870
Reactionsof Alkylmercuric Halides with Sodium
Borohydride in the Presenceof Molecular Oxygen'
Craig L. Hill and George M.Whitesides*
Contribution from the Department of Chemistry,
Massachusetts Institute of Technolog)', Cambridge, Massochusetts
ReceiuedAugust 24, 1973
02 I 39.
Abstract: Reaction of alkylmercuric halides with sodium borohydride in dimethylformamide saturated with
molecular oxygen producesalcohols and borate estersin good yields. The products obtained following reaction of
neophylmercuric bromide (l), 1,7,7-trimethylbicyclol2.2.llheptyl-2-mercuricbromide (9), and endo- and exo-norbornyl-2-mercuric bromides (13 and l4) with borohydride in the presenceof oxygen are compatible with a reaction
mechanism involving free, noncaged, alkyl radicals as intermediates. This mechanism finds further support in the
observationsthat rcaction of I with borohydride and oxygen in solutions containing2,2,6,6-tetramethylpiperidoxyl
radical leads to good yields of thc prodr-rctof coupling of neophyl radical with the nitroxyl. Reaction of a-alkoxyl
alkylmercuric halides with borohydridc and oxygen generatcsa-alkoxyl alcohols in good yields; similar reaction of
a-hydroxy alkylmercuric halides does not lead to vicinal diols.
[l kyl r adic alsar e e s ta b l i s h e di n te rm e d i a te si n the re1 1 duc t iv e c lem e rc u ra ti o o
n f a l k y l me rc u ri ch a li desby
me t al hy dr ides . 2- a T h e l o s s o f s te re o c h e mi strythat
occurs during conversionof the carbon-mercury bonds
o f dias t er eom er ic2 -n o rb o rn y l m e rc u ryc o mp o u ndsi nto
carbon-hydrogen bonds, the characteristic structural
re a r r angem ent st h a t a c c o m p a n y d e m c rc u ra ti on of
n o rt r ic y c ly hner c u ryc o mp o u n d s ,a n d th e a b s e n ceof l ,2-phcnyl migration on reduction of neophylmercuric
b ro m ide c om bine to d e fi n e th e l i fe ti me s o f th e i nterrn e diat ealk y l r adi c a l s i n th e s e re a c ti o n sto b e short,
br"rtdo not diffcrcntiate between radical-cage mecha n i s m s ( of whic h o n c p o s s i b l es e q u e n c ei s re p r cscnted
by eq 2 and 3) and rapid radical-chain reactions (eq
4 and5).
]I}I
RHgBr -->
RHgH
(l)
RHgH--> R. + .HgH
R' + 'HgH ---> RH * Hg(O)
(2)
RHgH ---> R.
R' + RH g H-> R H + R . + H g (O)
(-1t
(3)
(s)
S inc e alk y lr nc rc u ri c h a l i d e s a re a m o n g th e most
re a dily av ailablea n d m o s t tra c ta b l e o f o rg a n o metal l i c
co mpounds , ; ' 'and
;
s i n c eth e i r re d u c ti v ed e m e rcurati on
i s a par t ic ular ly f a c i l e p ro c e s s ,th e re a c ti o n o f al kyl me rc ur ic halidesw i th rn e ta l h y d ri d c s s e e msp o t enti al l y
a ttra c t iv eas a m eth o d o f-g e n e ra ti n ga l k y l ra d i c a l sboth
fo r m ec hanis t ics t u d i c s a n d fo r n o s s i L rl eu ti l i z a ti on i n
( l ) S u p p o r t e db y t l r e N a t i o n a l I n s t i t u t e so f H c a l t h , G r a n t s N o . G M 1 6 0 2 0a n c l H L - 1 5 0 2 9 ,a n c l b y ' t h c N a t i o n a l S c i e r r c eF ' o u n c l a t i o nC, r a n t
No. GP-28-5E6X.
( 2 ) G . M . W h i t c s i d e sa n d J . S a n F i l i p p o , J r . ,J . A n t c r . C h e m .9 o c . , 9 2 ,
6 6 1I ( 1 9 7 0 ) .
( 3 ) G . A . G r a y a n c l W . R . J a c k s o n ,. 1 . A n t e r . C l r e m .S o c . , 9 1 , 6 2 0 5
( 1 9 6 9 ) ;D . J . P a s t oa n c l J .G o n t ' t r z ,i b i d . , 9 l , 7 l 9 ( 1 9 6 9 ) .
( 4 ) R e c l u c t i o nl r s i n g o t h c r r c a g c n t sm a y t a k e a n t r n r e l a t e dc o u r s c :
c / . F . R . J e n s e n ,J . J . M i l l e r , S . J . C r i s t o l , a n d R . S . B e c k le y , J . O r g .
C h e r n . 3, 7 , 4 3 4 1( 1 9 1 2 ) .
( 5 ) L . G . M a k a r o v a a r r c l A . N . N c s r n c y a n o v ," M e t h o d s o f E l e r r r c r t t o - O r g a n i cC h c n r i s t r y , " V o l . 4 , N o r t h - H o l l a n c l P u b l i s h i n g C o . ,
Arrsterdam, 1967: t.. G. Makarova, "Organomctallic Reactiorrs,"
V o l . 1 , E . I . B c ' c k c r a n c l M . T s r - r t s u iE, d . , W i l e y - I n t e r s c i e r . l cN
e ,c w
Y o r k , N . Y . , 1 9 7 0 ,p I l 9 f f ' ; V o l . 2 , p 3 3 5f f .
( 6 ) W , K i t c h i n g ,O r g u n o m e t a C
l . h e m . R e a . , 3 , 3 5( 1 9 6 8 ) ; W . K i t c h i n g i n " O r g a n o m e t a l l i cR e a c t i o n s , "V o i . 3 , E . L B c c k e r a n d M . T s u t s u i .
E d . , W i l e y - I n t e r s c i e n cN
c ,e w Y o r k , N . Y . , 1 9 7 2 , p 3 1 9t r .
synthesis, provided that these alkyl radicals survive
sufficientlylong to be accessibleto reagentspresentin
thei r sol uti ons. One previ ous attempt to trap alkyl
radicals produced during reductive demercurationlead
to ambi gl l ous rr-sul ts: reacti on of 2-norbornylm er curi c bronri de w i th sodi um borohydri de i n the pr esence of high concentrations of di-tert-butylnitroxyl
(D TB N O) produced approxi matel y 20% of N, lf - di2 This yield is
tert-bntyl-O-2-norbornylhydroxylarnine.
lower than that expectedfor reaction between free 2norbornyl radi cal sand D TB N O by anal ogy w i t h ot her
but
reacti ons i nvol vi ng thi s or si mi l ar scavenger s, T'8
steric hindrance may contribute to the apparent ineffici ency of the coupl i ng reacti on i n thi s i nstance. This
paper descri besexperi mentsi ntendedto establishconditions under which alkyl radicals, generated from
alkylmercuric halides by reaction with sodium borohydride, can be diverted from the normal path leading
to hydrocarbon by an external reagent. Molecular
oxygen was chosenas radical scavengerin theseexperiments for severalreasons: i t i s hi ghl y reacti vet owar d
rel ati vel yunreacti vetow ard or ganoal kyl radi cal slbut
'
mercury compoundst'and borohydri dei on; i t has sm all
steric requirements: ancl its successfulcoupling with
alkyl moieties derived from organomercury reagents,
particularly those synthesized by oxymercuration,
wor-rldprovide Lrseflllnew methods of forming carbonoxygen bonds and of addi ng functi onal i ty to olef inic
rnoi eti es. These experi mentsw ere al so i nten ded t o
help to diflerentiate between the two types of mechanistic schemes outlined by eq 2-5, by qualitatively
establ i shi ngthe rapi di ty w i th w hi ch the genera t ionand
( 7 ) J . R . T h o r l a s a n d C . A . T o l m a n , J . A m e r . C h e m .S o c . , 8 4 , 2 9 3 0
( 1 9 6 2 ) : S . F . N e l s o r ta n d P . D . B a r t l e t t ,i b i d . , 8 8 , 1 4 3( 1 9 6 6 ) .
( 8 ) B u t y l r a d i c a l s .g e n c r a t c db y r e a c t i o n o f r r - b u t y l ( t r i - n - b u t y l p h o s p h i n c ) s i l v e r ( I )r v i t h 2 , 2 , 6 , 6 - t e t r a m c t h y l p i p e r i d o x( yTlM P O ) , a r e s c a v e n g e c la l r n o s t q u a n t i t a t i v c l yb y t h i s n i t r o r y l r a d i c a l i n e t h e r s o l u t i o n
w h e n [ B u A g P B u , r ]:o 0 . 0 5 M a n d [ T M P O ] o : 0 . 0 5 M : P . E . I { c n d a l l ,
D . E . B c r g b r c i t e r ,a n d G . M . W h i t e s i d c s ,u n p u b l i s h e dw o r k . B u t y l
r a d i c a l s p r o d u c e d b y p h o t o l y s i so f c l i - n - b u t y l b i s ( t r i p h c n y l p h o s p h i n e ) p l a t i n r - r r r r ( I aI )r e s c a v e n g c dw i t h h i g h e l i c i c n c y b y D T B N O : G . M .
W h i t c s i d e s J, . F . G a a s c h ,a n d E . R . S t e d r o n s k y ", / . A m e r . C h e n t .S o c . ,
9 4 . 5 2 5 8( 9 7 2 ) .
(9) Thc rate constantsfor rcaction of alkyl radicals rvith oxygen are
> 1 0 7 l . m o l - r s c c 1 : c / . B . S m a l l e r ,J . R . R e m k o , a n d E . C . A v e r y ,
J . C h e t r t .P h y s . , 4 8 , 5 1 7 4 ( 1 9 6 8 ) ; A . A . M i l l e r a n d F . R . M a y o , . / '
A m e r . C h e t t t . S o c . , 7 81, 0 1 7( 1 9 5 6 ) ;C . M . B a m f o r d a n d M . J . S ' D e war, Proc. Roy. Soc.,Ser. A, 198,252(1949).
[Reprinted from the Journal of the American Chemical Society, 96,870 (1974).]
Copyright I974by the American Chemical Society and reprinted by permission of the copyright owner.
871
CHz
--QHr
,r@g;n*.*
-"3
(QFgnc'zo*
9Hs
@*,h:,
t-u
I
(
o
J
q
I
@[1.1-.
o
--@[5,.
J
lrl
tt3
;
ADDITION TIME ( min )
Figure 1. Product yields from reaction of neophylmercuric bromide
(1) with sodium borohydride in the presenceof oxygen as a function
of the addition rate of l0 ml of a 0.05 M solution of 1 to a O.23M
solution of borohydride in dimethylformamide: (t) yields of
neophyl alcohol (2); (o) yields of benzyldimethylcarbinol (3); and
(A) yields of tert-bulylbenzene. Oxidations were carried out using
0.5 mmol of L and 0.7 mmol of sodium borohydride.
r
Lwq)/
consumption of radical intermediates in reductive
demercurationoccurs.
Results
Products. Initial experiments established that the
reaction of alkylmercuric halides with sodium borohydride in dimethylformamide solution in the presence
of molecular oxygen does yield alcohols as significant
products. Using similar reaction conditions, the
organomercurycompounds were sensiblyinert to oxygen in the absenceof'borohydride ion. The mercury(II) originally presentin the organomercuryreagent is
reducedto mercury(O)in high yield during reduction in
the presenceof oxygen, as it is during reductionsin the
absenceof oxygen.
The reaction conditions used in the major part of the
work reported in this paper are based on the results of
investigationsof the influenceof solvent,order and rate
of addition of reagents,and work-up procedure on the
yield of these alcohols. A number of dipolar aprotic
solvents both dissolved and were chemically inert to
so dium bor ohy dr i d ea n d a l k y l m e rc u ri ch a l i d e s: D MF
rather than dimethyl sulfoxide or hexamethylphosphoramide was selectedfor use on the basisof cost and
co n v enienc cof p u ri fi c a ti o n a n d re m o v a l i n work-up.
Reactions were carried out by adding a solution of
alkylmercuric halide in DMF at room temperatureto a
so l ut ion of s odium b o ro h y d ri d ei n D M F th ro u g h w hi ch
a s t r eam of ox y g e n w a s p a s s e dra p i d l y ; c o m parabl e
results were obtained by adding a solution of sodium
borohydride to an oxygen-saturatedsolution of organomercury compounds. The rate of addition of the solution of alkylmercuric halide to the oxygen-saturated
borohydride solution significantly influenced the partitioning of products between alcohol and hydrocarbon; representativedata used to definereaction conditions are summarizedin Figure I for the conversion
o f n c ophy lm er c u ri cb ro m i d e(1 ) to a m i x tu re o f neophyl
alcohol (2), benzyldimethylcarbinol (3), and tert-butylbenzene (4) (eq 6). Substitution of sodium borodeuteride for sodium borohydride results in similar
yields; no deuterium is incorporated into 2. The
-'l
--] / r
[RHqBrJ
Figure 2. Product yields for reaction of neophylmercuric bromide
(1) and trcrns-2-methoxycyclohexylmercuricbromide (5) with sodium
b o r o h y d r i d e i n t h e p r e s e n c eo f o x y g e n , a s a l u n c t i o n o f b o r o h y d r i d e .
Y i e l d s o f p r o d u c t s a r e r e p r e s e n t e db y : ( n ) n e o p h y l a l c o h o l ( 2 ) ;
(O) benzyldirnethl'lcarbinol (3); (A) tert-butylbenzene(4); (rt
Iruns-2-methoxycyclohexanol (6) ; (o) cis-2-methoxycyclohexanol
( 1 7 ) : ( l ) c y c l o h e x y lm e t h y l e t h e r ( 8 ) .
CH,
I
-C-CHrHg
Ph
I
CHt
I
xatltlr,o:
Br --------->
t)\rF'
CH.'
I
I
CHa
I
ph-c= cH,roH + PhcH,-c-oH
rll
CHI
234
77i ;$s\)
CH'
8% $% )
CHt
I
+ Ph-c-cH3
(6)
CH,
3% (377)
yields shown without parenthesesin eq 6 are those obtained by glpc analysisof the reaction mixture without
work-up imrnediately after addition of the alkylmercuric halide had been completed; the yields in parentheseswere obtained by glpc analysisafter hydrolysis of
the reaction mixture (oide infra). Only the forn-rerare
reproduced in Figure 1. For the concentrationsand
quantities of reagents typically used in these experiments ([R H gB r]s : 0.05 M (0.5 mmol ), [N aBHr io :
0.23 M (0.7 mmol )) the yi el ds of al cohol s di d not increaseif addition of the alkylmercuric halide was carried out over times longer than 6 min. The relative
yields of alcohol and hydrocarbon products also depend on the rate of flow of oxygen through the reaction
sol uti on: underthesecondi ti ons,fl ow ratesgre at ert han
200 ml/min maximized yields of alcohol. The effective
stoichiometry of the reaction with respect to borohydride was establishedby examiningthe yieldsof products obtained by reaction of typical alkylmercuric
hal i des w i th vari ed amounts of borohydri de; Figur e 2
shows data obtained with L and with trans-2-methoxycyclohexylmercuric bromide (trons-S) (eq 7). In this
Hill. Whitesides I Reactionsof'Alkvhnercuric Halides with NaBHr
872
HgBr
N a B H . ,o. ,
{!ou
tl
\-r'"'ocH,
Dl\,{F
6
78
and other instances, 1.2-1.3 mol of borohydride was
required to effect complete demercuration of I mol of
alkylmercurichalide.
In addition to the expectedalcohols and hydrocarbons, product mixtures obtained under these reaction
conditions contained significant quantities of substancesinferred to be alkoxyboron compounds on the
basis of their reactivity. The product balance observed when reaction mixtures were analyzed immediately on conclusion of the addition of solutions of
alkylmercury reagents to the sodium borohydride solution ranged from 50 to 90%; subsequenthydrolysis
reactions increased the product balances to 95*100%.
The hydrolysis reactions were carried out either by treating the initial product mixtures with water or aqueous
acid, extracting the resulting mixtures with diethyl
ether, and analyzingthe etherealphase,or, in many instances,simply by heating the initial product solutions
i n D M F f or s ev era ld a y s a t -l l 0 o ; e a c h o f th e seproceduresled to indistinguishableproduct yields. Representativeyields obtained using each of thesework-up
procedures following the borohydride-induced oxidation and subsequenthydrolysis reactions of 1,7,7-trimethylbicyclol}.2.llheptyl-2-mercuricbromide (9) are
summarized in eq 8; yields for 1 were summarized in
heptane (12) (eq 8); isocamphane and its alcoholic
derivatives were not detected among these products.
Since Wagner-Meerwein rearrangement is believed to
be concerted with formation of a carbonium ion at the
2 position of 9, r0 the absenceof rearranged materials
among the products of its demercurationindicatesthat
a carbonium ion is not an intermediatein this reaction,
but is compatible with a radical intermediate. Similarly, demercuration of 1 in the presence of oxygen
yielded a mixture of 2,3, and 4 (eq 6). Migration of
the phenyl group of neophyl radical is a relatively slow
process(k < 105sec-t at 100" );111,2-arylmi grat ion in
neophyl carbonium is probably concerted with formation of the positivelychargedcenter.r2
Demercuration of endo- and a mixture of endo- and
exo-norbornyl-2-mercuricbromides (13 and 14), in the
presenceof oxygen, yielded the correspondingalcohols
exo- and endo-2-norborneol(15 and 16), in addition to
small amounts of norbornene (17) and norbornane (18)
(eq 9). As previously, the yields without parentheses
NaBH,
oH
02, D\IF'
HgBr
-r
H
l5
3e%(70%)
.-f ----
LY
(e)
OH
16
12%(179'o)
t7
l8
8%(r0%)
Lo/o(r%)
62% 13 +
NaBH,
HgBr
o,. D\'lF
'HgBr
H
10
14
15
16
17
3 7 % ( 7 3 0 / o ) 1 1 0 /(i 1
, 8 ? ; ) 9 7 0( l l % )
++hE
OH
ll
yields(fr) immediately
afterreaction
yields(%) afterhydrolysis
(HrO,rt, 10min)
(aqHrSOr,pH 0, 10min)
yields(fi) afterheating
( 3day s110"
,
)
t2
10
11
t2
41
27
5
60
58
37
36
4
5
61
36
4
eq 6. The yields in the following section include data
obtained both before and after hydrolysis; the differencesin theseyields suggeststhe extent to which alkoxyboron compounds are formed in the demercuration
reaction.
Detection of Intermediate Free Alkyl Radicats. Free
alkyl radicals were established as intermediates using
unexceptional stereochemicaltests. Demercuration of
a mixture of endo and exo diastereomersof 9 in the presence of oxygen led to the correspondingexo and endo
alcohols L0 and 11, and 1,7,7-trrmethylbicyclol2.2.llJournal of the American Chemical Society
18
l90(10/0)
were those obtained at the conclusionof the demercuration reaction; those enclosedin parentheseswere obtained after hydrolysis. The oxidation of 13 and 14
occurs with the loss of stereochemistryat C-2 expected
to result from an intermediate free 2-norbornyl radi cal . The rati os of exo to endo al cohol (76:24 f r om 13
and 77: 23 from the mixture of 13 and 14) are within experimental error of one another, and very similar to
ratios observed for products from other reactions inv olvin g int er mediate 2-norbornyl radicals.2'r 3,| 4
(10) J. A. Berson in "Molecular Rearrangements,"Vol. [, P. deMayo, Ed., Interscience,New York, N. Y., 1963, Chapter 3; H, C.
Brown and H. M. Bell, J. Amer. Chem. Soc.,86, 5006(1964).
( l l ) R . K h . F r e i d l i n a , A d u a n . F r e e - R a d i c a lC h e m . , l , 2 l l 1 1 9 6 5 ) ;
C. Walling in "Molecular Rearrangements,"Part I, P. deMayo, Ed.,
W i l c y , N e w Y o r k , N . Y . , 1 9 6 3 ; C . R i i c h a r t a n d R . H e c h t , C h e m .B e r . ,
98,2460,2471 (1965); G. M. Whitesides,E. J. Panek, and E. R. Stedronsky,J. Amer. Chem. Soc.,94,232 (1972); E. J. Hamilton, Jr., and
H. Fischer, Helu. Chim. Acta,56,795 (1973), and referencescited in
each.
( 1 2 ) A . H , F a i n b e r ga n d S . W i n s t e i n ,J . A m e r . C h e m .S o c . , 7 9 , 1 6 0 8
( 1 9 5 7 ) ; W . H . S a u n d e r sJ, r . , a n d R . H . P a i n e ,i b i d . , 8 3 , 8 8 2( 1 9 6 1 ) .
(13) P. D. Bartlett, G. N. Fickes, F. C. Haupt, and R. Helgeson,
Accounts Chem. Res., 3, 177 (1970); A. G. Davies and B. P. Roberts,
J. Chem. Soc. B, 3ll, 317 (1969); l8l5 (1970); R. Schimpf and P.
Heimback, Chem. Ber., 103, 2122(1970).
96:3 I February6, 1974
873
To establishthat the loss of stereochemistryobserved
in going from organomercury compounds to products
did not reflect epimerization of the mercury reagents
under the reaction conditions, pure 13 and a mixture of
L3 and 14 were allowed to react to approximately 50%
competition, and the remaining organomercury reagents were reisolated. Comparison of the melting
point and infrared spectra of recovered and starting
material demonstratedthat in thesereactions,and presumably in the other reactionsstudied,no loss of stereochemistryin the starting material accompaniesreaction.
A similar conclusion was reachedconcerningthe analogousreactionin the absenceof oxygen.2
Taken together, these product studies are entirely
compatible with the hypothesis that reductive demercuration of alkylmercuric halides in the presence of
molecular oxygen generates intermediate free alkyl
radicals,which are trapped in turn by molecular oxygen
and convertedultimately to alcohols. These data give
no indication that the initial steps in these reactions
leading to the intermediate alkyl radicals differ significantly from the correspondingreactionsin the absence
o f ox y gen,alt hou g h s ma l l y i e l d s o f 3 a re o b s ervedon
reduction of 1 in the presenceof oxygen while isobutylbenzenewas not observedon reduction of 1 in the absenceof oxygen.2 However, they do not define the extent to which the overall reduction-oxidation sequences
i n v olv esc hain or n o n c h a i n p ro c e s s e so, r d e tai l s of the
i n volv em entof t h e b o ro n h y d ri d e i n th e re a c ti on. In
an effort to resolvethese questions,we examined qualitatively the influence of radical inhibitors and of
norbornadiene,a scavengerfor diborane, on the course
of reduction-oxidation of representativealkylmercuric
h alides .
Reactions in the Presenceof Scavengers. The reaction of neophylmercuricbromide (1) with borohydride
and oxygen was carried out in solutions containing
2,6-di-tert-butyl-4-methylphenol,rr' hydroquinone,li'
b e nz oquinone, r r a n d 2 ,2 ,6 ,6 ,te tra m e th y l pi peri doxyl
(T M P O ) . 16 V ery h i g h c o n c e n tra ti o n so f th e se scavengers slowed but did not stop generation of alcohol.
Thus, under conditions in which reaction of 1 with
borohydride and oxygen led to 2 (77 7J, 3 (B%), and 4
(37;), reaction of a mixture composed of 1 and 0.2
equiv of 2,6-di-terl-butyl-4-methylphenolyielded 2
(307,), 3 (3%), and 4 (10%); similar results were obtained with hydroquinone and benzoquinone. These
observations indicate that the conversions of alkylmercuric halides to alcohols are relatively insensitiveto
fiee radical chain inhibitors, and suggestthat any chain
component in these reactionsmust involve short chain
lengths,or that chain initiation is sufficientlyfacile that
( 1 4 ) T h c p r c c l o m i n a n t l yc x o o x i d a t i o n i n t h e s er e a c t i o n si s i n a g r e e n r e r r tw i t h t h e e x p e c t a t i o nt h a t 2 - n o r b o r n y l r a d i c a l s h o u l d r e a c t w i t h
oxygen morc rcadily fiom thc cxo siclc; cf. D. L Davies and S. J. Cristoi,
(1965).
A d c u n .F r e e - R u d i c aCl h e m . , l , 1 - 5 5
(15) K. U. Ingold, Chem. Soc.,Spec.Pabl., No. 24, 285 (1970):
Williarn A. Pryor, "Frcc Radicals,"McGraw-Hill, New York, N. Y.,
1 9 6 6 , C h a p t c r 2 l ; C , W a l l i n g , " F r e e R a c l i c a l si n S o l u t i o n , " W i l e y ,
N c w Y o r k , N , Y . , 1 9 5 7 ,p p 1 6 2 - 1 7 8 , 4 3 0 - 4 3 6 ; K . U . I r r g o l d , C h e m .
R e u . , 6 1 , 5 6 3 ( 1 9 6 1 ) ;L . R e i c h a n d S . S . S t i v a l a ," A u t o x i d a t i o n o f
Hydrocarbons ancl Polyolefins," Marcel Dekker, New York, N. Y.,
| 969, Chapter 3, ar"rdreferencescited in each.
(16) Stcrically hir-rdcrcclnitroxyl groups arc believed to be stable
towarcl hybridic reclucing agents and molecr.rlaroxygen; c/. A. R.
F o r r e s t e r ,J . M . H a y , a n d R . H . T h o m s o r r , " O r g a n i c C h e m i s t r y o f
S t a b l eF r e e R a d i c a l s , "A c a d e m i cP r e s s ,N e w Y o r k , N . Y . , 1 9 6 8 ,C h a p ter 5; E. G. Rozantsev,"Free Nitroxyl Radicals," Plenum Press,Ncrv
Y o r k , N . Y . , 1 9 7 0 ; D . J . I ( o s m a n a n d L . H . P i e t t e ,C h e m .C o m m u t . , 9 2 6
(1969).
i t i s possi bl eto vary the chai n l ength w i dely wit hout
grossl y i nfl uenci ng the character of the rea ct ion. I t
seemsnl ore probabl e that the reacti on ei the r involves
short chai nsor no chai ns.
In a rel ated experi ment,reacti on of a mi xt ur e of L
and 9.6 equi v of TMP O w i th borohydri dean d oxygen
generated 19, the substance expected to result from
coupl i ngof neophylradi cal and TMP O (eq 10 ) ,in good
('H
(.H
I +
TMPO
Frc+_\
I
2 + Ph-('-CH
;.):
-O-N
IY
('H
19(!)57;)
Hc'
)
I.*,
(10)
yield.tT This observation establishedthat essentially
all of the radicals produced by reaction between1 and
borohydri de i on can be scavenged,and i ndi cat est hat
nei therthe conversi onof L to the al cohol s2 and 3 nor
i ts conversi onto 4 can be cagereacti ons.:r)
N orbornene has been used effecti rel y to t r ap t he
di boraneproducedon reacti onof borohydri d eion wit h
a l k y l p a l l a d i u m ( I l )h a l i d e s . r t R e a c t i o n o f 9 a n d o f a
mi xture of 13 and 14 w i th borohydri deand o xygen in
of norbornadi e ne( 20 m ol
the presenceof l arge excesses
per mol of al kyl mercuri chal i de)resul tedi n on ly ca. 6f l
decreasei n the yi el ds of the correspondi ngalcohols.
Thus, the courseof the reacti oni s al so rel ati velyinsensi ti ve to the presenceof materi al sthat mi ght com pet e
w i th the al kyl mercuri c hal i des for any di borane pr esent. For compari son,reacti onof 1 w i th 1.2 equiv of
B H a-TH F i n D MF i n the presencebf oxyg en under
reacti oncondi ti onssi mi l ar to those used for reduct ions
w i th borohydri de yi el ded 2 (20-30' 2,),3 (< 57; ) , and
4 (50*60%). These results are unfortunately not very
i nformati ve mechani sti cal l y. The observati o nt hat t he
presenceof norbornadi enedoes not si gni fi cant lyalt er
the product di stri buti on does not necessarilyindicat e
that di borane or compl exesof B H r w i th D MF ar e not
effecti vehydri de donors tow ard al kyrnercur ichalides
under the reacti oncondi ti ons.but onl y i f theseor ot her
di borane deri vati l ' esare i mportant i n thesere duct ions,
they must have reacti vi tytow ard al kyl mercu r ichalides
that i s at l east comparabl ew i th thei r reacti vit yt owar d
norbornadi ene. C orrespondi ngl y,the fact that neophyl alcohol is prodr-rcedon reaction of BHr with 1
in the presenceof oxygen does not necessarilyimply
that the rate of reducti on of 1 by B H , i s su f hcientt o
(17) In an ef}brt to dctcct interactiorl between I and TMPO beforc
reaction with borohyclriclc, the esr spectrulr of a DMF solution of
M) was comparccl with that of thc samc solution after
TMPO (-10-t
a c l d i t i o r - ro f 1 ; t h c s p e c t r a w e r e n o t d e t c c t a b l y d i f f c r e n t . T h u s , a l though a number of mctal ions havc been shown to complex with diterl-butylnitroxyl rt arrcl TMPO, 1e this and previously reportecl uv
observations2 suggcst that any irrteraction bctrvcetr stable nitroxyl
radicals and alkylmercuric halides is wcak.
( 1 8 ) B . M . H o l l m a n a r - r dT . B . E a m e s , J . A m e r . C h e n t . S o c ' , 9 1 , 5 1 6 8
( 1 9 6 9 ) ; W . B e c k , I { . S c h r n i c l t n e r ,a n d H . J . I { c l l e r , C h e m . B e r . , 1 0 0 , 5 0 3
(1967): W. Beck and I(, Schmidtner, ibid., 100,3363 (1967); B. M.
Hollnratrn ancl T. B. Etrmcs, J. Amer. Chent. Soc., 91, 2169 (1969).
(19) C. M. Palcos, N. M. I(arayarrnis, and M. M. Labes, ChemCommun.,l95 (1970).
(20) The yield of 19 observcd also suggests that the rclatively low
yield (20 i,,") of O-2-norbornyl-i/, N-di- tert- butylhyclroxyl amine formed
on rcduction of 13 or 14 in thc presence of DTBNO: reflccts a stcric
ell'ect on the coupling rcactiort, rather than a protroutlcecl cagc component to thc reaction.
(21) E. Vcdejs and M. F. Salomon, J, Amer. Chem. 9oc.,92,6965
(te70).
HiU. Whitesides I Reactions of-Alkvlntercuric Halides with NaBHt
874
co m pet e wit h r ed u c ti o n o f 1 b y b o ro h y d ri d e i on.
Th u s , t he im por t an c eo f B H a i n th e s ere d u c ti o n si s not
t he obe stablis hedby t he a v a i l a b l ed a ta . N o n e th e l e s s.
se rvat iont hat ) 1. 2 e q u i v o f b o ro h y d ri d e p e r e qui v of
me r c ur ial is r equi re d fo r m a x i m u m y i e l d o f al cohol
(Figure 1) suggeststhat borohydride rather than diborane or its derivativesis the predominant reductant
in thesereactions.
Reactions of Oxymercurated Olefins. The most
readily accessibleclass of organomercury compounds
are those derived from olefins by oxymercuration and
re l a t ed r eac t ions .;'262' C o n v e rs i o n o f a l k oxymercurated olefins to B-alkoxy alcohols by reaction with
borohydride and oxygen takes place in good yield (eq
11), and appearsto offer a convenientmethod for con. H-Rt'
l/">l"h"'
tl
V'r,rn
5.R:CH.
2 0 .R = C H 2 P h
BHq
(),
D\{r'
/'\)'"'
ll+
nH
and consumpti onof free, noncaged,al kyl radi cals. A
plausiblereaction sequencefor the conversionof alkylmercuri c hal i desto al cohol sby borohydri dei on in t he
presenceof oxygen would consist of a modification of
in
the sequencei nvol ved i n the absenceof oxyge n'2'23
theseequati ons" B H " representsa borohydri d e of unspecifiedstructure. The available data give no indication of the probable source of the hydrogen consumed
i n reducti on of R OO. to R OOH ; al kyl mercur ic hydri de, borohydri de,or sol vent (eq 13-15, resp ect ively)
"nII"
RHgBr -->
RHgH --e ft.
R. + O,:-----> ROO.
ROO. * RHgH -->
,oH
ROO. ----> ROOH
SH
"()lt
6, 40ok(52"/,)
(57%)
21. 490/o
ROOH + R. * He(O)
. . 8I I ' '
+
V"tlH
RHgH
ROO. _+
(1)
(4)
(12)
( 13)
(14)
ROOH
(1s)
ROH
(16)
7. 220/n(359/.)
22. 330/o(38%)
ROOH ->
+
seem possible. The observation that ) I equiv of
(r1)all
B H t- i s requi red to achi eve maxi mum conver sion of
Goo
8, 4% (4%)
73. 41"(4Yo)
O
"Bll"
Sok (Sot,,)
2 o / ,( 2 % )
ve rt ing olef insint o p -a l k o x y a l c o h o l s ,p ro v i d e d that a
d i a s t er eom er icm ix tu re o f p ro d u c ts c a n b e to l erated.
Reaction of hydroxymercurated olefins under similar
co ndit ionsleadst o n o u s e fu lp ro d u c t th a t w e h a ve been
a b l e t o det ec t ; f or e x a m p l e , tre a tme n t o f tra n s-Z-hydroxycyclohexylmercuric bromide with borohydride
and oxygen yields cyclohexene (37iJ, cyclohexanol
(4 o , , ( )and
,
c y c lohe x a n o n e(5 % ); th e re ma i n d e r of the
prodr"rctappears as an apparently polymeric material
o f unk nown c om p o s i ti o n . T h e fa c to rs re s p o n si bl efor
the differencein behavior of alkoxymercuratedand hydroxymercuratedolefinsare not readily apparent.
Discussion
S ev er allines of e v i d e n c ee s ta b l i s hth a t th e producti o n ol' alc ohols b y b o ro h y d ri d e d e me rc u ra ti on of
a l ky lm er c ur ic halid e s i n th e p re s e n c eo f o x y g en proce e ds by int er m ed i a tefre e a l k y l ra d i c a l s . F i rst, the
sma ll am ount of r e a rra n g e m e ndt e te c te dd u ri n g oxi dati vc dem er c ur at io no f n e o p h y l me rc u ri cb ro mi d e ,a nd the
absenceof detectablc rearrangementduring oxidative
d e m er c ur at ion of b o rn y l me rc u ri c b ro mi d e , excl ude
ca rbonium ion inte rm e d i a te si n th e s e re a c ti o ns. The
i n volv em ent of in te rme d i a tea l k y l c a rb a n i o n s i s unIi ke ly . bot h by ana l o g yw i th th e re a c ti o ni n th e absence
o f o x y gen, 2and b e c a u s ea c a rb a n i o n w o u l d be expectedto react to a detectableextent with DMF. The
l o ss of s t er eoc he mi s tryd u ri n g c o n v e rs i o no f the carbon-mercury bond to carbon oxygen bonds argues
again a concerted process. All of these observations,
a s w ell as t he s ig n i fi c a n t re a rra n g e m e n to f n eophyl
l o i e ti e s o bserved
mo i et ies t o benz y l d i m e th y l c a rb i n ym
during reaction of 1, the efficient trapping of neophyl
ra d ic als by T M P O , a n d th e s l i g h t b u t d e te c t abl ei nare
h i b it ion of t he r ea c ti o n o f 1 b y ra d i c a l s c a v e n g ers,
co m pat iblewit h a re a c ti o nc o u rs ei n v o l v i n g g e nerati on
( 2 2 ) N . S . Z c f i r o v , R u s s .C h e m .R e c . , 3 4 , 5 2 7 ( 1 9 6 5 ) ;R . C . F a h e y ,
Top. St ereochem.,
3, 2Ji (1968).
al kyl mercuri chal i de to al cohol suggeststhat " BH" in
eq I must be borohydri de i on; the w eak i nfl uence of
that di bor aneis
norbornadi eneon the reacti onsuggests
not essenti alto the reacti on scheme. The obs er vat ion
that deuteri umi s not i ncorporatedi nto 2 deri v edf r om
reacti on of 1 w i th sodi um borodeuteri dei ndi ca t est hat
the conversi on of R OOH to al cohol takes place by
di rect reducti on of the oxygen-oxygen bond, r at her
than by base-catalyzedelimination of water from the
hydroperoxi dew i th formati on of al dehyde or ket one,
followed by reduction of this substance by a borohydride (or deuteride).
In concl usi on,the treatment of al kyl mercu r ic br omi des w i th borohydri dei s a mi l d and convenientway
of produci ng al kyl radi cal s i n sol uti on. If t he r eaction medium is saturated with oxygen, theseradicals
can be converted to al cohol s i n good yi el d. This
i cabl eto other classesof
y
method i s not necessari l appl
reduci ng agents or organomercury compounds; r educti ons of vi nyl i c2a and aromati c2:'mercury com pounds follow mechanisms that differ significantly
from that fol l ow ed by al kyl mercuri chal i desand bor ohydride, and substitution of other reducing agents for
borohydri de i on may al so resul t i n changesi n m echan i s m .a ' 2 ' l
Experimental Section
General Methods. Melting points were obtained using a ThomasHoover melting point apparatus and are uncorrected. Boiling
points are uncorrected. Magnesium sulfate was employed as a
drying agent unless otherwise stated. Nmr spectra were run as
carbon tetrachloride, carbon disulfide, or dimethyl-r/o sulfoxide
solutions on a Varian T-60 spectrometer; chemical shifts are reported in ppm downfield from tetramethylsilane and coupling constants in hertz. Infrared spectra were taken in sodium chloride
c e l l s o r a s p o t a s s i u m b r o m i d e p e l l e t so n P e r k i n - E l m e r M o d e l s 2 3 7 o r
2378 grati-tg spectrometers. Mass spectra were obtained on a
Hitachi Perkin-Elmer Model RMU-6D mass spectrometer. Ana( 2 3 ) S i m i l a r c o t r c l t t s i o t r sh a v c b e e n d r a w r l c o t l c e r r l i t r g t h e f o r m a t i o n
of rearrangccl iilcohols in reactiou of 2,2,2-triphcnylethylmercuric
R. P. Quirk,
chloride with borohyciride ion in the preseuceof oxygell:
J. Org. Chem., 37, 3554 (1972).
(24) J. San Filippo, Jr., and G. M' Whitesidcs, unpublished results.
(25) T. G. Traylor, Chem. Ind. (London), 1223(1959).
Journal o/'the Arnerican ChenticalSocietv I 96:3 I Fehruarl'6, 1974
875
lytical glpc analyses were performed on F&M Model 810 and
Perkin-Model 990 gas chromatographs equipped with flame ionization detectors-and Disc integrators. Response factors were obtained with authentic samples. Products were collected for mass
spectra by glpc using a Hewlett-Packard Model 700 thermal conciuctivity instrument with a 12-ft, 207; UC-W98 column operated
at 140'. All components in the reaction mixtures could be
separated using a S-ft, 15 )( Carbowax 20M on Chromosorb W
column operated at 120" (for hydrocarbon products) and at 190'
for alcohols. Microanalyses were performed by Midwest Microlab, Inc.. Indianapolis, Ind.
All demercurations were carried out in reagent grade N,Ndimethylformamide and employed U.S.P. oxygen. Tetrahyclrofuran was distilled from a dark purple solution of sodium
benzophenone dianion. Pyridine and diethyl ether were distilled from calcium hydride under a nitrogen atmosphere. Merc u r i c b r o m i d e a n d m e r c u r i c a c e t a t ew e r e u s e d w i t h o u t p u r i f i c a t i o n .
Materials. Benzyldinrethylcarbinol (3), tgrt-butylbenzene (4),
isoborneol (10), borneol (11), norbornene (18). norbornane (19),
n o r t r o r n e o l s ( 1 5 a n d l 6 ) , a n c l t h e c y c l o l r e x a n e d i o l sw e r e c o m m e r c i a l s a n r p l e sa n d w e r e u s e d w i t h o u t p u r i f i c a t i o n . H y d r o q u i n o n e ,
L r e n z o q u i n o n e2. .6 - d i - l c r l - b u t y l - 4 - m e t h y l p h e n o l ,a n d n o r b o r n a d i e n e
were conlmerc'ial samples and were purilied before use. 1,7,7Trimelhylbicyclo[2.2.l]heptane (12, bornane), prepared by hyd r o l y s i s o f b o r n y l m a g n e s i u m b r o m i d e . h a d m p I 5 5 - I 5 6 " ( l i t . z 0m p
1 5 6 - 1 5 7 " ) . 2 , 3 . 3 - T r i m e t h y l b i c y c l o [ 2 . 2 . 1 ] h e p t a n e( i s o c a m p h a n e )
was prepared by lryclrogenating camphene over platinum black in
e l l r y l a c e t a t ea t 2 5 " . A s a m p l e o f p u r e e n d o - b i c y c l o [ 2 . 2 . 1 ] h e p t y l - 2 m e r c u r i c b r o m i d e ( 1 3 ) . o b t a i n e d a s a g i f t f r o m D . B e r g b r e i t e r ,h a d
mp 119 120" (lit.zr ffrp 120-121"). Neophylmercuric bromide,2
1 , 7 , 7 - t r i m e t h v l b i c y c l o [ 2 . 2I .] h e p t y l - 2 - r n e r c u r i cb r o m i d e ( 9 ) , ' ?b i c y c l o [ 2 . 2 . 1 ] h e p t y l - 2 - m e r c u r i cb r o m i d e s ( 1 3 a n d 1 4 ) 2 , n e o p h y l a l c o h o l , 2 8
camplrene h ydrate, 2e 2-rnethylcamphenilol,':0 | rutts -2-methoxycyclolrexanol (6),"t cis-2-methoxycyclohexanol (7),"2 tarts-2-benzyl'
o x y c y c l o h e x a n o l ( 2 1 ) , ' r ' ra n d 2 , 2 , 6 , 6 - t e t r a m e t h y l p i p e r i d o x y l( T M PO;rr were prepared using literature procedures. Cyclohexyl
m e t h y l e t h e r ( 8 ) , b p 1 3 5- 1 3 6 " ( l i i . ; ; rf f r p 1 3 5 - 1 3 6 " ) ,a n d c y c l o h e x y l
b e n z y l e t h e r ( 2 3 ) . b p 7 0 ' ( 0 . 0 7 T o r r ) ( l i t . 3 6b p 8 8 ' ( 0 . 1 T o r r ) ) , w e r e
prepared by alkylating sodium cyclohexyl oxide in DMF.
truns-2-Methoxycyclohexylmercuric Bromide (5). Methanol (30
m l ) c o n t a i n i n g 2 4 . 6 S ( 0 . 3 m o l ) o f c y c l o h e x e n ew a s a d d e d s l o w l y t o a
stirred suspension of 79.5 g (0.25 mol) of mercuric acetate in 4iX) ml
of methanol. After 15 min the resulting solution became clear.
I t w a s t r e a t e c lw i t h 3 0 0 m l o f 1 0 f l a q u e o u s p o t a s s i u m b r o m i d e . A
white solid precipitatecl immediately. This solid was recrystallized
twice from methanol to yield 75 e Q6?(,) of trarrs-2-methoxycycloh e x y l m e r c u r i cb r o m i d e : m p 1 1 2 . 5 - 1 1 3 ' ( l i t . r r r r p 1 1 4 1 1 4 . 5 ' ) ;
nmr (DMSO-do) 6 3.4 (3 H, S), 3.2-3.5 (l H, broad), 0.9-2.9 (9 H,
complex).
Anctl. Calcd for CzHuBrHgO:
C , 2 1 . 0 6 ;H , 3 . 5 0 .
tuns-2-Benzyloxycyclohexylmercuric Bromide (20). To a stirred
suspension of 31.9 S (0.1 mol) of mercuric acetate in 150 ml of
benzyl alcohol was added 10.1ml (0.1 mol) of cyclohexene. After
l0 min the resulting clcar solution was treated with 300 ml (0.1
mol) of warm 0.33 N methanolic sodium bromide. A white precipitate formed over a period of 15 min. After 30 min this precipitate was collected by suction filtration and recrystallized from
3:l heptane-benzene to yield 37 g Q97,0 of tans-2-benzyloxyc y c l o h e x y l m e r c u r i cb r o m i d e : m p 8 7 - 8 8 ' ; i r ( K B r p e l l e t ) 3 0 3 0 ( m ) ,
(26) L. Wolfl, JustusLiebigs Ann. Chem.,394,86(1912).
(27) S. Winstein, E. Vogelfanger, K. C. Pandc, and H. F. Ebel,
J. Amer. Chem.^Soc.,
84, 4993(1962).
( 2 8 ) F . C . W h i t m o r c , C . A . W e i s b c r g c r ,a n d A . C . S h i b i c a , J r . ,
J. Amer. Chem..S'oc.,
65" 1469(1943).
( 2 9 ) O . A s c h a n ,C h e m .B e r . , 4 l . l 0 9 2 ( 1 9 0 8 ) .
( 3 0 ) S . M o y c h o a n d F . Z i e n k o w s k i , J u s t u sL i e b i g s A n n . C h e m . , 3 4 0 ,
58 fi905).
( 3 1 ) S . W i n s t e i n a n c l R . B . H c n d e r s o n ,J . A m e r . C h e m . S o c . , 6 5 ,
2196(943).
(32) K. W. Buck, A. ts. Foster, A. Labib, and J. W. Webber, -/.
Chem.Soc., 2846(1964).
( 3 3 ) B . C . M c l { u s i c k , J . A m e r .C h e m . S o c . , 7 0 , 1 9 7 6 ( 1 9 4 8 ) .
(34) T. Toda, E. Mori, and I(. Murayama, Bull. Chem.Soc.Jap.,1904
(t972t.
(35) "Dictionary of Organic Compounds," Vol. II, Oxford Univers i t y P r e s sN
, e w Y o r k , N . Y . , 1 9 6 5 ,p 7 8 5 .
(36) T. A. Cooper and W. A. Waters,J. Chem.Soc. 8,455 (1961).
(37) J. Romeyn aud G, F. Wright, J. Amer. Chem. Soc., 69, 697
(1947).
2 9 0 5( v s ) ,2 8 5 0( s ) ,1 4 3 9( s ) ,1 3 3 5( m ) , 1 1 5 5( m ) , 1 0 2 8( v s ) ,a n d 7 3 7
c m - r ( m ) ; n m r ( D M S O T - d 6 )7 . 4 ( 5 H , s , a r o m a t i c ) , 4 . 5(32 H , s ,
OCHTAT),3.2-3.6(l H, broad singlet,R2C11OR),0.9-2.8(9 H,
complex).
Anal. Calcd for
C. 33 37; H, 3.85.
Bromide (trans-[7).
To a
trans-Z-Hydroxycyclohexylmercuric
s t i r r e d s u s p e n s i o no f 6 3 . 8 g ( 0 . 2 m o l ) o f m e r c u r i c a c e t a t e i n 3 5 0 m l
of water was added 20 ml (0.2 mol) of cyclohexene. The resulting
milky mixture was stirred for 15 min and then treated with 200 ml
(0.2 mol) of 1 rt/ aqueous sodium bromide solution. A white lumpy
solid precipitated immediately. This solid was recrystallized from
ethyl acetate to yield 60 g (Zg %) of trans-2-hydroxycyclohexylmerc u r i c b r o m i d e : m p 1 5 0 . 5 - 1 5 1 . 5 ' ; i r ( K B r p e l l e t ) 3 3 0 0 - 3 6 0 0( s ) ,
2 9 1 9( v s ) , 2 8 5 0( s ) , 1 4 4 2 ( s ) , 1 3 4 9( m ) , 7 2 4 7( m ) , 1 1 5 0 ( s ) , 1 1 0 2( m ) ,
1 0 5 0 ( s ) , 1 0 3 4 ( s ) , a n d 9 5 0 c m - 1 ( s ) ; n m r ( D M S O 3 - d 6 )6 4 . 8 ( 1 H ,
s , O H ) , 3 . 3 -3 . 9 ( 1 H . s , m e t h i n e ) .0 . 9 - 2 . 8( 9 H , c o m p l e x ) .
Anal. Calcd for CoHrrBrHgO: C, 18.97; H,2.92. Found: C,
18.98: H, 2.89.
cis-Z-Benzyloxycyclohexanol (22) was prepared by treatment of
t h e m o n o s o d i u m s a l t o f c r . s - 1 , 2 - c y c l o h e x a n e d i owl i t h b e n z y l b r o r ' i . r - l , 2 - C y c l o h e x a n e d i o (l 9 . 1 g , 7 8 . 5 m m o l ) , p r e mide in DMF.
p a r e d b y t h e m e t h o d o f W i b e r g , 3 8w a s d i s s o l v e d i n 4 0 m l o f D M F .
Sodium amide (3.06 g, 78.5 mmol) was added slowly to this stirred
solution at 0o over a period of 2 min. After addition was com;llete,the resulting mixture was maintained under an argon atmos l r h e r e .s t i r r e d f o r 4 0 n t i n . a n d t h e n t r e a t e d d r o p w i s e w i t h 1 4 . 5 g ( g S
rnmol) of benzyl bromide at 0o. The resulting yellow slurry
turned gray on heating to reflux temperature. After 2 hr of ref l u x i n g , c a . 1 0 0 g o f i c e a n d 1 0 0 m l o f s a t u r a t e da q u e o u sa m m o n i u m
chloride were added to the reaction mixture. The mixture was
extracted with four. lCX)-mlportions of ether. The ethereal phase
w a s d r i e d ( M g S O r ) , c o r t c e n t r a t e d ,a n d d i s t i l l e d u n d e r r e d u c e d p r e s s u r e t o y i e l c l I 1 . 3 g ( - 5 5m m o l . 7 O % ) o f a c l e a r o i l h a v i n g b p 1 0 5 '
(0.01 mm). Elution with ethyl acetate-hexane (1 :5) on a dry
cclumn of silica gel isolated ca. 0.5 g of pure cis-2-benzyloxycyclol r e x a n o l ( 2 2 ) : i r ( C C l , ) 3 5 7 0 ( s ) , 3 3 0 0 - 3 5 0 0( s ) , 3 0 5 9 ( m ) , 3 0 2 3 ( m ) ,
2 9 3 2 ( s ) , 2 8 5 1 ( s ) , 1 7 3 0 ( m ) , 1 4 9 7( m ) , 1 4 5 0 ( s ) , 1 1 7 5 ( s ) , a n d 1 0 8 0
cm-t (s); nmr (CCl.,) 6 7.40 (5 H, s, aromatic), 4.51 (2 H, s,
OCH2AT), 3.3-3.9(2 H, ReCHO),2.9 (1 H, broad, OH), and 0.92.1 (8 H, complex).
Anal. Calcd for CnHraO'z: C, 75.69; H, 8.79. Found: C,
75.72: H, 8.71.
Procedures for f)emercuration in tl{t Presence of Oxygen. Similar procedures were employed in all reactions of organomercury
c o m p o u n d s w i t h s o d i u m b o r o h y d r i d e i n t h e p r e s e n c eo f o x y g e n .
All reactions were carried out at ambient temperature in dimethylformamide solution using 0.50 mmol of alkylmercuric halide, 0.70
mmol of sodium borohydride, and an oxygen flow rate of ca. 3ffi
ml/min unless otherwise specified. A representative procedure
follows.
Demercuration of Neophylmercuric Bromide (1) in the Presence of
Oxygen. Dimethylformamide (3.0 ml) and 0.025 g (O.7mmol) of
sodium borolrydride were placed in a 40-ml centrifuge tube which
was capped with a No-Air stopper containing a l2-in., 15-gauge
stainless steel syringe needle as a vent. Oxygen was supplied to
the centrifr"rgetube from a compressed gas cylinder through a brass
needle valve manifold (Metaframe) and four, 8-in., 2O-gaugestainless steel syringe needles extending to the bottom of the centrifuge
tube. The oxygen flow rate could be regulated precisely by regulating the pressure on the reducing valve at the oxygen tank and
the setting of the needle valves on the manifold. Oxygen was
bubbled through the solution at a flow rate of -300 ml/min. The
dimethylformamide solution of borohydride was flushed with
oxygen for 2 min to saturate the solution and to remove all other
gases from the centrifuge tube. Oxidation was accomplished by
adding 10 ml of a dimethylformamide solution containing 0.5
mmol of 1 and 0.5 mmol of n-pentadecane (an internal glpc standard) dropwise over a 6-min period to the borohydride solution by a
syringe equipped with a 6-in., 2o-gauge syringe needle inserted
through the No-Air stopper. Elemental mercury precipitated
over a period of 7 min. Two minutes after addition of the mercurial solution was complete, all the needles were removed from
the No-Air stopper and the reaction tube was centrifuged to settle
any elemental mercury in suspension. The supernatant was
analyzed without further delay by glpc using an 8-ft, 15fi Carbo-
(38) K. B. Wiberg and
2822 (tes7).
Hill. Whitesides I Reactions of Alkylnlercuric Halides with NaBH t
876
wax 20M on ChromosorbW column operatedat 720" for hydrocarbon product and 190' for alcohol product. Hydrolysisof the
product mixture was accomplishedeither by sealing the 40-ml
centrifugetube with the No-Air stopper and placing the sealed
tube in an oil bath maintainedat ca. 110ofor 3 daysor by adding
6 ml of 1.0 N aqueoussulfuric acid to the reaction mixture, and
extractingthe acidifiedsolution with diethyl ether. The yield of
alcohol as a function of the rate of addition of the alkylmercuric
halide solution to the borohydride solution was determinedby
following thesegeneralproceduresbut varying the time involved
in the addition of the mercurial solution to the solution of the
borohydride. The effectivestoichiometryof alcohol production
with respectto borohy'drideion was determinedby following the
generalprocedurebut varying the startingamountof sodiumborohydride.
Demercurationof NeophylmercuricBromide (1) in the Presenceof
Oxygen and 2,6-Di-tert-butyl-4-methylphenol
and Hydroquinone.
The effectsof thesetwo inhibitorsweredeterminedby following the
generalprocedureexceptthat 0.1 mmol (20 mol I relative to 1)
of inhibitor (0.22e of 2,6-di-terr-butyl-4-methylphenol
or 0.11g of
hydroquinone)was dissolvedin the mercurial solution before the
latter was added to the oxygen-saturated
solution of the reducing
agent. Glpc analysisof the product mixture was carriedout after
20 min. After this length of time the reactionscarried out in the
presenceof inhibitor were not yet complete.
O-Neophyl-2,2,6,6-tetramethylpiperid-l-yl
Oxide (19). To 20
ml of a tetrahydrofuran solution of 0.3 N neophylmagnesium
chloride(6.0 mmol) at -50" was added l0 ml of tetrahydrofuran
containing0.63 g (4 mmol) of 2.2,6,6-tetramethylpiperidoxyl.
The
resultingyellow solutionwas allowedto warm to room temperature
overnight. The resultinglight orangemixture was extractedwith
three 50-ml portions of chloroform. The combinedorganicphase
was washed,dried, and concentrated. Glpc analysis(6-ft, 102,,
UC-W98 on ChromosorbW columntemperatureprogrammedfrom
100to 230'')of the resultingred concentrateshorvedone major peak
and severalsmallerpeaksof long retentiontime, in addition to tertbutylbenzene. The major peak was assignedstructure19 on the
basisof spectraldata: ir (CCl4)f080 (w). 3052(m), 2968(s), 2930
( s ) ,2 8 7 0( s ) ,1 9 4 4( w ) , 1 8 7 1( w ) , 1 8 0 1( w ) , 1 4 6 9( m ) , 1 3 7 2( m ) , 1 3 5 8
( m ) , 1 2 5 5( m ) , 1 2 4 5( m ) , 1 0 4 8( m ) , 9 6 8 ( m ) , a n d 9 1 5 c m - r ( m ) ;
nmr (CCl.)6 7.3(5 H, aromatic),3.70(2 H, CH2O),0.9-1.8 (24 H):
massspectrum(70 eY) ntle 289 (<1, M*), 274 (<1), 177(3). 157
( 2 2 ) , 1 4 3( 8 ) . 1 4 2( 1 0 0 )9, r ( 2 r ) .
Anal. Calcd for Cr'HnHO: mol wt, 289.2397. Found: mol
wt.289.2420.
Demercurationof NeophylmercuricBromide(1) in the Presenceof
Oxygen and 2,2,6,6-Tetramethylpiperidoxyl.
To a solution of 0.5
mmol of 1 and 0.5 mmol of n-pentadecane
internalstandardin l0
ml of DMF was added0.76 g (4.85mmol,9.6-fold molar excess
relativeto 1) of 2,2,6,6-tetramethylpiperidoxyl.
This solutionwas
added to the oxygen-saturated
solution of 0.7 mmol of sodium
borohydridein the usual manner. Elementalmercury was compactedby centrifugationafter 30 min and the red supernatantsolution was analyzeddirectly by glpc (6-ft, 107i on Chromosorb W
columntemperatureprogrammedfrom 100to 230" and an S-ft, 15i,
Carbowax20M on ChromosorbW column operatedat 240").
Demercurationof alkylmercuricbromidesin the presence
of oxygen
and norbornadiene
was carriedout following the generalprocedure
(a 20-foldmolarexcess
with I .01ml ( l0 mmol) of norbornadiene
of
norbornadiene
relativeto alkylmercuric
halide)addedto the DMF
solutionof the mercurialbeforeadditionof the latter to the oxygensaturatedborohydridesolution.
Acknowledgments. We thank David Bergbreiter for
a sample of endo-2-norbornylmercuric bromide (13).
We are also indebted to Larry Trzupek and Phillip
Kendall for assistance in obtaining mass spectra.
High resolution mass spectra were obtained through the
good offices of Dr. C. Hignite, Mr. B. Andresen, and
Professor K. Biemann, under National Institutes of
Health Grant No. RR003l7 from the Division of Research Facilities and Resources.