“ Synthesis of New Wanzlick Carbenes”
MSc. Thesis Defence
Azar Hezarkhani, 2006
Supervisor: Prof. M. Denk
2
tBu
N
C
N
R
?
tBu
N
R
N
N
R
N
tBu
C N
C N C
N
H3C N
C
N
C
H2
N
C
N CH3
N C
N
C
C
N
C N
N
C N C
N C
1
Outline
Background Stable Diamino Carbenes
Poly-thioureas and poly-carbenes
Project I:
The steric limits of diaminocarbene dimerization
-Synthesis of new stable diamino carbenes
-Synthesis of thioureas
-Synthesis of N,N’-dialkyl-ethylenediamines
-Synthesis of 2-chloro-ethylamines
-DFT calculations
Project II:
Attempted synthesis of bis-Wanzlick-carbenes
Synthesis of bis-thioureas
Reduction of bis-thioureas
Future work
2
Motivation
Stable Carbenes: Research Activities 1991+
R
N
C:
1
N
• Nobel prizes: 2005, 1973, 1971
• Application:
R
New Homogeneous Catalysts
…
Arduengo
• Reviews: 10
1991
• Research papers: 800
• Patents: 5
tBu
• Groups active in the field:
Arduengo, Denk, Bertrand, Alder, Herrmann, Nolan, Hahn, Enders, Lappert....
N
C:
2
N
tBu
Wanzlick, Denk
1997
• Key papers:
Betrand, Science
Arduengo, Jacs
Denk, Angew. Chem. Int. Ed. Enl
3
Cl
Cl
PCy3
Ph
Ru
PCy3
H
1995
1st generation Grubbs
Catalyst
N Mes
Mes N
C
Ph
Cl
Cl
Ru
H
PCy3
1999
2nd generation Grubbs
Catalyst
4
CO
OC W CO
OC
CO
Me
C
OMe
1964, Fischer
First metal carbene
complexes
5
Py
E
Py
C

R
linear
Triplet ground state
~ sp
P
Px
Px
R
P
bent
R
C

R
Singlet ground state
~ sp2
6
Electronic Structure of Carbenes (G. Herzberg, 1930+)
Py
E
Py
C
P
Px
Px
R
P
R

R
linear
Triplet ground state
C
bent

R
Singlet ground state
~ sp2
~ sp
Carbene ground state spin multiplicity
depends on:
• Inductive Effects
• Mesomeric Effects
• Steric Effects
7
Synthesis of Stable Carbenes
Reduction
R2N
C
N. Kuhn, M. Denk 1993+
S
R2N
K
R2N
B
- K2S
R2N
C H
R2N
-MeOH
R2N
C
C
- HB
H
R2N
R2N
OMe
 Elimination
Deprotonation
-H2
A.J. Arduengo III 1991+
R2N
H
C
R2N
D. Enders et al. 1995
Future Research
H
1,1-Elimination
8
Stable Carbenes And Their Hetero Analogs
Ad
tBu
tBu
tBu
tBu
N
N
N
N
N
C:
Si:
Ge:
Si:
N
N
N
N
N
Ad
tBu
tBu
tBu
tBu
1991
Arduengo
1991
Denk
1991
Denk
1994
Denk
1994
Denk
Ph
iPr
tBu
tBu
N
N
N
N
Ph
Ge:
N
C:
N
Ph
1995
Enders
iPr
iPr
C
P: Cl
R
Cl
N
C:
P
N
N
N
N
iPr
tBu
tBu
R
1996
Denk
1996
Denk
1996
Denk (tBu)
9
Arduengo (Mes)
1995
Alder
Are Stable Carbenes “Air Sensitive”
tBu
t
N H
N
t
Bu
C
O
tBu
Bu
O2
H2O
N
slow
r.t
N
N
tBu
tBu
t
t
tBu
N
C
C O
Bu
Bu
O2
NH H
H2O
N
C
fast
r.t
N
N
tBu
tBu
N
tBu
O
N
C
C O
M. K. Denk, J. Rodezno, S. Gupta, A. J. Lough, J. Organomet. Chem. 2001
10
Stability of Carbenes: Wanzlick vs Arduengo
R
N
R
N
C
N
R
C
R
N
R
N
N
R
N
R
X
N
R
Do not Dimerize at all
(not even for R = Me)
Arduengo 1991+
11
Stability of Carbenes: Wanzlick vs Arduengo
R
N
R
N
C
C
N
R
N
N
C : :C
N
R
N
N
R
N
R
Do not Dimerize at all
(not even for R = Me)
X
N
R
N
R
N
r.t
Arduengo 1991+
N
N
C
N
C
N
Equilibrium at r.t.
E. Hahn 1999
12
Stability of Carbenes: Wanzlick vs Arduengo
R
N
R
N
C
C
N
R
N
N
N
R
N
R
Arduengo 1991+
N
r.t
C
N
R
N
C
N
R
Do not Dimerize at all
(not even for R = Me)
N
N
16 Kcal
R
N
X
N
R
C : :C
R
N
R
N
R
N
R
N
N
R
N
R
N
R
C
N
Equilibrium at r.t.
N
E. Hahn 1999
C
Dimerize for R < tBu
Reversibel at T > 160 oC
Denk & Hatano 1996
13
The Wanzlick Equilibrium
R
N
C
N
R
R
N
R
N
R
N
N
R
N
R
N
R
C
Dimerize for R = Me, Et, iPr
Reversibel at T > 160 oC
Do not dimerize for R = tBu
Denk & Hatano 1996
Purely Steric ?
Steric and Electronic ?
Steric and electronic influence of R ?
Different substituents R ?
14
Combination of one large and one small Substituents
tBu
N
C
N
R
tBu
N
?
tBu
N
or
C
N
R
tBu R
t
NDimerize
N for R < Bu
tBu
N
N
R
N
R
Reversibel at T > 160 oC
N
N
Denk & Hatano 1996
R
tBu
Do not Dimerize at all
(not even for R = Me)
= Target molecules of this MSc Thesis
Arduengo 1991+
15
Synthesis of Carbene via Thiourea
Alcoholamine => Diamines => Thiourea => Diaminocarbene
R
OH
NH
Cl
SOCl2
. HCl
CH2Cl2 , -SO2
NH
NH
R'
NH
H2O
NH
tBu
tBu
R
NH
5 R-NH2
(CH2O)n
R
N
CH2
N
R'
tBu
S8
-H2S
R
N
C S
N
R'
K
R
a: i-Pr
b: Et
c: Me
d: Ph
R
N
C
N
R'
16
Synthesis of 2-(alkylamino)ethyl chloride hydrochloride
Cl
OH
1.5 SOCl2
NH
² , 8h-4d
CH2Cl2
R
. HCl
+ SO2
NH
R
Reaction time seems to depend on water content
R
Yield
[Lit.]
Yield
This study
m.p. ˚C
[Lit.]
m.p. ˚C
Crude mixture
m.p.˚C sublimed
Me
93 % [a]]
95 %
115-117˚C
113-115 ˚C
209-210 ˚C
Et
91 % [b]]
80 %
223 ˚C
213-215 ˚C
216-217 ˚C
iPr
82 % [c]
82 %
187-188˚C
186-187 ˚C
186-187 ˚C
tBu
80 % [d]]
98 %
203 ˚C
204-205 ˚C
204-205 ˚C
a) Li, R. Farmer, P. S.; Xie, M.; Quilliam, M. A. J. Med. Chem. 1992, 35(17), 3246
b) Lasselle, P.A.; Sundet, S.A.; J. Am. Chem. Soc. 1941, 63, 2374
c) Cope, A. C.; Nace, R. H.; Hatchard, W. R. J. Am. Chem. Soc. 1949, 71, 554
d) Gelbard, G.; Rumpff, P. Bull. Soc. Chim. Fr. 1969, 1161
17
Synthesis of N-tert-butyl-N’alkyl-ethylenediamine
Cl
NH
.HCl
R
5 NH2, H2O
R
NH
N
NH
R Yield Diamine
Me 38%
100oC / 24h
NH
N
NR
Et
89%
NH
iPr
74%
tBu
tBu
tBu
tBu
tBu
tBu
• Large excess of RNH2 required
for formation of diamine,
otherwise piperazine dominate
• Optimized temperature, >
100 : piperazine , < 100 : long
reaction time
• Bomb reaction to retain amine
• Fractional distillation
18
Synthesis of N-tert-butyl-N’-alkyl-imidazolidine-2-thione
tBu
tBu
NH
N
NH
CS2
-H2S
R
C S
N
R
R
65
68
a: Me
b: Et
c: i-Pr
d: t-Bu
Yield: 10-18%
Need better
method
“Synthesis of symmetrical thioureas from formaldehyde aminal and S8
Denk, 2001
19
Synthesis of N-tert-butyl-N’-alkyl-imidazolidine-2-thione
tBu
tBu
NH
NH
(CH2O)n
-H2O
N
CH2
N
R
R
tBu
N
S8
160ÞC, 12h
-H2S
90-91%
C
S
N
R
Recrystallized from hexane
R
Yield
m.p. ÞC
C=S
Me
40 %
96.5 - 97 ÞC
183.1 ppm
Et
15 %
57.5 - 58 ÞC
182.3 ppm
i-Pr
41 %
102.5 - 103.5 ÞC
181.7 ppm
1. Denk, M. K. ; Gupta, S. ; Brownie, J.; Tajammul, S.; Lough, A. J . Chem. Eur. J.
20
2001, 7, 4477.
Synthesis of N-tert-butyl-N’-alkyl-imidazolidine-2-ylidene
tBu
tBu
N
N
C
S
THF , 3 K
C
reflux, 30 mins
N
N
- K2S
R
R
Me
Et
i-Pr
tBu
No dimerization!
R
Just one tBu substituent
is sufficient to prevent
dimerization !
Alkyl
Yield %
13
Me
71 %
239.7 ppm
Et
70 %
238.7 ppm
iPr *
72 %
237.6 ppm
tBu *
90 %
238.2 ppm
C NMR (ppm)
21
Dimerization Energies of Carbenes (DGo)
B98 / 6-31G(d), kcal•mol-1
H
H
H
R
R
R
N
N
N
N
N
N
N
N
N
N
N
N
H
H
H
H
R
R
B98
B98
B98
Increment
(Fully optimized)
Steric
contribution
Me
-26.4
D 3.0
-23.4
-13.2
-14.4
+1.2
Et
-26.4
D 3.3
-23.1
-12.7
-13.2
+0.5
iPr
-26.4
D 4.4
-22.0
-9.9
-8.8
-1.1
tBu
-26.4
D 6.3
-20.1
+25.5
-1.2
+26.7
22
Dimerization Energies of Carbenes
(DGo, B98 / 6-31G(d), kcal•mol-1
Me
B98
DGo
Et
i-Pr
iPr
Me
Me
Et
Et
N
N
N
N
N
N
Me
N
Me
N
Et
N
Et
N
iPr
Ph
t-Bu
tBu
iPr
Ph
Ph
N
N
N
N
N
iPr
N
N
Ph
Ph
N
tBu
tBu
N
N
tBu
-13.2
-12.7
-9.9
-6.5
Electronic -14.4
-13.2
- 8.8
-11.5
-1.1
Steric
~0
~0
~5
~ 26
~0
Dimerize to enetetramine
+25.5
No dimerization
Stable carbene
23
tBu,R Carbenes: DGo, B98 / 6-31G(d), kcal•mol-1)
• Base value (4 x H): DGo dimerization -26.4 kcal
• Electronic contribution from Alkyl groups increments:
t
Bu
Me
t
Bu
Et
Me (3.0), Et (3.3), iPr (4.4), tBu (6.5).
t
i
Bu
Pr
t
Bu
t
Bu
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Bu
Et
Me
t
t
Bu
i
Pr
t
Bu
t
Bu
Fully Optimized:
-0.9
+2.1
+4.0
+25.5
Electronic:
-7.8
-7.2
-5.0
-1.2
Steric:
+6.9
+9.3
+9.0
+26.7
t
Bu
Stable carbene: No dimerization
Conclusion:
tBu, R carbenes would dimerize electronically, but steric hbindrance prevents dimerization
24
13C
Deshielding in Carbenes vs. Aminals
tBu
N
C:
tBu
tBu
N
239.7
238.7
N
C:
C:
tBu
237.6
N
238.7
C:
N
N
N
N
Me
Et
ipr
tBu
168.2
168.7
169.0
175.0
tBu
tBu
tBu
tBu
N
N
N
N
CH2 71.5
CH2 68.9
CH2 69.7
CH2 63.7
N
N
N
N
Me
Et
ipr
tBu
• Deshielding of >C: vs >CH2 (aminal) is a constant increment of ~170 ppm
• Diamino carbene 13C shifts may be predicted from aminal shifts
25
15N
Deshielding in Carbenes vs. Aminals
tBu
tBu
N -224.8
N
C:
N
Me
-258.9
tBu
-321.8
N
Me
-341.4
-225.6
N
-243.7
N
tBu
tBu
N
N
-326.6
Et
N
tBu
tBu
-322.9
N
CH2
C:
-233.4
ipr
-227.6
N
C:
Et
-322.1
tBu
-226.7
N
C:
CH2
N
tBu
-321.4
N
CH2
N
ipr
-316.9
CH2
N
tBu
• Nitrogen in carbene is about 100 ppm more desheilded than aminal.
• The trend of desheilding in N-R is: N-ipr > N-Et > N-Me
• N-R effects on N-tBu NMR shifts. N-tBu would be more desheilded in order of: R= Me > Et > iPr
26
15N
NMR INEPT spectrum of Diamino carbenes
Method : INEPT, J=4 Hz
External reference : Nitro methan
Solvent: C6D6
t-Bu
N
C
N
Et
27
15N
NMR INEPT spectrum of Diamino carbenes
t-Bu
N
C
N
Me
28
Poly-Carbenes
R
N
Known
R
N
C:
C:
N
R
N
R
1
2
80% Unknown
R
N
R
N
R
N
C:
C:
C:
N
N
N
N
N
N
C:
N
R
R
N
N
R
N
R
R
N
R
N
:C
C:
N
R
R
R
N
:C
C:
N
R
N
R
R
N C:
N
C:
N
N C:
R
N
C:
N
C:
N
R
C N
C N C
N
N C
N
C
C
N
C N
C N C
N
N C
R
N
:C
C:
N
N
R
C R
:
N
R
C:
C:
R
N
C:
N
C:
N
R
29
Poly-Carbenes
Monomer:
Me
t-Bu
N
N
N
N
N
C
N
N
t-Bu
N
N
t-Bu
N
N
1
N
Me
13
14
1) Herrmann, W. A.; Elison, M.; Fischer, J.; Köcher, C.; Artus, G.
R. J. Chem. Eur. J. 1996, 2, 772-780. 2) Dias, H. V. R.; Jin, W.
Tetrahedron Lett. 1994, 35, 1365-1366.
N
C
N
R N
N
N
N
N
N R
n = 0, 1, 2, ...
n
15
2
30
Goal of Project II
R
R
N
N
C
N
S
N
n
N
C
S
N
N
K
- K2S
n
N
N
N
C
S
N
N
R
R
31
Chemical Abstract Search: Poly-thioureas?
R
N
S
N
R
N
N
S
R
N
R
N
S
S
S
N
N
N
N
N
N
N
N
S
N
R
Unknown
S
N
R
S
S
N
R
Unknown
Unknown
2 Reference
(R= Me)
1 Reference
(R= H)
N
R
Unknown
32
Synthetic route for synthesis the bis-carbenes
NH2
CS2
C S
N
R
R
Starting
Materials
Aldrich
Cdn $ / mol
R
N
N
C
H
N
NH
R
CH2=O
S
N
K/ THF
²
N
C:
R
C:
Me
Et
iPr
tBu
N
N
C S
N
N
R
R
H
N
NH2
NH2
NH2
NH
Me
NH
Et
NH
iPr
NH
But
NH
Ph
N
Me
492
306
685
3039
516
9300
NH2
NH2
S
33
The Methanol Mystery
or
Synthesis of N-methyl-imidazolodine-2-thione
H3C
CH3
NH
N
MeOH
+
CS2
NH2
C S
old bottle
²
92%
N
H
CH3
NH2
MeOH
fresh bottle
²
NH
C
S
S
H2O
²
zwitterion
Conclusion: Zwitterion decomposition needs some water
34
Synthesis of bis-thioureas
CH3
N
CH3
S
N
2
S
1.2 (CH2O)n
N
Dioxane
² , 8 hr
N
N
H
CH2
S
N
CH3
Solvent
Reaction time
Yield of bis-thioureas
THF
2 weeks
28%
Dioxane
8 hr
75%
Dioxane
8 hr
95%
35
Purification method for bis-thioureas
Method of purification
m.p. ÞC
Recrystallization from Hexane
173-175 ÞC
Recrystallization from THF
179-180 ÞC
Recrystallization from MeOH
181-182 ÞC
Recrystallization from Toluene
183.5-184 ÞC
Sublimation
180-184 ÞC
36
GC-MS of reaction in THF (2 weeks)
CH3
N
S
N
CH2
N
S
N
CH3
37
GC-MS of reaction in Dioxane (8 hr)
CH3
N
S
N
CH2
N
S
N
CH3
38
X-ray structure of bis-thioureas
39
Synthesis of bis-carbene
CH3
CH3
N
N
S
N
CH2
N
C
3 K, THF
X
²
N
CH2
N
S
Reducing agent
C
N
N
CH3
CH3
Reaction
Color of mixture
Result (NMR)
time
3 eq. K
3 mon ths
Brown solution
No reaction
3 eq. K / Na
3 mon ths
Yellow solution
No reaction
3 eq. K / Naphtha lene
2 mon ths
Brown solutiion
New co mpound
3 eq. K / Hexa methyl-disilane
2 mon ths
Brown solution
No reaction
& precipitation
40
Future Works
• Better methods for synthesis of thioureas and carbenes
41
Future work I:
Synthesis of diaminocarbenes from imidazolidinium salts
R
N
CHBr
N
R'
?
?
CBr4
²
R
R
N
CH2
N
R'
S8
-H2S
R
N
K
N
C S
C
N
N
R'
R'
42
Future work II:
Synthesis of diaminocarbenes by dehydrogenation of
imidazolidine
tBu
N
C
N
tBu
N
H2
C
[Pt]
N
r.t
t
H
H
t
Bu
Bu
M. K. Denk, J. Rodezno, S. Gupta, A. J. Lough, J. Organomet. Chem. 2001
R
R
N
CH2
N
R'
[Pd], ² , -H2
?
N
C
N
R'
43
Many Thanks to:
Supervisor: Pro. M. Denk
Committee: Pro. A. Schwan
Pro. W. Tam
Pro. M. Schlaf
Chair :
Pro. P. Rowntree
Labmates:
Feng Lan
Xuan
Kevin
Ahmed
Jeffrey
44
Summary
• Three new stable carbenes synthesized
• Substituent effects(steric and electronic) on dimerization quantified in
kcal (B98/6-31G(d))
• Synthesis of thioureas from imidazolinium salts attempted
• 15N NMR of Carbenes & Aminals to understand bonding
45
Synthesis of disubstituted ethylenediamines I
a) Symmetrical
R
R
O
O
OH
OH
RNH2
O
NH
H2O or EtOH O
NH
LiAlH4 / ether
reflux
NH
NH
R
Et
Bu
Dec
R
R
Rice, L.; Armbrecht, B.; Grogan, C.; Reid, E.; J. Am. Chem. Soc. 75, 1953, 1750.
R
R
Br
RNH2
NH
N
Br
H2O, r.t
NH
N
R
R
R
NH
NR
NH
R
Me
Et
iPr
tBu
Ph
R
Denk, M. K.; Krause, M. J.; Tetrahedron, 2003, 59, 7565.
46
Carbenes: Singlet and Triplet (Inductive Effects)
Li
C
120.46oC Li
E (kcal/mol)
H
C
100.09oC H
S
9.17
T
T
T
C
Li
H
Li
84.27oC
56.07
C
S
132.98oC H
F
p

p

p

C
119.79oC F
S
15.15
F
p

C
103.90oC
F
Electronegativity Increases
p

p
p
3B
1A
1
1B
1A
1
1
1
G3 - Calculation, M. K. Denk, Mar. 16, 2004, Unpublished results
47
Synthesis of first stable carbene
Ad
Ad
O
H
+ 2 NH2 +
N
H
O
Cl
H
N
HCl
O
Ad
HK
N
t-BuOK
N
C
Ad
NH
NH
4C
Ph
Ph
Ph
N
CH(OC2H5)3
-2 C2H5OH
N
Ph
N
150 ÞC
OC2H5
R
H
- C2H5OH
27
9
Ph
Ph
N
R
C
OMe
0.1 mbar,
80oC
N
N
Ph
Ph
28
R
29
R
N
- KCl
N
Cl
a: R= H
C
R
b: R= Ph
N
- tBuOH
Ph
Ph
24
25
• Enders, D.; Breuer, K.; Raabe, G.; Runsink,
J.; Teles, J. H.; Melder, J. P.; Ebel, K.; Brode,
S. Angew. Chem., Int. Ed. Engl. 1995, 34,
1021.c
N
- MeOH
C
N
+ tBuOK
Ph
H
N
Ph
H
N
C
Ph
N
5C
Ph
Ph
26
Ph
Ad
R
K
Me
Me
N
THF, 80oC
C
Me
N
N
C
S
-K2S
Me
N
R
R
30
31
R
a: Me
b: Et
c: i-Pr
48
Synthesis of stable 1H-imidazole-2(3H)-ylidenes (not isolated).
Ph
Ph
N
R
N
a: R= H
C
H
R
N
R
+ tBuOK
- KCl
Cl
R
b: R= Ph
N
- tBuOH
Ph
Ph
12
13
Synthesis of di-phenyl-imidazolidine-2-ylidene by thermal 1,1-elimin
Ph
Ph
NH
CH(OC2H5)3
NH
-2 C2H5OH
N
N
Ph
OC2H5
H
N
150 ÞC
C
- C2H5OH
N
Ph
Ph
Ph
14
15
9
The first commercially available carbene.
Ph
Ph
Ph
N
Ph
H
N
- MeOH
C
C
N
N
OMe
0.1 mbar,
N
80oC
R Ph
Ph
R
N
K
Me
16
N
C
Me
N
R
Me
THF, 80oC
N 17
C
S
-K2S
Me
N
R
R
a: Me
b: Et
c: i-Pr
49
Stable Carbenes: Early Studies
Hans-Werner Wanzlick
Berlin
H.-W. Wanzlick, E. Schikora, Angew. Chem. 1960, 72, 494.
50
Synthesis of Stable Carbenes…
Ph
N
C H X–
N
KOtBu
-KX, HOtBu
Ph
N
C
N
Wanzlick 1970
Ph
Ph
H. W. Wanzlick, H. J. Schönherr, Liebigs Ann. Chem. 1970, 731, 176
H. W. Wanzlick, H. J. Schönherr, Chem. Ber. 1970, 103, 1037.
Ad
N
Cl–
NaH, cat. DMSO
thf, -NaCl, -H2
C H
N
Ad
Ad
N
6 C
N
Ad
Ad
N
C
N
Ad
Arduengo 1991
A. J. Arduengo III et al. J. Am. Chem. Soc. 1991, 113, 361.
iPr
iPr
iPr
Cl–
N
C H
i
Pr N
iPr
LDA, thf
-LiCl, -DA
iPr
N
C
i
Pr N
iPr
R. W. Alder et al, Angew. Chem. Int. Ed. Engl. 1996, 35, 1121.
Alder 1996
51
Alkylation of Ethylene Thiourea
- A Literature Review
H
N
C
S
+ RX
H
N
MeOH
D
H
N
R
C
NaOH
S
N
H
N
H
18
60 - 90%
C
N
H
18
S
+
MeOH
D
19
HN
N
HN
N
C
C
S
S
2HBr
Br
S
R. N. Boyd; M. Meadow,
Analytical Chemistry, 1960, 32, 551-554.
HN
Br
C
N
X
R = Me, Et, iPr, nPr, nBu, sBu,
n-Hexyl, n-Heptyl, allyl, Benzyl
X = Cl-, Br-, I-
H
N
R
NaOH
S
S
C
C
N
72%
HN
N
20
52
J. F. Baer, R. G. Lockwood, J. Org. Chem., 1953, 76, 1162-1164.
C-13 Estimation
Predictions
of different
compounds
ChemNMR
C-13 ChemNMR
Estimation
Chemdraw : 13C-NMR Predictions
2.47
2.47
N
N
S
S
S
N
N
19.7 3.57
68.4
N
N
N
N
5.69
S
S
N
3.57
N
3.57
OH
2.0
N
S
3.57
N
5.53
O
3.57
N
5.53
S
3.57
N
N
S
Experimental :
2.47
N
60
N
S
N
53
Synthesis of Bis-thiourea (Stoichiometry)
2.47
2.47
3.57
N
3.57
N
CH3
S
3.57
N
CH3
S
Dioxane
N
2
S
S
+ 2.4 CH2=O
N
5.69
CH2
ref.,6 hr
N
H
3.57
N
N
5.53
O
3.57
N
5.53
OH
2.0
N
S
3.57
N
S
N
2.47
Yield: 40%
m.p. : 181-183 ˚C
CH3
CH3
N
CH3
S
N
2
Dioxane
S
N
H
N
+ 1.2 CH2=O
CH2
ref.,6 hr
N
S
N
CH3
Yield: 95%
m.p. : 183.5-184 ˚C
54
Formation of imidazolidinium bromide
R
R
N
CH2
CBr4
R
N
H
N
R'
N
R'
R
N
2
H
N
C
N
R'
Br
H
R
N
CH2
H
N
R'
RN
CBr3 Br
C
-HCBr3
+
H2
+
2e-
H +
H2
+
2e-
N
R'
CH2
N-alkyl-1,4-dihydropyridine
RN
55
Strategy for synthesis the diamino carbenes I
R
R
NH
N
CHBr
NH
N
OH
R'
?
?
SOCl2
R'NH2
²
R
R
NH
CBr4
(CH2O)n
R
N
CH2
NH
N
R'
R'
S8
-H2S
R
N
K
N
C S
C
N
N
R'
R'
Pd, -H2
?
56
Synthesis of thiourea from imidazolinium salt (Arduengo salt)
Me
Me
N
CH I
N
1. K2CO3/ MeOH
2. S8, ²
-H2CO3
- K2I
N
S
N
Me
Me
73
74
G.B. Ansell, D. M. Forkey, D. W. Moore, J. Chem. Soc. D., 1970, 1 56b-57l
57
Synthesis of imidazolidinium bromide
Inclusion compound
R
NH
(CH2O)n
NH
R'
Ether
R
N
R
N
CBr4
CH2
N
R'
H . CBr4
N BrR'
reflux, 20h
-CHBr3
R, R'
Me
Et
i-Pr
t-Bu
m.p.=165-168 ÞC
CBr4 crystalls
sublimation
150 ÞC
R
N
Recrystallization
H
N BrR'
Brown residue
194-195 ÞC
from CHCl3
R
N
H
N BrR'
Colorless crystalls
196-197 ÞC
58
Crystal structure of imidazolinium Br salt (inclusion)
59
Synthesis of thioureas by imidazolidinium salt
R
R
MeOH
N
N
CH Br + K2CO3 + S8
S
²
N
N
R
R
R
R
N
MeOH
CH Br + KOH
N
+ S8
R
a: Me
d: tBu
N
S
²
N
R
R
Stronger base?
Different solvent?
60
Dehydrogenation of imidazolidines: potential way
to Wanzlick carbenes
Hydrogenation energies (∆Go , kcal.mol-1)
Reaction
H
N
B98
631Gd
B3LYP
631Gd
-22.62
23.44
-22.30
-18.72
-19.69
-19.38
B1B95
6-31G(d)
CBS-Q
-21.94
-20.36
H
N
C: +H2
CH2
N
H
N
H
Me
Me
N
N
C: + H2
CH2
N
N
Me
Me
tBu
tBu
N
N
C: + H2
CH2
N
N
tBu
tBu
-13.78
-15.59
61
Transfer hydrogenation (computational study)
Hydrogenation energies (∆Go , kcal.mol-1)
Reaction
H2C CH2 + H2
H3C CH3
+ H2
Hydrogen
acceptor
CBS-Q
-28.35
-23.28
-29.19
-26.78
-20.73
-18.64
-21.67
-18.98
B98
631Gd
∆G0= -6.95
tBu
tBu
N
N
C:
B3LYP
631Gd
B1B95
6-31G(d)
+ H2
CH2
N
N
tBu
tBu
-13.78
Hydrogen donor
-15.59
62
Transfer hydrogenation (Experiments)
tBu
tBu
N
N
CH2
+
Pt, C6D6
N
tBu
iPr
190 ÞC
67d
65d
+
CH2
N
N
tBu
iPr
67d
Pd , toluene
tBu
N
65c
tBu
N
N
N
C:
tBu
CH2
tBu
C:
N
65c
tBu
N
+
C:
190 ÞC
+
N
tBu
67d
63
From Poly-Thioureas To Poly-Carbenes
N
N
R
N
C
C
S
S
N
R
N
R
K/ THF
R
N
N
N
:
:
Dimerization
R
R
N
N
• New Homogenous Catalyst
C
C
• Carbene complexes
?
N
N
N
N
N
N
R
R
• Electrochemical storage
(Battery without metal)
• Strong organic reducing agent
• Carbene Complex
64
Enetetramines: Reducing agents
Reducing agent
CH3
N
2
CH2
C
N
CH3
Dimerize for R < tBu
10.5 eV
CH2
Reversibel at T > 160 oC
CH3
CH3 & Hatano 1996
Denk
N
N
C
C
6.06 eV
N
N
CH3
R
N
R
N
C
N
R
C
N
R
1 IP (eV)
Do
Dimerize at all
CHnot
3
(not even for R = Me)
CH3
CH3
N
N
N
N
N
N
N
N
CH3
CH3
R
N
R
N Me3Ge N
N
R
N
R
Arduengo 1991+
5.95 eV
N GeMe3
5.87 eV
Equilibrium at r.t.
E. Hahn 1999
65
66
bis(3-methylimidazolidine-2-thione-1-yl)methane
N
S
N
N
S
N
N
S
1,3-dimethylimidazolidine-2-thione
N
bis(3-methyl-2-methyleneimidazolidin-1-yl)methane
N
N
N
N
N
CH2
N
1,3-dimethylimidazolidiniumbromide
bis(3-methylimidazolidin-1-yl)methane
67
adamantyl
quinone
guanidine
O
O
NH2
C•
HN
NH2
68
Magnetic Properties of 15N, 14N, 13C and 1H isotopes
Magnetic properties of the
Nucleus
14
N, 15N, 13C, 1H isotopes.
Natural
I
Relative
abundance %
Spin
sensitivity
99.98
1/2
1
13
1.11
1/2
1.76  10 -4
14
99.63
1
1.00  10 -3
15
0.37
1/2
3.52  10 -6
1
H
C
N
N
• 15N is 283800 times less sensitive than 1H NMR !!!
•
14N
has higher sensitivity than 15N but it is quadropolar and
has broad peaks.
69
Singlet-Triplet Gaps for Carbenes (kcal/ mol)
Singlet
Triplet
H
C:
H
Exp.
9.05a
F
C:
H
Cl
C:
Cl
F
C:
F
H2N
C:
H2N
H
N
H
N
C:
N
H
C:
OC:
N
H
-56.6a
-14.7a
CBS-Q c
8.1
-15.6
-21.0
-56.9
-55.9
-72.9
-86.5
-139.6
G3 c
9.5
-14.5
-21.0
-56.1
-55.3
-72.4
-85.3
-138.0
CBS-APNO c
9.0
-14.5
W1 c
9.2
• Very few experimental S/T energies (H2C, F2C and FHC)
• Li2C is linear but all other T-carbenes are bent !
• All heavier carbenes (H2Si: etc.) have singlet ground state
• Atomic carbon most reactive triplet carbene
• Vinylidenes R2C=C:most reactive singlet carbenes
• T-carbenes react as radicals, S-carbenes as strong electrophiles
a) C.-H. Hu, Chem. Phys. Lett. 1999, 309, 81-80.
b) M. D. Su, C.-H. Hu, Chem. Phys. Lett. 1999, 308, 283-288.
c) M. K. Denk, unpublished.
70
13C-
NMR (ppm)/ Electronic Stabilization
Experimental data
* Computational data( CBS-APNO)
Rings / Chains
Aryl/ Alkyl
Mes
iPr
iPr
N
N
C
C
N
Mes
244.5
N
N
iPr
C
iPr
N
H
F
C
C
H
F
iPr
iPr
236.8
255.5
300.87 *
1483.88 *
Aromaticity
F
F
iPr
Ph
N
C
N
iPr
205.9
C
C
F
F
N
C
F
S
F
254.3
C
F
F n
Teflon
Nitrogen / Sulfur
• Carbenes have highly deshielded carbon NMR shift
• Unstabilized H2C: may serve as a refrence point for the high electronic stabilization71of
other carbenes