mixture was stirred for 60 hr, poured into 200 ml of ice water"and
extractedwith two 50-ml portions of chloroform' The combined
organic layers were washedwith 50 ml of 1073aqueoussodium
carbonateand two 50-ml portions of water. The organicsolution
to yielda gumm)'whitesolid.
wasdried(MgSOr)and concentrated
of 33: mp 203from hexaneyielded12.2g (4972,'S
Recrystallization
2 0 - 5 ' ; n m r ( C C l r ) 3 1 . 2 3( s . 9 ) , i . 3 5 ( s , 9 ) . 2 . 4 8 ( s , l ) , 7 . 0 0( s ' 8 ) '
7 . 3 3( s , 5 ) t i r ( C C l i ) 1 7 5 5c m - r ( C : O ) . T h i s s u b s t a n cwe a su s e d
without further purificationin the followingstep.
(34). A solutionof 10.2g
a,orDi(4-tert-butylphenyl)acetophenone
was placed in a
of 33 in 50 ml of dry hexamethylphosphoramide
100-mlround-bottomedflask equippedwith a Teflon-coatedmagnettc stirring bar and reflux condenserwith an outlet to a nitrogen
bubbier. The mixture was flushedwith nitrogen,then stirred and
heatedat 210' for 3 hr. The deep red solution was cooled and
poured into 400 ml of stirred ice water. The yellow solid whichr
precipitatedwas isolatedby suctionfiltration' This solid was dissolvedin 200 ml of chloroform; the chloroformextractedoncewith
100ml of water, dried (MgSOr),and concentratedto yield a yellow
solid, which on recrystallizationfrom hexaneyielded6.6 e Qa%)
o f 3 4 a s w h i t e n e e d l e s : m p 1 5 3 - . 1 5 4 ' n; m r ( C C l 4 )6 1 . 2 3( s , 1 8 ) ,
(Q:Q).
(m, I 3); ir (CClr)1700srn-1
5.77(s,l ), 6.90-8.01
Anal. Calcd for CrsHnO: C. 87.50; H, 8.33' Found: C,
8 7. 2 1 ; H " 8 . 4 6 .
1-Acetoxy- I -phenyl-2,2- di(4-t er t -butylphenyl)ethvlene (25).
(1.2 ml,0.8 g, 8 mmol) and 20
Freshlydistilleddiisopropylamine
( 6 9 ) S . C . W a t s o n a n d J . F . E a s t h a m , J .O r g a n o m e t c tCl 'h e m . , 9 ,1 6 5
(1967).
( 7 0 ) M . S . N e w m a r r ,A . A r k e l l , a n d T . F u k u n a g a , J ' A n t e r ' C h e m .
9 o c . , 8 2 , 2 4 9 8( 1 9 6 0 ) .
Whitesides,et al. I Mechanism o.l'Reaction of Carbon Monoxide with Phenyllithium
8130
ml of ether were placedin a flame-dried,125-ml,round-bottomed
flask equipped with a Teflon-coatedmagnetic stirring bar and
No-Air stopper. The flask was sweptwith nitrogenand cooledin
an ice bath and 5.0 ml of a 1.6M solutionof methyllithiumin ether
was added by syringe. The mixture was stirred for 10 min, and a
suspension
of 3.1 I (8 mmol) of 34 in 50 ml of ether was addedby
cannula. The solutionturned a deepyellow,and stirring was continued for l0 min. The resultingenolate solution was added by
cannulato a stirred solution of 5 ml of freshly distilledaceticanhydridein 100 ml of ether in 250-ml,round-bottomedflask. This
solution was treatedwith 100 ml of saturatedaqueoussodium bicarbonate. The organiclayer was separated,dried (MgSOr), and
concentratedto yield a yellow oil which solidifiedon standingovernight. This materialwastakenup in hot hexaneand recrystallized.
Unreacted ketone precipitatedfirst; crystallizationof the concentratedmother liquor yielded L0 g (28%) of 25: mp 144-146";
n m r ( C C l r ) 6 1 . 2 3( s , 9 ) , 1 . 3 3( s , 9 ) , 1 . 8 0( s , 3 ) , 6 . 8 7 - 7 . 2 (3m , 1 3 ) ;
ir (CClq) 1745cm-t (C:O).
Anal. Calcd for CsoHsaOr:C, 84.50; H, 7.98. Found: C,
84.25; H, 8.28.
N-(1-Phenyl-3,3-di(4-terr-butylphenyl)-3-hydroxy)propylidenecyclohexylamine(35) was synthesizedby a directedAldol condensation using a proceduresimilar to those describedby Wittig and
f{s55s.2e'7tFreshly distilled diisopropylamine(5.05 g, 50 mmol)
and 40 ml of freshlydistilledTHF wereplacedin a flame-dried,300ml, round-bottomedflask equippedwith a Teffon-coatedmagnetic
stirring bar and No-Air stopper. The reaction vesselwas flushed
with nitrogen and cooled to 0o, and 30 ml of a 1.6 M solution of
methyllithium in ether was added by cannula. Evolution of
methanewas evidentduring the addition. The mixture was stirred
for 10 min, and a solutionof 10 g (50 mmol) of 12 in 80 ml of THF
was added by cannula. This yellow solution was stirred at 0" for
l0 min, cooledto -78o, and a solutionof 15.1g (50 mmol) of 23
in 80 ml of THF was added by cannula to the stirred solution.
After addition wascomplete,the coolingbath wasremovedand the
mixture was allowed to stand for 20 hr; it was then cooled to 0"
and treated with 100 ml of water. Stirring was continued at 0o
for 0.5 hr. The cold mixture was filtered to yield the ketimine 35
asa white solid. The filtratewasdilutedwith 50 ml of etherand the
organiclayer was separated,dried (MgSOr), and concentratedby
rotary evaporation to yield additional product. The combined
crude product was usedwithout further purificationor analysisin
conversionto 36.
l,l-Di(4-terr-butylphenyl)-3-phenylprop-1-en-3-one(36).
The
hydrolysisof the crude ketimine 35 was carried out by a method
analogou.s
to that of Reiff.2e In a 500-ml, round-bottomedflask
equipped with a reflux condenser and Teflon-coated magnetic
stirring bar was placed the total quantity of crude ketimine described above and 250 ml of 2 N sulfuric acid. This mixture was
heatedat reflux temperaturefor 2 hr. The cooled reaction mixture
was extractedwith two 100-mlportions of ether. The ether extracts were combined,dried (MgSOe),and concentratedto yield a
yellow oil. Analysis of this yellow oil by nmr and tlc indicated
that it was a mixture of a,B-unsaturatedketone and p-hydroxy
ketone. This crude oil was then dissolvedin 150ml of ethanoland
treatedwith 15 ml of concentratedhydrochloricacid at reffux for
4 hr. The reactionmixturewascooledand extractedwith two 100ml portions of methylenechloride. The organic portions were
combined,washedwith 100 ml of saturatedaqueoussodium bicarbonate,100 ml of water, dried (MgSOa),and concentratedto
yield a yellow solid. Recrystallizationfrom ethanol afforded 5.4
g (28%) of product. Treatmentof the mother liquors with additional hydrochloric acid, followed by further recrystallization,
yieldedan additional 3.6 g of product; the total yield of 36 was 9.0
e g 6 % ) : m p 1 0 4 - 1 0 6 on; m r ( C C l +d) 1 . 3 0( s , 9 ) ,1 . 3 7( s , 9 ) ,7 . 0 3 ) 6 7 0c m - 1( C - O ) .
7 . 8 7( m , 1 4 ) ; i r ( C C l 1 1
Anal. Calcd for CzsHezO:C, 87.87; H, 8.08. Found: C,
8 7 . 9 8 :H . 8 . 2 2 .
l,l-Di(4-terr-butylphenyl)-2-benzoylethylene
oxide (37) was prepared by epoxidationof 36 by a proceduremodeled on that describedby Houseand Reif.65 In a l-1.erlenmeyerffaskequipped
with a Teflon-coatedmagneticstirring bar was placed 3.96 g (10
mmol) of a,B-unsaturated
ketone36 in 300ml of absolutemethanol
and 50 ml of methylenechloride. To the stirredsolutionwasadded
6 ml of 6 iV aqueoussodium hydroxideand 12 ml of 30f hydrogen
peroxide. This mixture was stirred for 36 hr; additional 9-ml
portionsof 30'/" hydrogenperoxidewereaddedat 6, 10,and 24 hr.
After 36 hr, the reactionmixturewasfilteredto yield 3.5g of a white
( 7 1 ) G . W i t t i g a n d A . H e s s eO
, r g . 5 y n . , 5 0 , 6 6( 1 9 7 0 ) .
solid. The filtrate was treatedwith an additional 9 ml of hydrogen
peroxide,stirred another 12 hr, treated once again with 9 ml of
hydrogenperoxide,stirred a final 12hr, and then filtered to yield an
additional0.8 g of white solid. The solid materialwas combined
and treated with 100 ml of ether. The insoluble solid remaining
was removed by suction filtration; the filtrate was concentratedby
rotary evaporationto yield 2.32 g (5671 of 37: mp 149-151';
) 1 . 2 7( s , 9 ) ,1 . 3 5( s ,9 ) , 4 . 3 5( s , 1 ) , 7 . 3 0( m , 1 3 ) ; i r ( C C l q )
n m r ( C C l . r6
1700cm_r (C:O).
Anal. Calcd for CrsHezOz:C,81.46; H,7.76. Found: C,
8 4 . 3 9 :H . 7 . 9 0 .
phenylprop-1-en-3-one
l,l-Di(4- t erl-butylphenyl)-2-acetoxy-3(26). Freshly distilledTHF (20 ml) and 2,2,6,6-tetramethylpiperidine (0.,12g, 3 mmol) were placedin a flame-dried100-ml,roundbottomedflask equippedwith a Teflon-coatedmagneticstirring bar
and No-Air stopper. This mixture was swept with nitrogen and
cooledto 0". A solution of methyllithiumin ether (1.8 ml of a
1.6 M solution)was addedby syringeto the stirred mixture. Stirring was continuedfor 5 min, and'a solutionof 1.05g of the substitutedethyleneoxide preparedin the precedingstep in 20 ml of
THF was added by cannula. The deepred reaction mixture was
stirred for I hr at 0" and t hr at 25o and was then quenchedby
addition to a stirred solution of l0 ml of aceticanhydridein 75 ml
of ether. The resulting suspensionwas treated with 100 ml of
saturatedaqueoussodium bicarbonatesolution and the organic
layer was separated,dried (MgSOn),and concentratedto give an
orangeoil. This oil was distilledtrap-to-trapat I Torr to remove
the last tracesof aceticanhydrideand 2,2,6,6-tetramethylpiperidine.
The orange solid remaining was recrystallizedfrom ethanol to
yield 0.75 8((571 of 26: mp 168-169o;nmr (CCl4)6 1.13(s, 9),
1 . 3 8( s ,9 ) , 2 . 1 3( s ,3 ) ,6 . 8 7( m , 1 3 ) ; i r ( C C l r )1 7 6 0a n d 1 6 7 5c m - r .
Anal. Calcdfor CnHarOa: C, 81.93; H,7.49. Found: C,
8 1 . 8 9 ;H , 7 . 6 2 .
(9.7 g, 50
a,a-Diphenyl-p-ethylacetophenone.
DiphenylketeneT2
mmol) in 30 ml of ethyl ether was added slowly to a solution of
p-ethylphenyllithium(75.0 mmol) in 120 ml of ether at room temperaturewith vigorousstirring. After the addition was complete,
the reaction mixture was held at reflux temperaturefor 30 min,
cooledto 0 o,and hydrolyzedwith 20 ml of a saturatedaqueoussolution of ammonium chloride. Water (30 ml) was added and the
ether layer was separated. The aqueouslayer was extractedwith
two 100-ml portions of ether. The etherealportions were combined, washedwith water, and dried (CaClz). The ether was removed, leaving a solid which was dissolvedin absoluteethanol,
treatedwith decolorizingcharcoal,and recrystallizedto give 1.57g
(10.5%) of white crystals: mp 102-103"; ir (CClr) 1690cm-r
(C:O); nmr (CCln)6 7.17(m,14, aryl-H),5.88(s, 1, CH), 2.50(q,
2 , J : 8 H z , C H z ) ,a n d l . 2 2 ( t , 3 , J : 8 H z , C H s ) .
Anal. Calcd for CzzHroO:C, 87.96; H, 6.71. Found: C,
8 7 . 9 1 ;H , 6 . 7 4 .
(38). To a solution
3,3-Dimethyl-1-phenyl-2-hydroxy-1-butanone
of 3 g (15 mmol) of 2-phenyl-1,3-dithiacyclohexane
in 100ml of dry
tetrahydrofuran
cooledto -60" wasslowlyaddedl0 ml (15 mmol,
1.5N) of n-butyllithiumby syringe.TaTbe solution was allowedto
stir at -60" for I hr; then 1.6 g(17.5 mmol) of 2,2-dimethylpropanal was slowly added and the solution was allowed to warm to
-28" over a 4-hr period. The solution was hydrolyzedand the
organic layer was separatedand washed with aqueous sodium
chloride solution,dried (NarSO,r),and concentratedto give 3.5g of
a mixture of the startingthioketal and anothercompound. Without further purification,the 3.5g of white solid was addedto a 500flaskcontaining200 ml of 9:1 methanol:water
ml, round-bottomed
and 3.24g (15 mmcl) of mercuricoxide. The mixture was heated
to reflux undernitrogen; then 8.13g (30 mmol) of mercuricchloride
in 40 ml of the samesolventwas added. The mixture was allowed
to reflux under nitrogen for 4 hr. The resultingwhite precipitate
was separatedby filtration and washedwith three50-ml portionsof
methylenechloride. The filtrate was diluted with an equal volume
of water and extracted with three 50-ml portions of methylene
chloride. The combinedmethylenechloridephasewaswashedwith
water, aqueousammoniumacetate,and water,dried (MgSO.r),and
concentratedto give an cil which was a mixture of benzaldehyde
and anothercompound. The oil in ca. 100 ml of methylenechloride and a few drops of absoluteethanolwas allowed to stir overnight with 3.5 g of pulverizedcalcium chloride.TaThe calcium
( 7 2 ) U . S t a u d i n g e rC, h e m B
. e r . , 4 4 , 1 6 1(91 9 1 1 ) .
( 7 3 ) D . S e c b a c h ,S y r t t h e s i s1, 7 ( 1 9 6 9 ) .
( 7 4 ) I s o l a t i o n o f 3 7 b y a d s o r p t i o no n c a l c i u m c h l o r i d c w a s s u g g e s t e d
t o u s b y P r o f e s s o rB a r r y S h a r p l e s s .
Journal oJ'the American Chemical Society I 95:24 I Nouentber 28, 1973
8 13 1
0.313on silicagel 2B-F analyticalplatesusing4:1 methylenechlochloride was separatedby filtration and washedwith small portions
ride:etheras eluent. This compound(6), identifiedas a-hydroxyof methylenechloride and then was added to a mixture of 100 ml
was isolated from a 2O X 20-cm preparative tlc
acetophenone,se
of water and 100ml of benzene. The benzenelayer was separated,
plate coated with 2 mm of silica gel PF-254using 2: I methylene
washedwith aqueoussodium chloride, dried (MgSOo),and concentratedto give0.9 g (lZ %) of 3,3-dimethyl-1-phenyl-2-hydroxy-1- chloride:ethereluent, as a white crystalline solid: mp 84-85'';
from the
mmp 84-85". The ir spectrumof 6 is indistinguishable
butanone: mp 33-33.5'; ir (CClr) 3500,1570,1600'cm-r; nmr
publishedir spectrumof a-hydroxyacetophenone'76
( C C l n )6 7 . 2 5 - 7 .(9m , 5 ) , 4 . 6 8( d , l , . I : 8 H z ) , 3 . 3( d , l , J : 8 H z ) "
A secondcomponent appearedas a yellow spot having Rr 0.79
0.85(s, 9).
on analytical tlc silica gel 2B-F plates using methylenechloride:
Ana!" Calcd for CrzHreOz:
benzenein the ratio of 4: i as an eluent. To isolatethis substance.
74.97:'H, 8.40.
which was a minor product, an aliquot of the reaction mixture was
To a solution of 0.558
1-Phenyl-3,3-dimethyl-1,2-butanedione.
leavinga residsublimed(70', 0.05Torr) to removebenzophenone,
g (3.14 mmol) of l/-bromosuccinimidein 60 ml of 90f aqueous
acetonewas added 100 mg (0.522mmol) of 1-phenyl-3,3-dimethyl- ual yellow oil, enrichedwith this yellow substance,which was suhjected to preparative tlc From a 20 X 20-cm plate coated with
2-hydroxy-l-butanone in 20 ml of acetone. The solution was
2 mm of silica gel PF-254"elutingwith 2 :1 methylenechloride: benallowedto stir for 2 hr at 25' then diluted with 30 ml of I :1 methzene, was isolated a yellow oil (7), which gave only one spot by
ylene chloride:pentaneand 30 ml of saturatedsodiumbicarbonate.
analytical tlc using 4:l methylenechloride:benzeneas eluent.
The organic layer was washedwith live 30-ml portions of saturated
This substancehad ir spectrum. mass spectrum, and R; value
sodium bicarbonate.with saturatedsodium chloride. dried (Mgfrom that of an
SOr), and concentrated,yielding 0.79 g (80%) of 1-phenyl-3,3-di" (methylenechloride:benzene4: 1) indistinguishable
authentiesampleof 1,3,3-triphenyl-1,Z-propanedione.
methyl-l,2-butanedioneas a yellow oii. The oil can be purified by
f'he Rr value for a third compound (8) was A"47on analytical
preparativethin-layerchromatographyusing 6 : 1 cyclohexane:ethyl
silica gel 2B-F tlc plates using 3:1:12 benzene:ether:methylene
acetateas eluent. This substancehas nmr (CCln)6 7.3-8.0(m, 5,
chloride as eluent" The samesolventsystemwas usedwith 20 x
cffi-1,with n<t
1725,1695
aromatic),1.3(s,9, C(CH3)a),and ir (C.lCl4)
20-cmplatescoatedwith 2 mm of silicagel PF-254to isolatea colorOH absorption.
less
oil which solidifiedto a white crystallinesolid (8): mp 93.0Monoxide.
with
Carbon
Phenyllithium
Reactions
of
Small-Scale
94.A"; ir (CHCir) 3590,3500(br), 3050,28CI, i710, (C:C), 1600.
A stock solution of phenyllithiumwas preparedby adding appro1 5 0 0 .1 4 5 0 ,1 3 8 0c m - ' ; n m r ( C D C I 3 )6 7 . 1 - 7 . 4( m , 1 5 ) .5 . 6( s , l ) "
priate quantities of n-heptane.,l-tetradecane,and n-nonadecaneas
3.8 (broad s. l). and 3.12(s, 1); massspectrum(70 eV) nie (rel
internalglpc standardsto a solutionof phenyllithiumin ether. The
intensity)183Q4),182 (18),105(100),77 (65i.
resultingsolution was assayedbv double titration, and aliquots were
Anuf. Calcd ibr CnHrsOs: C, 79.22: H, 5.70. Found: C,
used for reaction with carbon monoxide. Typically, i5 ml of art
79.46:'H, 5.68.
ca. 0.5 l/ solution of phenyllithium was transferred either to a
Product Balanceby Isotopic Dilution. An ethereal solution of
Schlenk tube containing a Teffon-coveredstirring bar and con(31 ml, 0.52 N. l6 mmol), preparedfrom bromophenyllithium-d;77
nected to a gas adsorption apparatus or to a 40-ml heavy walled
and lithium wire, was allowed to stir under carbon
benzene-r/,?8
centrifugetube with stirring bar capped with a No-Air stopper,
monoxideat -70" untii reactionwas complete. T'hesolutionwas
The stirred solutions were exposedto carbon monoxtde (in the
quenchedwith saturaledaqueousammoniumchloridesolutionand
former casefrom the gasabsorptionapparatus,in the latter front a
concentratedhydrochloric acid. To the resulting mixture was
to the centrifugetutrethrough
carbon monoxidecylinderconnecteci
added authentic benzophenone(187 mg, 1.03 mmol), 6 (53 mg"
a length of Tygon tubing and hypodermicneedle). When gas atr0"39mmol),7 (13 *g,0.0434 mmol), and 8 (20 m9,0.063mmol).
sorption had ceased(4 hr at 0" and 1 atm pressure,2-3 hr at 0" and
The
organiciaver wasseparatedand washedwith water and aqueous
quenched
bvwas
mixture
reaction
dark
brown
2 atm)" the resulting
socjiumchloride solution' clried(MgSOn),and concentratedto an
the addition of 0.5 ml of'distilted water. Saturatedaqueousam6. 7, and 8 were isolatedfrom this
oil. Samplesof benzophenone,
monium chloridesolution(l ml) and ether(15 ml) wereadded,and
analysesusing preparativetlc" Benzooil for massspectroscopic
the ether layer was analyzedbl' gipc.
phenoneand 14 were isolatedusing Analtech tlc platesprecoated
Isolation and Characterizationof Products by Glpc. Benzophewith i.5 mnr of silicagel GF with 2:1 methylenechloride:cyclonone and benzil were identified by comparisonof glpc retention
hexaneeluent" The Rr valuesfor benzophenoneand 7 under these
times.massspectra.and rnfrareclspectraof coliectedsampleswitii
conditionsare 0.43 and 0"545.respectively. Using the same type
thoseof authenticsamples. Compouncis2 and 4 were isolatedb-v'
:ethereluent,6 and
of piate and I :2 : i methyienechioride: benzene
combining severalhydrolyzedreactionmixtures. The solventwas
8 wereisolated. Tire Rr yaluesfor 6 and 8 uncierthesetlc conditions
removedleaving a yellow oil which was dissolvedin a minimunl
ar:e0.40 and 0.514,respectively. Isotopicanalysesof eachof these
volurneof hot benzene^ The solutionwas allowedto cool to rootn
rsolatedisotoprcmixtureswerecarrledout usinga nominal ionizing
recrystaiand
were
collected
resulting
crystals
temperature,and the
(2):
voltageof l5 eV. In eachcase,the ratios reportedare the average
lized from absoluteethanol to give ct.a-diphenylacetophenone
-'(C--:Cl);
the ratio ol peak heightsoi
oi'severalspectra For benzophenone
mp 137.5-138"5
i l "i 1 . zm
s p 1 3 7 - . 1 3 9 ' lilr ( C C l 4 )1 6 9 5c r r '
the l92ll83 ions was 1"94+, 0.03. For 6 the ratio of peak heights
(m, 15;; massspectrum(70 ev)
nmr (CCln)6 5'86(s, 1), 7.17--8.(n
ions was 4.33 + 0.0-5. hor 7 the ratio of the peak
of the 1101105
mle(relintensityi272(2.4.M*), 167(30).105(100),'!7(14).
and the l10i 105ions was 8.2 + 0.1" For I
herghtsr:f the 177!167
C, 8t1.20; H, 5.92. Found: C.
Ana!. Calcd for C-zoH.roO:
the ratio of the peak heightsof the I 10/105ions was 33 -t 0.6.
8 8 . 1 2H
, , 5.95.
The product yieldsderivedfrorn thesedata are outlined in Table i.
a,a-Diphenyl-a-hydroxyacetophenone(4) was identified in the
Partial Reactionof Phenyllithiumand Carbon Monoxide in Ether
glpc
two
times
on
retention
hexanesolution by comparisonof its
and Quenchwith SodiumDeuteroxide. A solutionof phenyllithium
columns(8-ft 5% DEGS on ChromosorbW at 200oand 8-ft 139;
by synngeto a 25rn ether(5 ml, 1.0 M,5 mmol) was transferrecl
SE-52"on silanizedChromosorhW at 225') and its tlc rti valueson
ml. round-bottomedflask equipped with a No-Air stopper anC
two adsorbents(silica Gel and Alumina eluting with chloroT'eflon-coatedmagnetic stirring bar. This reaction mrxture was
form:methylenechloride 4:1) with those of an authenticsample.
sweprout with a streamof carbonmonoxideand then stirred under
Benzpincol(5) was assayedby treatingan aliquot of the original rean atmosphereof carbon monoxide for ca. 20 min. The reaction
action mixture with saturatedaqueousammonium chloriciesolumixture was cooledin an ice bath and 5 ml of sodium deuteroxide
tion, followed by hydrochloricacid and aceticacid, and analyzing
in degasseddeuteriumoxide (preparedby the addition of 0.i g of
the resultingsolution for benzpinacoloneby glpc.
sodium to 20 ml of deuterium oxide) was added cautiously by
Isolation and Characterizationof Products Using Preparative
syringe. The quenchedreaction mixture was aliowed to stir for
Thin-Layer Chromatography. Phenyllithium(50 ml, 0.6 li, 30.0
cla.30 min and was then diluted with 50 ml of water and 50 ml of
monoxide
atmosphere
mmol) was allowed to stir under a carbon
ether. The ether layer was separated,washedwith two 50-ml porat -70" for 6 hr. The resulting green reaction mixture was
quenchedwith 2 ml of saturatedaqueousammoniumchloridesolution and 0.25 ml of concentratedhydrochlonc acid. The ether
(76) "The Sadtler Standard Spectra," Sadtler RcsearchLaboratories,
layer was separated.dried (MgSOa),and concentrated,yielding
P h i l a d e l p h i a ,P a . , 1 9 7 0 ,i r p r i s m s p e c t r u m9 7 7 0 .
a viscousyellow oil" This oil was subjectedto thin-layerchroma(7?) An aliquot of phenyl-dr-lithium was quenched with water;
tography (tlc). The major unidentifiedspot had an Ri value of
columu
(75) A. C. Cope, P. A. Trumbull, and E. R. Trumbell. J. Amer.
C h e m .S o c . ,8 0 , 2 8 4 4( 19 5 8 ) .
the resulting benzene, collected from atr 9-ft 20% UC-W98
and analyzed by mass spectroscopy,was found to be 97.3 f( benzenedt 2.7 7, benzene-dr.
( 7 8 ) G . M . W h i t e s i d e sa n d W . J . E h m a n n , J . A m e r ' C h e m . 9 o c . , 9 2 ,
5 6 2 5( 1 9 7 0 ) .
Whitesides, et al. I Mechanism of Reaetion of Carbon Monoxide witlt Phenyllithium
8132
tions of water, dried (MgSor), and analyzedusing a coupled glpc
through a serum cap into 0.1 N solutions of phenyllithiumconmassspectrometer.
lained in 1-cm Pyrex spectrophotometercells. solutions of tritylReaction of Phenyllithium and carbon Monoxide in Ether and
lithium and of 17 were prepared by analogousproceduresstarting
Treatment of the ResultingReactionMixture with Lithium Aluminum
with tripheni,lmethane
and 10, respectively. Samplesof dilithium
Hvdride. A solution of 14 ml of 0.6 N phenyllithium(g.4 mmol)
benzophenonewere prepared by addition of small amounts of lg
in ether and0.27g(0.975 mmol) of eicosanein a flame-dried40-ml
to 0.1 N solutionsof phenyllithiumcontainedin l-cm pyrex cells.
centrifugetube, equippedwith a No-Air stopper ancl a magnetic
Samplescf 20 were preparedby reducingT4 mg of l-phenyl-3,3stirring bar, was allowed to stir at -7oo under an atmosphireof
dimethyl-1,2-butanedione
with excesslithium dispersionin 25 ml of
carbon monoxide for 4 hr. As usual, during the course of the
DME and diluting aliquots of this stock solution approximately
reactionthe solution first becamered and then green. when the
l:2.5 with DME. Solutionsof 15 wereobtainedby reactionof f .i
reaction was complete.one 1-ml aliquot was quenchedwith I ml
equiv of 37 with 1.0 equiv of LiTMp in ether, as describedin the
of aqueouspotassiumhydroxidesolutionand another l-ml aliquot
preparationof 26.
was quenchedwith I ml of saturatedammonium chloride solution
samplesused in studiesrequiring 18 or 19 in sorutionsfree of
and 0.1 ml of concentratedhydrochloricacid. The remainingrephenyllithiumwere obtainedby diluting concentratedsolutionsof
action mixture was added to a solution preparedby mixing 95 mg
thesesubstances
in closedsystemsusingstandardtechniques.a2
(2.5mmol) of lithi umaluminumhydride(LiAlH4) and20ml6f etherl
Experimentsinvolving the reactionof carbon monoxidewith lg,
refluxingfor 0.5 hr, and coolingto room temperature. The mixture
19, or phenyllithiumwerecarriedout by mixing the reactioncomwas allowedto stir at 25" under nitrogenfor 30 min and was then
ponentsdirectlyin the spectrophotometer
cell.
cautiouslyhydrolyzedwith 3 ml of water. Each of the hydrolyzed
Dilithium 4,4'-l)i(terl-butyl)benzophenoneDianion (24). In a
solutions were analyzedfor benzophenone,benzhydrol,and benzil
flame-dried,100-ml,round-bottomedflask equippedwith a Teflon_
by glpc. As controls, thesereactionswere repeatedusing 20 ml of
coatedmagneticstirring bar and a No-Air stopperwas placed0.93
phenyllithium(0.5 N,9.9 mmol) in ether. when each of the reg of 23 (3.2 mmol) and 60 ml of freshlydistilledether. The reacactionswas complete,a solution of 0.15 g (0.g3 mmor) of benzotion mixturewassweptwith argon,and 0.40g of freshlycut lithium
phenonein 5 ml of ether was added uia a cannulato each reaction
wire (57 mg-atoms)was added to the reactionflask in a streamof
mixture. The resultingmixtureswere hydrolyzedand treatedwith
argon. The flask was sealedwith a No-Air stopper and stirred
LiAIH{ as desciibedabbve. The hydroiyzed ether solutions were
overnight. The solution turned a deep blue, then purple, and
analyzedby glpc. Analysis of the glpc data indicated that the
finally dark red as the reactionprogressed
benzophenone
which had beenaddedprio rto treatmentwith LiAlHa
Using a syringe,20 ml of this red solution was withdrawn and
had beenreducedto benzhydrol.
added to a 50-ml erlenmeyerflask containing a Teflon-coatedmagDilithium BenzophenoneDianion (18) from Benzophenoneand
netic stirring bar. The solution was stirred in air until the red
Lithium. Benzophenone(r .82 g, l0 mmol) and rinonadecane
color had faded to pale green-yellow. This solution was treated
(0.824g,3.07 mmol) weredissolvedin 150ml of anhyrJrous
DME.
with 20 ml of water; the organiclayer was separated,the aqueous
Lithium wire (1.0 g, 140 mg-atoms,cut into 0.25-in.pieces;or
layer was extractedonce with l0 ml of ether,and the organicporlithium dispersionwas added and the mixture was allowed to stir
tions were combined, dried (MgSO.r),and analyzed uy gtpc uiing
for I day at room temperatureunder nitrogen to yield a dark red
tetracosaneas an internal standard. Glpc analysis revealed the
solution of 18. Dilithium benzophenone
dianion Lan also be prepresenceof 23 in 50i( yield,with a small amount (ca. l0\) of the
pared in ethyl ether using an analogousprocedure. A pale blue
correspondingbenzhydrolas well as a small amount of i higher
precipitate of lithium benzophenoneketyl forms initiaily; this
boiling material. The authentic sample of the rerl-butylated
precipitateis subsequently
reducedto a red precipitate. vigorous
benzhydrolwas preparedby the reduction of 23 with lithium alustirringis requiredto keepthe precipitatesfiom seitling.
minum hydride.
Lithium Benzophenone
Ketyl (19) from Benzophenone
and Lithium.
using a syringe,another20 ml of the red solutionof 24 was withBenzophenone
(0.4.8
g,2.64 mmol) wasdissolved
in 50 ml of DME.
drawn and was added to a well-stirredsolution of l0 ml of 2 N
Lithium wire (0.0187g,2.64 mg-atoms)wasaddedand the mixture
potassium hydroxide solution. After stirring for 10 min, the
wasallowedto stir at room temperatureundernitrogen for 24hr.
layerswereseparated,the aqueouslayer was extractedwith 20 ml of
Lithium Benzophenone
Ketyl (19) from Benzpinacotand Methylether, the organic portions were combined, dried (MgSOr), and
lithium. Benzpinacol( 1.05g, 2.87mmol) and n-nonadecane
(0.366
analyzedby glpc. Glpc analysisrevealed only 4,4,-di(tert-butyl)g, 1.36 mmol) were dissolvedin 20 ml of DME and were slowly
benzhydrolasa product,in 88f yield.
addedto methvllithiumin ethyl ether(3.90ml,1.62N, 6.31mmol)
Reactionof Phenyllithiumwith carbon Monoxide in the presence
uiacannula. An intenseblue color formed immediately.
of 24. In a typical experiment,a flame-dried, 100-ml. roundThe oxidation of Dilithium BenzophenoneDianion with carbon
botlomedflask equippedwith a Teflon-coatedmagneticstirring bar
Monoxidein Ether. Ten millilitersof an ethersolutionof dilithium
and No-Air stopperwaschargedwith 0.69 g of 4,4,-di(terr-butyl;benzophenonedianion (ca. 0.004 M), which containeda known
(23) (2.5 mmol), 40 ml of freshlydistilledether, and
benzophenone
amount of nonadecane,
was transferredto a flame-driedcentrifuge
0.1 g of lithium wire (14 mg-atoms)in an argon atmosphere. This
tube equippedwith a No-Air stopper r:ia cannula. The solution
mixture was stirred overnight, during which time the solution
was exposedto carbon monoxideand stirred occasionally. After
turned a deep red. Into another flame-dried 100-ml, round20 min the deepred solution of 18 had turned green. An aliquot
bottomed flask equipped with a Teflon-coatedmagnetic stirring
of the solution was quenchedwith degassedmeihanolicpotassium
bar and No-Air stopperwas transferredby cannula20 ml of a 1.25
hydroxideand analyzedusingglpc (TableV).
N solution of phenyllithiumin ether (25 mmol). To this solution
The oxidation of Lithium BenzophenoneKetyl with carbon
was added by cannula the solution of 24 describedabove. This
Monoxide in Ether. Benzpinacol(79.2mg,0.217mmol), nonadecreactionmixture was stirred for 3 hr at 25" (or for 5 hr at -7g.)
ane(58.5mg,0.218mmol), and ca. 25 ml of ether,freshlydistilled
under an atmosphereof carbon monoxide. The reactionmixture
from sodium benzophenone
ketyl, were addedto a flame-dried40was then transferred by cannula to a stirred solution of 20 ml of
ml centrifugetube equippedwith a No-Air stopper and a glassaceticanhydridein 75 ml of freshlydistilledether cooledin an ice
coveredstirringbar. To thissolutionmethyllithium(ca.0.5mmol)
bath. The resultingsuspensionwas washedwith 100 ml of a satwas slowly added by syringewith immediateformation of a light
urated aqueoussolution of sodium bicarbonateand dried (Nazblue precipitate. After 2 hr, this precipitatewas compactedby
so,). This solution was diluted to 300 ml with ether, dotriaconcentrifugationand the blue supernatantsolution was tiansferred
tane was added as an internal standard,and the reaction mixture
by'cannulato another40-ml centrifugetube, which had previously
wasanalyzedby glpc.
been flame-driedand washedwith a solution of methyliithium in
The Reaction of Dilithium Benzophenone
Dianion with p-Ethylether. A 5-ml aliquot of this supernatantsolution wai transferred
phenyllithiumin the Presenceof carbon Monoxide. A mixture of
to a similarlydried centrifugetube and was quenchedwith degassed dilithium benzophenone
dianion (0.093 M, 1.3 mmol, 14.0 ml)
methanolic potassium hydroxide. The remaining solution was
in DME containinga known amountof n-nonadecane
as an internal
allowedto react with carbon monoxidefor 5 hr, duiing which time
standardand p-ethylphenyllithium
(0.08 N, 1.00 mmol, 1.25ml)
the clear blue solution becamecolorless. The colorlesssolution
in ethyl ether was stirredunder I atm pressureof carbonmonoxide
was quenchedwith methanolicpotassiumhydroxide. Analysisof
at room temperaturefor 2 hr. The reactionmixturewashydrolyzed
both quenchedsolutionswascarriedout by glpc (TableV).
with 0.2 ml of aqueousporassiumhydroxidesolution(pH 13).5 ml
oxidations of 18 and 19 with carbon monoxidein DME were
of ether wasadded,and the reactionmixturewas analyzedby glpc.
carriedout usingproceduresanalogousto thoseusedin ether.
a, a- Dip henyl- p-ethylacetophenone
was i dentified by comparison of
spectroscopic
studies. solutions of lithium benzophenone
ketyi
its physicalpropertieswith thoseof an authenticsample.
were obtained by injection of known quantities oi benzpinacol
The Reduction of a,a-Diphenyl-a-hydroxyacetophenone
with
Journal of the American chemical societl, I 95:24 f Not,ember 2g, I9T3
8t33
Dilithium BenzophenoneDianion. Butyllithium in hexane (6.0
(0.957g, 5.1 mmol)
mmol) was addedslowly to 1,2-dibromoethane
in a 40-ml centrifuge tube capped with a No-Air stopper. The
resulting precipitate of anhydrous lithium bromide was washed
four times with 20-ml portions of pentane,dissolvedin 7 ml of hot
DME, and added to 2 mmol of dipotassiumbenzophenonedianion
as internal
in 30 ml of DME containing0.1534g of n-nonadecane
standard in a stoppered40-ml centrifuge tube. The solution was
thoroughly mixed by shaking and the precipitate of potassium
bromide separated by centrifugation. The resulting solution of
was added to a solution of a,a-diphenyldilithium benzophenone?e
(0.0967g, 0.336mmol) in 10 ml of DME.
a-hydroxyacetophenone
The red color of dilithium benzophenonepersistedafter the addition. After stirring at room temperature for 2 hr, the reaction
mixture was hydrolyzed with aqueous potassium hydroxide solution; the aqueouslayer was separatedand extractedwith one 50-ml
portion of ethyl ether, and the organic layers were combined and
dried (NazSOr). Analysis by glpc indicated the presenceof a,adiphenylacetophenone (72%) and c,a-diphenyl-a-hydroxyacetophenone(9%).
Preparation of Other Anions. Lithium phenyl acetylide and
lithium butyl acetylidewere preparedby reaction of the corresponding acetylenewith methyllithium in ether solution. Lithium di(79) Solutions of 18 prepared using this procedure were analyzed
for potassium by hydrolysis and treatment with lithium tetraphenylborate: c-f.D. N. Bhattacharyya, C. L. Lee, J. Smid, and M. Szwarc,
J . P h y s . C h e m . , 6 9 , 6 0 8 ( 1 9 6 5 ) . L e s st h a n l % o f t h e p o t a s s i u mo r i g i nally present as dipotassium benzophenoneremained in solution after
addition of the lithium bromide.
phenylphosphidewaspreparedby the reactionofdiphenylphosphine
with n-butyllithium in THF. Lithium diphenylamidewas prepared by the reaction of diphenylaminewith methyllithium in
THF. Sodium dimsylatewas preparedas describedby Greenwald,
Chaykovsky, and Corey.80 All of the above were reacted with
carbon monoxide at 20Opsi; only sodium dimsylate took up an
appreciable quantity of carbon monoxide (0.5 equiv of carbon
monoxideper equivalentof dimsylateover a 24-hrperiod).
Acknowledgment.
F.
R.
Koeng
carried
out
pre-
Iiminary experimentsin this problem. This work was
assisted substantially by a grant from the Research
Corporation for the purchaseof glpc equipment. Dr.
Charles Hignite, Mr. Brian Andresen, and Professor
Klaus Biemann generously provided us with highresolution spectra and help with glc-mass spectra on
several occasions; this assistancewas provided under
National Institutes of Health Research Grant No.
RR00317 from the Division of ResearchFacilities and
Resources. Professor Barry Sharpless was helpful in
suggestingtechniques for isolation and preparation of
certain of the compounds of interest in this work.
ProfessorRonald Breslow made severaluseful criticisms
of our initial mechanistichypotheses.
(80) R. Greenwald, H. Chaykovsky, and E. J. Corey, J. Org. Chem.,
2 8 , 1 1 2 8( 1 9 6 3 ) .