1

NC

N

CN

N CN C

CNCN

NC

N

C

NC

C

“ Synthesis of New Wanzlick Carbenes”

MSc. Thesis Defence

Azar Hezarkhani, 2006

Supervisor: Prof. M. Denk

NC

NNC

NCH2

CH3H3C

NC

N

tBu

R

N

N

N

N

tBu

R

R

tBu

?2

2

Outline

-Synthesis of new stable diamino carbenes-Synthesis of thioureas-Synthesis of N,N’-dialkyl-ethylenediamines-Synthesis of 2-chloro-ethylamines-DFT calculations

Project I: The steric limits of diaminocarbene dimerization

Project II: Attempted synthesis of bis-Wanzlick-carbenes

Synthesis of bis-thioureasReduction of bis-thioureas

Background Stable Diamino CarbenesPoly-thioureas and poly-carbenes

Future work

3

Motivation

Stable Carbenes: Research Activities 1991+

1

2

N

C:

N

R

R

1991

Wanzlick, Denk

1997

N

C:

N

tBu

tBu

Arduengo• Reviews: 10

• Research papers: 800

• Patents: 5

• Groups active in the field: Arduengo, Denk, Bertrand, Alder, Herrmann, Nolan, Hahn, Enders, Lappert....

• Key papers: Betrand, Science Arduengo, Jacs Denk, Angew. Chem. Int. Ed. Enl

• Nobel prizes: 2005, 1973, 1971

• Application:

New Homogeneous Catalysts …

4

Mes MesNC

N

RuCl Ph

ClPCy3

H

PCy3

RuCl Ph

ClPCy3

H

19951st generation GrubbsCatalyst

19992nd generation GrubbsCatalyst

5

W

CMe OMe

COOCCOOC

CO

1964, FischerFirst metal carbenecomplexes

6

R C R C

R

R

~ sp ~ sp2

Triplet ground state Singlet ground state

Py

Px

Pπ

σ

linear bent

E

Py

Px

Pπ

σ

7

Electronic Structure of Carbenes (G. Herzberg, 1930+)

R C R C

R

R

~ sp ~ sp2

Triplet ground state Singlet ground state

Py

Px

Pπ

σ

linear bent

E

Py

Px

Pπ

σ

Carbene ground state spin multiplicity depends on:

• Inductive Effects• Mesomeric Effects

• Steric Effects

8

A.J. Arduengo III 1991+ D. Enders et al. 1995

N. Kuhn, M. Denk 1993+

Synthesis of Stable Carbenes

1,1-Elimination

R2NC

R2N

H

H

-H2

Future Research

R2NC

R2N

R2N

CR2N

H

R2NC

R2N

S

R2NC

R2N

Deprotonationα Elimination

OMe

H-MeOH B

- HB

K

Reduction

9

Stable Carbenes And Their Hetero Analogs

NC:

N

Ad

Ad

NSi:

N

tBu

tBu

NGe:

N

tBu

tBu

1994Denk

1991Denk

NSi:

N

tBu

tBu

NGe:

N

tBu

tBu

1991Arduengo

1991Denk

1994Denk

N

P:N

tBu

tBu

N

PN

tBu

tBu

ClCl

NC:

N

N

Ph

Ph

Ph

N

C:N

R

R

NC

iPriPr N

iPr

iPr

1995Enders

1995Alder

1996Denk

1996Denk (tBu)

Arduengo (Mes)

1996Denk

10

Are Stable Carbenes “Air Sensitive”

M. K. Denk, J. Rodezno, S. Gupta, A. J. Lough, J. Organomet. Chem. 2001

NC

N

tBu

tBu

NC

N

tBu

tBu

O2NC

N

tBu

tBu

NC

N

tBu

tBu

O

O

O2

H2O

H2ONH

CN

tBu

tBu

H

O

N

CN

tBu

tBu

H

O slow

fast

r.t

r.t

11

Stability of Carbenes: Wanzlick vs Arduengo

Do not Dimerize at all(not even for R = Me)

Arduengo 1991+N

CN

R

R

XN

N

N

N

R

R

R

R

NC

N

R

R

12

Stability of Carbenes: Wanzlick vs Arduengo

Do not Dimerize at all(not even for R = Me)

Arduengo 1991+

Equilibrium at r.t. E. Hahn 1999

NC

N

R

R

XN

N

N

N

R

R

R

R

NC

N

R

R

NC

N NC

N NC

NNC

N::

r.t

13

Dimerize for R < tBuReversibel at T > 160 oC

Denk & Hatano 1996

Stability of Carbenes: Wanzlick vs Arduengo

Do not Dimerize at all(not even for R = Me)

Arduengo 1991+

Equilibrium at r.t. E. Hahn 1999

NC

N

R

R

N

N

N

N

R

R

R

R

NC

N

R

R

NC

N

R

R

XN

N

N

N

R

R

R

R

NC

N

R

R

NC

N NC

N NC

NNC

N::

r.t

16 Kcal

14

Purely Steric ?

Steric and Electronic ?

Steric and electronic influence of R ?

Different substituents R ?

NC

N

R

R

N

N

N

N

R

R

R

R

NC

N

R

R

The Wanzlick Equilibrium

Dimerize for R = Me, Et, iPr Reversibel at T > 160 oC

Do not dimerize for R = tBuDenk & Hatano 1996

15

Dimerize for R < tBuReversibel at T > 160 oC

Denk & Hatano 1996

Combination of one large and one small Substituents

Do not Dimerize at all(not even for R = Me)

Arduengo 1991+

NC

N

tBu

R

N

N

N

N

tBu

R

tBu

R

NC

N

tBu

R

N

N

N

N

tBu

R

R

tBu

or?

= Target molecules of this MSc Thesis

16

Synthesis of Carbene via ThioureaAlcoholamine => Diamines => Thiourea => Diaminocarbene

Ra: i-Prb: Etc: Med: Ph

NH

OH

tBu

NH

Cl

tBu

HCl

NH

NH

tBu

R

.SOCl2

CH2Cl2 , -SO2

5 R-NH2

H2O

NH

NH

R

R'N

CH2

N

R

R'

N

C

N

R

R'

S

N

C

N

R

R'

(CH2O)n KS8

-H2S

17

Synthesis of 2-(alkylamino)ethyl chloride hydrochloride

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), 3246b) Lasselle, P.A.; Sundet, S.A.; J. Am. Chem. Soc. 1941, 63, 2374c) Cope, A. C.; Nace, R. H.; Hatchard, W. R. J. Am. Chem. Soc. 1949, 71, 554d) Gelbard, G.; Rumpff, P. Bull. Soc. Chim. Fr. 1969, 1161

Reaction time seems to depend on water content

NH

Cl

R

NH

OH

R

HCl

CH2Cl2

.1.5 SOCl2

∆, 8h-4d

+ SO2

18

Synthesis of N-tert-butyl-N’alkyl-ethylenediamine

• 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

NH

NR

tBu

N

N

tBu

tBu

NH

tBu

NH2

R

NH

NH

R

tBu

HClNH

Cl

tBu

5.

100oC / 24h

H2O

R Yield Diamine

Me

Et

iPr

, 38%

89%

74%

19

Synthesis of N-tert-butyl-N’-alkyl-imidazolidine-2-thione

-H2SNH

NH

tBu

R

CS2

65 68

a: Meb: Etc: i-Prd: t-Bu

R

NC

N

S

tBu

R

Yield: 10-18%

Need better method

“Synthesis of symmetrical thioureas from formaldehyde aminal and S8

Denk, 2001

20

Synthesis of N-tert-butyl-N’-alkyl-imidazolidine-2-thione

R Yield m.p. ˚ C C=S

Me 40 % 96.5 - 97 ˚C 183.1 ppm

Et 15 % 57.5 - 58 ˚C 182.3 ppm

i-Pr 41 % 102.5 - 103.5 ˚C 181.7 ppm

1. Denk, M. K.; Gupta, S.; Brownie, J.; Ta jammul, S.; Lough, A. J. Chem. Eur. J.

2001, 7, 4477.

NH

NH

tBu

S8

160˚C, 12h

(CH2O)n

N

N

CH2

tBu

RR

NC

N

S

tBu

R

90-91%

-H2S-H2O

Recrystallized from hexane

21

Synthesis of N-tert-butyl-N’-alkyl-imidazolidine-2-ylidene

Alkyl Yield % 13C NMR (ppm)

Me 71 % 239.7 ppm

Et 70 % 238.7 ppm

iPr * 72 % 237.6 ppm

tBu * 90 % 238.2 ppm

Just one tBu substituent is sufficient to prevent dimerization !

No dimerization! THF

reflux, 30 mins

, 3 K

N

C

N

S

tBu

R

N

N

C

tBu

R - K2S

R

Me Eti-PrtBu

22

B98 B98 B98 Increment Steric (Fully optimized) contribution

Me -26.4 3.0 -23.4 -13.2 -14.4 +1.2

Et -26.4 3.3 -23.1 -12.7 -13.2 +0.5

iPr -26.4 4.4 -22.0 -9.9 -8.8 -1.1

tBu -26.4 6.3 -20.1 +25.5 -1.2 +26.7

Dimerization Energies of Carbenes (Go)B98 / 6-31G(d), kcal•mol-1

N

N

H

H

N

N

H

R

N

N

H

H

N

N

H

H

N

N

R

R

N

N

R

R

23

Go -13.2 -12.7 -9.9 -6.5 +25.5

Me Et i-Pr Ph t-Bu

Dimerization Energies of Carbenes (Go, B98 / 6-31G(d), kcal•mol-1

Electronic -14.4 -13.2 - 8.8 -11.5 -1.1

N

N

Me

Me

N

N

Me

Me

N

N

Et

Et

N

N

Et

Et

N

N

iPr

iPr

N

N iPr

iPr

N

N

Ph

Ph

N

N

Ph

Ph

N

N

tBu

tBu

N

N tBu

tBu

Steric ~ 0 ~ 0 ~ 0 ~ 5 ~ 26

Dimerize to enetetramine No dimerizationStable carbene

24

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

• Base value (4 x H): Go dimerization -26.4 kcal

• Electronic contribution from Alkyl groups increments: Me (3.0), Et (3.3), iPr (4.4), tBu (6.5).

tBu,R Carbenes: Go, B98 / 6-31G(d), kcal•mol-1)

N

N

tBu

Me

N

N tBu

Me

N

N

tBu

Et

N

N tBu

Et

N

N

tBu

iPr

N

N tBu

iPr

N

N

tBu

tBu

N

NtBu

tBu

Conclusion: tBu, R carbenes would dimerize electronically, but steric hbindrance prevents dimerization

Stable carbene: No dimerization

25

13C Deshielding in Carbenes vs. Aminals

N

N

Me

tBu

C:

N

CH2

N

Me

tBu

N

CH2

N

Et

tBu

N

CH2

N

ipr

tBu

N

N

Et

tBu

C:

N

N

ipr

tBu

C:237.6 238.7 239.7

• Deshielding of >C: vs >CH2 (aminal) is a constant increment of ~170 ppm

• Diamino carbene 13C shifts may be predicted from aminal shifts

71.5 69.7 68.9

168.2 169.0 168.7

N

N

tBu

tBu

C:

N

N

tBu

tBu

CH2

238.7

63.7

175.0

26

15N Deshielding in Carbenes vs. Aminals

-224.8

-258.9

-341.4

-225.6

-243.7

-322.1

-326.6 -316.9

-322.9

-226.7

-233.4

-321.8

N

N

Me

tBu

C:

N

CH2

N

Me

tBu

N

CH2

N

Et

tBu

N

CH2

N

ipr

tBu

N

N

Et

tBu

C:

N

N

ipr

tBu

C:

• 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

N

N

tBu

tBu

CH2

N

N

tBu

tBu

C:

-227.6

-321.4

27

15N NMR INEPT spectrum of Diamino carbenes

N

N

t-Bu

Et

C

Method : INEPT, J=4 Hz External reference : Nitro methan

Solvent: C6D6

28

N

N

t-Bu

Me

C

15N NMR INEPT spectrum of Diamino carbenes

29

Poly-Carbenes

1 2

NC:

N

NC:

NN:C

N

:CN N

C:N

NC:

N

NC:

N

NC:

N

C:N

NC:

NKnown

NC:

N

NC:

N

NC:

N

NC:

N

NC:

N

C:N

N C:

NC:

N

C:N

NC:

NN:C

N

NC

N

CN

N CN C

CNCN

NC

N

C

NC

C

C

R

R

R

R

R

R

R

R

R

RR

R

RRRR

R R RR

R

R

R

R

R

R R

80% Unknown

30

Monomer:

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

1

N

N

N

N

Me

Me

N

N

N

N

N

Nt-Bu

t-Bu

t-Bu

13 14

N N N N N NR R

n

15

n = 0, 1, 2, ...

Poly-Carbenes

N

C

N

2

31

Goal of Project II

N

C

N

N

C

N

N

C

N

R

R

S

S

S

K- K2S

N

N

N

N

N

N

R

R

nn

32

Unknown

2 Reference (R= Me)

Unknown

1 Reference (R= H)

Chemical Abstract Search: Poly-thioureas?

Unknown Unknown

N

N

N

N

N

N

R

R

S

S

S

N

NS

N

NS

N

NS

N

NS

N

NS

N

NS

R

RR

R

R

R

33

Synthetic route for synthesis the bis-carbenes

R

Me Et iPr tBu

NH

NH2

R

N

HN

R

C SCS2

N

N

R

C S

N

NC S

R

CH2=O K/ THF

N

N

R

C

N

NC

R

∆

NH

NH2

ButNH

NH2

Me

NH

NH2

iPrNH

NH2

Et

NH

NH2

Ph

StartingMaterials

AldrichCdn $ / mol

492 306 685 3039 516

N

HN

Me

S

9300

34

The Methanol Mysteryor

Synthesis of N-methyl-imidazolodine-2-thione

NH2

NH

CH3

NH

N

C S

H3C

CS2+

H2O

∆

NH

NH2

CH3

C

S

S

zwitterion

92%

MeOHfresh bottle

old bottle

MeOH

∆ ∆

Conclusion: Zwitterion decomposition needs some water

35

Synthesis of bis-thioureas

NH

N

S

CH3

N

N

S

N

NS

CH2

CH3

CH3

2

∆, 8 hrDioxane

1.2 (CH2O)n

Solvent Reaction time Yield of bis-thioureas

THF 2 weeks 28%

Dioxane 8 hr 75%

Dioxane 8 hr 95%

36

Purification method for bis-thioureas

Method of purification m.p. ˚C

Recrystallization from Hexane 173-175 ˚C

Recrystallization from THF 179-180 ˚C

Recrystallization from MeOH 181-182 ˚C

Recrystallization from Toluene 183.5-184 ˚C

Sublimation 180-184 ˚C

37

GC-MS of reaction in THF (2 weeks)

N

N

S

N

N

S

CH2

CH3

CH3

38

GC-MS of reaction in Dioxane (8 hr)

N

N

S

N

N

S

CH2

CH3

CH3

39

X-ray structure of bis-thioureas

40

Synthesis of bis-carbene

Reducing agent Reaction

time

Color of mixture Result (NMR)

3 eq. K 3 months Brown solution No reaction

3 eq. K / Na 3 months Yellow solution No reaction

3 eq. K / Naphthalene 2 months Brown solutiion New compound

3 eq. K / Hexamethyl-disilane 2 months Brown solution

& precipitation

No reaction

N

NS

N

NS

CH2

CH3

CH3

3 K, THF

∆

NC

N

NC

NCH2

CH3

CH3

X

41

• Better methods for synthesis of thioureas and carbenes

Future Works

42

Future work I:Synthesis of diaminocarbenes from imidazolidinium salts

N

CH2

N

R

R'

N

CHBr

N

R

R'

N

C

N

R

R'

S

N

C

N

R

R'

CBr4

KS8

? ?

-H2S

43

Future work II:Synthesis of diaminocarbenes by dehydrogenation of

imidazolidine

N

CH2

N

R

R'

N

C

N

R

R'

?

[Pd], ∆, -H2

N

C

N

tBu

tBu

N

C

N

tBu

tBu

H

HH2

[Pt]

r.t

M. K. Denk, J. Rodezno, S. Gupta, A. J. Lough, J. Organomet. Chem. 2001

44

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

Many Thanks to:

45

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

46

Synthesis of disubstituted ethylenediamines Ia) Symmetrical

Rice, L.; Armbrecht, B.; Grogan, C.; Reid, E.; J. Am. Chem. Soc. 75, 1953, 1750.

Denk, M. K.; Krause, M. J.; Tetrahedron, 2003, 59, 7565.

NH

NH

R

R

NH

NR

NH

R

R

N

N

R

R

RNH2Br

Br H2O, r.t

R

MeEtiPrtBuPh

LiAlH4 / ether

OH

OH

NH

NH

R

R

reflux

O

O NH

NHO

O

R

R

H2O or EtOH

R

Et Bu Dec

RNH2

47

Carbenes: Singlet and Triplet (Inductive Effects)

Electronegativity Increases

S

T

S

TT

15.159.17

56.07

E (kcal/mol)

S

G3 - Calculation, M. K. Denk, Mar. 16, 2004, Unpublished results

C

LiLi84.27oC

C

Li

Li

120.46oC

C

H

H

132.98oC

C

H

H

100.09oC

C

F

F

103.90oC

C

F

F

119.79oC

σ

pπ

σ

pπ

σ

pπ

σ

pπ

σ1pπ1 σ2 σ1pπ

1 pπ2

3B11A1

1B11A1

48

Synthesis of first stable carbene

Cl

N

N

Ad

Ad

HN

CN

Ad

Ad

O

O

+ NH2

Ad

2 + OH

H

HCl

t-BuOK

HK

4C 5C

K

RN

NC S

RMe

Me N

NC

R

RMe

Me Ra: Meb: Etc: i-Pr

THF, 80oC

30 31

-K2S

N N

NC

H

Ph

PhPh

OMe N N

NC

Ph

PhPh

28 29

0.1 mbar, 80oC- MeOH

NH

NHPh

Ph26

CH(OC2H5)3-2 C2H5OH N

NPh

PhHOC2H5

- C2H5OH NC

NPh

Ph27 9

150 ̊ C a: R= Hb: R= Ph

Cl- KCl

- tBuOHN

NPh

Ph

HN

CNPh

Ph

+ tBuOK

24 25

R

R

R

R

• 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

49

a: R= Hb: R= PhCl

- KCl- tBuOHN

NPh

Ph

HN

CNPh

Ph

+ tBuOK

12 13

RR

RR

Synthesis of stable 1H-imidazole-2(3H)-ylidenes (not isolated).

NH

NHPh

Ph14

CH(OC2H5)3-2 C2H5OH N

NPh

PhHOC2H5

- C2H5OH NC

NPh

Ph15 9

150 ̊ C

Synthesis of di-phenyl-imidazolidine-2-ylidene by thermal 1,1-elimination.

N N

NC

H

Ph

PhPh

OMe N N

NC

Ph

PhPh

16 17

0.1 mbar, 80oC- MeOH

The first commercially available carbene.

K

RN

NC S

RMe

Me N

NC

R

RMe

Me Ra: Meb: Etc: i-Pr

THF, 80oC

18 19

-K2S

50H.-W. Wanzlick, E. Schikora, Angew. Chem. 1960, 72, 494.

Stable Carbenes: Early Studies

Hans-Werner WanzlickBerlin

51

NC

N

Ph

Ph

HN

CN

Ph

Ph

KOtBu-KX, HOtBu

H. W. Wanzlick, H. J. Schönherr, Liebigs Ann. Chem. 1970, 731, 176H. W. Wanzlick, H. J. Schönherr, Chem. Ber. 1970, 103, 1037.

N

NC

Ad

Ad

HN

NC

Ad

Ad

NaH, cat. DMSOthf, -NaCl, -H2

A. J. Arduengo III et al. J. Am. Chem. Soc. 1991, 113, 361.

NiPr

iPr NC

iPr

iPr

R. W. Alder et al, Angew. Chem. Int. Ed. Engl. 1996, 35, 1121.

N

NC

Ad

Ad

6π Arduengo 11

Alder 16NiPr

iPr NC

iPr

iPr

H LDA, thf-LiCl, -DA

Cl–

Cl–

Wanzlick 170X–

Synthesis of Stable Carbenes…

52

Alkylation of Ethylene Thiourea- A Literature Review

J. F. Baer, R. G. Lockwood, J. Org. Chem., 1953, 76, 1162-1164.

R. N. Boyd; M. Meadow,Analytical Chemistry, 1960, 32, 551-554.

R = Me, Et, iPr, nPr, nBu, sBu, n-Hexyl, n-Heptyl, allyl, BenzylX = Cl-, Br-, I-

NH

C

HN

S

R

NH

C

HN

S + RX

X

NaOH

N

C

HN

S

RMeOH

60 - 0%1 1

NH

C

HN

S

NC

HN

S

CNHN

S

2HBr

Br

Br+ NaOH

NC

HN

S

CNHN

SMeOH

72%

1

20

53

ChemNMR C-13 EstimationChemNMR C-13 Estimation

Chemdraw : 13C-NMR Predictions

Experimental :

Predictions of different compounds

N

NS

N

NS

68.4

N

NS

N

NS

60

N

N

S

OH

3.57

3.57

2.47

5.69

2.0

N

N

S

N

NS

O

3.57

3.57

2.47

5.53

3.57

3.57

2.47

5.53

N

N

S

N

N

S

19.7

54

Yield: 95%m.p. : 183.5-184 ˚C

Yield: 40%m.p. : 181-183 ˚C

Synthesis of Bis-thiourea (Stoichiometry)

N

N

S

OH

3.57

3.57

2.47

5.69

2.0

N

N

S

N

NS

O

3.57

3.57

2.47

5.53

3.57

3.57

2.47

5.53

NH

N

S

CH3

2.4 CH2=O

N

N

S

N

N

S

CH2

CH3

CH3

2 +

Dioxane

ref.,6 hr

Dioxane

ref.,6 hrNH

N

S

CH3

1.2 CH2=O

N

N

S

N

N

S

CH2

CH3

CH3

2 +

55

Formation of imidazolidinium bromide

NCH2

N

R

R'

NC

N

R

R'

H

HCBr3 Br

CBr4

NC

N

R

R'

HBr

-HCBr3

NCH2

N

R

R'N

N

R

R'

H2 + H2 + 2e-

CH2RN RN H + H2 + 2e-

N-alkyl-1,4-dihydropyridine

56

Strategy for synthesis the diamino carbenes I

NH

NH

R

R'

NH

NH

R

OH

N

CH2

N

R

R'

N

CHBr

N

R

R'

N

C

N

R

R'

S

N

C

N

R

R'

R'NH2

SOCl2

(CH2O)n

CBr4

?

K

Pd, -H2

S8

? ?

-H2S

57

Synthesis of thiourea from imidazolinium salt (Arduengo salt)

G.B. Ansell, D. M. Forkey, D. W. Moore, J. Chem. Soc. D., 1970, 1 56b-57l

N

CH I

N

Me

Me

N

N

Me

Me

-H2CO3

- K2I

S

1. K2CO3/ MeOH2. S8, ∆

73 74

58

Synthesis of imidazolidinium bromide

NH

NH

R

R'

NCH2

N

R

R'N

N

R

R'

CBr4H . CBr4

Br-

(CH2O)n

Ether reflux, 20h

R, R'

MeEti-Prt-Bu

-CHBr3

sublimation

CBr4 crystalls

N

N

R

R'

HBr-150 ˚C

Brown residue

Recrystallization

from CHCl3 N

N

R

R'

HBr-

Colorless crystalls

m.p.=165-168 ˚C

194-195 ˚C 196-197 ˚C

Inclusion compound

59

Crystal structure of imidazolinium Br salt (inclusion)

60

Synthesis of thioureas by imidazolidinium salt

NCH Br

N

R

R

+ K2CO3 + S8

MeOH

∆ N

N

R

R

SR

a: Med: tBu

NCH Br

N

R

R

+ KOH + S8

MeOH

∆ N

N

R

R

S

Stronger base?Different solvent?

61

Dehydrogenation of imidazolidines: potential way to Wanzlick carbenes

NH

C:

HN

+H2

NH

CH2

HN

NC:

N

tBu

tBu

+ H2

NCH2

N

tBu

tBu

NC:

N

Me

Me

+ H2

NCH2

N

Me

Me

B1B956-31G(d)

CBS-Q

-21.94 -22.62

-20.36 -18.72

B98631Gd

-19.69

B3LYP631Gd

-22.3023.44

-19.38

-15.59-13.78

Reaction

Hydrogenation energies (∆Go , kcal.mol-1)

62

Transfer hydrogenation (computational study)

H2C CH2 + H2 H3C CH3

+ H2

-28.35 -23.28

-20.73 -18.64

-29.19

-21.67

-26.78

-18.98

B1B956-31G(d)

CBS-Q B98631Gd

B3LYP631GdReaction

Hydrogenation energies (∆Go , kcal.mol-1)

Hydrogen acceptor

NC:

N

tBu

tBu

+ H2

NCH2

N

tBu

tBu

-15.59-13.78

∆G0= -6.95

Hydrogen donor

63

Transfer hydrogenation (Experiments)

65d 67d

+

NCH2

N

tBu

tBu

Pt, C6D6

NC:

N

tBu

iPr

+

NC:

N

tBu

tBu

NCH2

N

tBu

iPr

190 ˚C

65c 67d 67d 65c

+N

CH2

N

tBu

tBu

Pd , toluene+

N

C:

N

tBu

tBu

190 ˚C

64

From Poly-Thioureas To Poly-Carbenes

• Carbene complexes

• New Homogenous Catalyst

• Electrochemical storage (Battery without metal)• Strong organic reducing agent• Carbene Complex

N NR

C

N N

C

R

N NR N N R

N NR N N R

Dimerization ?

N NR

C

S

N N

C

S

R

K/ THF

65

Dimerize for R < tBuReversibel at T > 160 oC

Denk & Hatano 1996

Enetetramines: Reducing agents

Do not Dimerize at all(not even for R = Me)

Arduengo 1991+

NC

NR

RN

N

N

NR

R

R

RN

CNR

R

Equilibrium at r.t. E. Hahn 1999

N

NN

N

N

N

CH3

CH3

CN

N

CH3

CH3

C

CH2 10.5 eV

NN GeMe3Me3Ge 5.87 eV

5.95 eV

6.06 eV

Reducing agent 1 IP (eV)

CH2

NC

N

CH3

CH3

N

N

N

N

CH3

CH3

CH3

CH3

2

66

67

N

N

N

N

bis(3-methylimidazolidin-1-yl)methane

S

S

bis(3-methyl-2-methyleneimidazolidin-1-yl)methane

N

N

S

1,3-dimethylimidazolidine-2-thione

N

NN

N

bis(3-methylimidazolidine-2-thione-1-yl)methane

N

CH2

N

1,3-dimethylimidazolidiniumbromide

68

quinone

O O

adamantyl

C•

guanidine

NH2

NH2

HN

69

Magnetic Properties of 15N, 14N, 13C and 1H isotopes

Magnetic properties of the 14N, 15N, 13C, 1H isotopes.

Nucleus Natural

abundance %

I

Spin

Relative

sensitivity

1H 99.98 1/2 1

13C 1.11 1/2 1.76 × 10 -4

14N .63 1 1.00 × 10 -3

15N 0.37 1/2 3.52 × 10 -6

• 15N is 283800 times less sensitive than 1H NMR !!!

• 14N has higher sensitivity than 15N but it is quadropolar and

has broad peaks.

70

Singlet-Triplet Gaps for Carbenes (kcal/ mol)Singlet-Triplet Gaps for Carbenes (kcal/ mol)

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.

• 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

Exp.

OC:

9.05a -56.6a

-56.9

-14.7a

-15.6 -139.6

NH

C :

HN

NH

C :

HN

8.1 -21.0CBS-Q c

CBS-APNO c 9.0

-86.5

G3 c 9.5

W1 c 9.2

H

HC:

F

HC:

F

FC:

Cl

ClC:

H2N

H2NC:

-55.3-21.0 -56.1

-72.9-55.9

-138.0-72.4 -85.3-14.5

-14.5

Triplet Singlet

71

13C-NMR (ppm)/ Electronic Stabilization

• Carbenes have highly deshielded carbon NMR shift• Unstabilized H2C: may serve as a refrence point for the high electronic stabilization of other carbenes

FC

F FC

F

F C

F

F

F

nTeflon

NC

N

iPr

iPr

NC

N

iPr

iPr

iPriPr N

CN

iPr

iPr

205.9

236.8 255.5 300.87 *

F

HC

H

1483.88 *

NC

N

Mes

Mes

244.5

SC

N

Ph

254.3

Aryl/ Alkyl

Nitrogen / Sulfur

Rings / Chains

Aromaticity

CF

* Computational data( CBS-APNO) Experimental data