Synthesis, DelocPlization and Reactivity in Stable Diaminocarbenes

Shilpi Gupta

A thesis subrnitted in conformity with the requirements for the degree of Master's of Science Graduate Department of Chemistry

University of Toronto

@ Copyright by Shilpi Gupta (1 999)

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Synthesis, Delocalbtion and Reactivity of Stable Dmrninocarbenes Master's of Science, 1999 Shilpi Gupta Department of Chemistry, University of Toronto

Abstract

The synthesis and reactivity of stable diaminocarbenes has been investigated. The

synthetic routes utilized were reductive dehydrosulhuization of tetra-substituted thioureas and 1,l-

elimination of HCI frorn carbenium salt, [N2CH]+ CI-. Synthesis of sterically crowded thioureas

suffers from low yields. The dehydrosulfurization of aminals has been discovered as a new one-

step synthesis for thioureas and carbenium salts.

Dehydrosulfurization was also investigated for urotropin and 1,3,5-trialkyl-hexahydro-

sym-triazines (investigated as precursors for polycarbenes). The dehydrosulfurization of sym-

triazines gave ring degradation products and [C2H2(NR)2CH]+ SCN-. Reaction of carbenes and

analogs with alcohols and alkoxides was investigated. The aromatic 61r-delocalization in carbenes

and related heterocycles was studied at the RHF 1 6-3lG* and B3LYP / 6-3 IG* level. The

obtained Lowdin bond orders correlate with the aromatic ring cument (IH-NMR) making them an

excellent computational tool to study the extent of ammatic delocalization.

- Table of Contents - A bstrac t

List of Tables

List of Figures

Ab breviations

Acknowledgments

Chapter 1

1.1

1.1.0

1.2

1.3

1.4

Chapter 2

2.1

2.1.1

2.1.2

2.1.3

2.2

2.3

2.4

2.4.1

2.5

2.5.1

2.5.2

2.5.3

Introduction

Carbenes and Carbenium Ions

S ynthesis

Oxidative Addition of Alkoxides and Alcohols

Metal-Carbene Complexes

Thioureas and Thiourea Derivatives

Results and Discussion

Dehydrosulfurization of Arninals (RzN)2CH2 with Sa

Applications of Thioureas

Objectives

Mechanism and Product Distribution

l=S via [l-R] CI

Synthesis of 3=!3

Synthesis of Imidazolium Salts

Deprotonation of [l-H] CI to give 1

Properties of Imidazolium Salts

Basicity of Carbenes and Acidity of Imidazolium Salts

Ion pairing

Hy bridization

ii

vii

viii

xi

xii

Solubilities of Carbenium Salts

Deprotonation Strategy to give 2 from [2-H] SCN

Deprotonation Strategy to give 3 from [3-LI] SCN

Other Deprotonation Bases

Aromatic, Anti-Aromatic and Linear Conjugated

Pol ycarbenes

1,3,S-tn-te~-butyl-hexahydro-sync-triazine with S8

Multistep approaches for the synthesis of Il-'Bu

1,3,5-tri-terr-butyl-hexahydro-sym-trimine and conformations

in other 1,3,5-triazines

Dehydrosulfurization of Urotropin

Reaction of Carbenes and Carbene Analogs with Alkoxides

and Alcohols

Reactions of Carbenes with Alkoxides and Alcohols

Reactions of L'Si: with Alkoxides and Alcohols

Reactions of LGe: with Alkoxides and Alcohols

Synthesis of 1-Hz

Reaction of 1 with Fe(C0)s

Reaction of 2 with Fe(C0)s

Aromatic Delocalization in Stable Carbenes: Correlation of

Experimental and Computational Data

Introduction

Vibrational Data as Criterion for Aromaticity

Delocalization of Carbene Derivatives

HOMO-LUMO Gaps

Structural Investigation of Carbenes and Protonated Carbenes

The Basicity of Diaminocarbenes

Chapter 3

3 .O

3.1

3.2

3.3

3.4

Carbenium Cations as Ionic Liquids

Conclusions and Future Goals

Experimentd 86

General Experimental 87

Synthesis of 2=!3 88

Synthesis of l=S via [1-H] CI 9 1

Attempted Synthesis of 3=S 92

Dehydrosulfurization of 1,3,5-tn-terf-buty l-hexahydro-sym- 95

triazine

Synthesis of 13-Hl SCN

Synthesis of [1-H] Cl

Proton Transfer Reactions (NMR Scale)

[1-H] Cl with D20

[LH] Cl with 2

[2-H] SCN with 1

[3-Hj SCN with 1

[l-Kj Cl with [3-HJ SCN

Synthesis of 1

Synthesis of 2 from 12-81 SCN

Attempted Synthesis of 3

S ynthesis of 1,3,5-tn- te^-butyl-hexahydro-sym-triazine

Synthesis of 1-Hz

Preparation of tert-butoxy lithium

Attempted Synthesis of L'Si-(0tBu)Li

Appendix 1

Appendix 2

Appendix 3

Attempted Synthesis of LGe-(0tBu)Li

Attempted Synthesis of 1-(OtBu)Li

Attempted Synthesis of 2-(OtBu)Li

Attempted Synthesis of L'Si-(0tBu)CI

Attempted Synthesis of L1Si(0tBu)2 with BuOLi

Attempted Synthesis of L'S~(O~BU)~ with 'BUOH

Attempted Synthesis of L'Si(0Me)z

Attempted Synthesis of L'Si-(0tBu)H

Attempted Synthesis of LGe-(0tBu)H

Attempted Synthesis of 1-(0'Bu)H

Attempted Synthesis of 2-(0tBu)H

Synthesis of 2-(0Me)H

Preparation of tert-butoxy copper

Attempted Synthesis of L'Si-(OtBu)Cu

Attempted Synthesis of 1=Fe(C0)2

Attempted S ynthesis of 2=Fe(C0)2

X-ray Crystal Structure Data

References

A bbreviations of Compounds

List of Tables

Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8

Table 9

Table 10 Table 11 Table 12 Table 13 Table 14 Table 15

Table 16

Table 17 Table 18

Table 19

Table 20

Table 21 Table 22 Table 23 Table 24 Table 25 Table 26

Thioureas in medicine Influence of different reaction conditions on 2=S, 12-HJ SCN fomation Influence of different reactions on 3-C, 3=S, [3-Hl SCN formation Influence of counter ion and aromaticity on chernical shifts

% s character in C-H carbon of carbenium salts Solubilities of carbenium salts Sublimation fractions for deprotonation of [2-H] SCN with LDA Sublimation fractions for dehydrosulfurization of 1,3,5-tri-tert-butyl-

hexahydro-sym-triazine ( 140 OC, 26 h) Sublimation fractions for large scale dehydrosulfurization of 1,3,5-tri-te+ butyl-hexahydro-sym-triazine(150 OC,58h) Conformations of hexahydro-sym-triazines Summary of reactions of 1,2, L'Si:, LGe: with alkoxides and alcohols Increasing delocalization as obtained from computational IR frequencies Correlation between bond order and NMR data Correlation between Eg and aromatic stability Correlation between computational IR frequencies and Eg for carbenes and it's derivatives Normal modes, Eg, bond orders, and experimental NMR data of selected diazoles Normal modes of selected 1,l-dihydro- 1,3-diazoles Comparison of experimental and calculated structures of L'CH+ cations using B3LYPl6-3 IG*, W/6-3 lG*, MW6-3 le*, and AM 1 methods Comparison of experimental and calculated structures of LCH+ cations

using B3LYP16-3 L G*, HF/6-3 le*, MP2/6-3 1 G*, and AM 1 methods Comparison of experimental and calculated structures of 1 cations using B3LYP/6-3 lG*y HFl6-3 lG*, MP2f6-3 lG*, and AM1 methods Calculated tme energies &cal) for carbenes and derivatives Sublimation fractions for Method A Sublimation fractions for Method B Sublimation fractions for Method C Sublimation fractions for 1-C formation Sublimation fractions for 3-H2:S8 (1 : 1/4)

vii

List of Figures

Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Fipre 18 Figure 19 Figure 20 Figure 21a Figure 21b Fipre 22 Figure 23 Figure 24a Figure 24b Figure 25 Figure 26a Figure 26b Figure 27 Figure 28 Figure 29 Figure 30 Figure 31

Hydrolysis of chlorofom

Representation of electronic structure of carbenes

Arduengo's carbene

Aromatic divalent carbenes la and lb and non-aromatic carbene 2 Synthetic strategies to obtain diaminocarbenes via a carbenoid

Reaction scheme for silylenoid species formation Synthetic strategy for a-haloorganolithium species

Reaction scheme for carbenoid synthesis

First transition metalcarbene complex

Geometrical positions of the carbene ligand Attempted synthesis of l=Fe(C0)2 General equation for the synthesis of carbene from thiourea Literature methods to obtain thiourea General reaction scheme for the synthesis of thioureas from arninals

Synthesis of the first thiourea Tautomerism in thioureas

Synthesis of cyclic thioureas Thiourea derivatives as vulcanization accelerators

Synthesis of 2=S from CS2/pylI2 method ORTEP view of [2-Hl SCN Possible mechanisms for the oxidation of arninals Possible reaction schemes I,II,III for the sulfurization of aminals Synthesis of 2=S from dehydrosulfurization of 2-Hz with Se Synthesis of l=S from 1 in a one-pot reaction Possible sulfur containing heterocyclic compunds Possible structure of the 100-125 O C fraction: "Zwitterion" formation

Synthesis of 3=S 1H NMR of sublimate at 150 O C (3=S) 1 3 ~ NMR of sublimate at 150 OC (3=S) ORTEP view of 3-C ORTEP view of [3-II] SCN Synthesis of [l-8] CI from glyoxal Attempted synthesis of [l-tI] CI fiom diazadiene ORTEP view of [l-HJ CI

Fipre 32 Figure 33 Figure 34 Figure 35 Figure 36 Figure 37 Fipre 38 Figure 39 Figure 40 Figure 41 Figure 42 Figure 43 Figure 44 Fipre 45 Fipre 46 Fipre 47 Figure 48 Figure 49 Figure 50a

Fipre 5Ob Figure SOC Figure 51 Figure 52 Figure 53 Figure 54 Figure 55 Figure 56 Figure 57 Figure 58 Figure 59 Figure 60 Figure 61 Figure 62 Figure 63 Figure 64

Synthesis of 1 by deprotonation of [1-Hl CI ORTEP view of 1 Deuterium exchange reaction of [1-A] CI Proton exchange between [1-Hl CI and 2 Proton exchange between (2-Hl SCN and 1 Proton exchange behueen [3-Hl SCN and 1 Proton exchange between [l-Hl CI and [3-H] SCN Deprotonation of [2-H] SCN to give 2 Deprotonation of [3-A] SCN to give 3 1H NMR of 80-90 O C fraction (3) Structure of 3-CHO Reaction of SCN- with nBuLi Reaction schemes for [3-H] CI formation Delocal ized pol y -car benes Synthetic strategies for tris-carbene Synthesis of Il-Me Decomposition products of the reaction of 9 with S8 ORTEP view of [l-Hl SCN Reaction scheme for the dehydrosulfurization of 1,3,5-tri-tert-butyl-

hexahydro-sym-triazine Possible sulfur-exchanp reaction between 9 and 15 13C NMR simulation of mono-, bis-, tri- substituted thiourea Attempted synthesis of 16 Synthesis of 1,3,5-tn-tert-buty l-hexahydro-syrn-triazine Graphical representation of melting point of 9

Synthesis of methylurotropinium thiocyanate

ORTEP view of [5-CH31 SCN Decomposition of halogen-substituted carbene species to carbenoid Reductive elirnination of aicohols

Synthesis of 2 - ( 0 t ~ u ) ~ i Reaction of 1 with tBuOLi Reactions of 1,2, LGe: with tBuOH Synthesis of 2-(0Me)H using 1: 1 ratio of 2 to MeOH ORTEP view of 24330 Attempted synthesis of L'Si-(0tBu)Cu Attempted synthesis of L'Si-(0tBu)Li

Figure 65 Figure 66 Figure 67 Figure 68 Figure 69 Figure 70 Figure 71 Figure 72 Figure 73a Figure 73b Figure 73c Figure 74 Figure 75

Attempted synthesis of L'Si-(O*Bu)CI Attempted synthesis of L'Si-(0'Bu)H Attempted synthesis of LGe-(O%)Li Synthesis of 1-H2 Synthesis of a bis-carbene complex q 1 complex formation: l=Fe(CO)4 Attempted synthesis of 2=Fe(CO)4 The stable carbene 1 and it's derivatives Reaction between L'CH+ and LC: Reaction between L'CH2 and LC: Reaction between L'CH2 and L CH+ General representation of ionic liquids Ionic liquids and Carbenium Salts

THF Et20 HMPA TMS Me nPr fBu Et iPr PY GCMS IR NMR h d A equiv mm01 Ph Et3N PES CDC13 C6D6 D2O PP=' r. t. t~ mins. Ca.

SYm asym

tetrafiy drofuran diethyl ether hexarnethylphosphoric triamide teuamethy lsilane methy l n-propy i tert- buty 1 ethy 1 iso-prop y l pyridine gas chromatography 1 mass spectrometry in fra-red nuclear magnetic resonance hour(s) day (s) heat equivalent miili mole(s) pheny 1 triethy lamine photo electron spectroscopy deuterated chlorofonn deuterated benzene deuterated water parts per million room temperature retention tirne minutes approximatel y symmetnc asymmetric

Acknowledgments

1 would like to begin by thanking my supervisor, Prof. Michael K. Denk, for his

continuous support, guidance and encouragement over the past twenty months and for giving me

the opportunity to work on some really stimulating projects. 1 like to thank rny CO-workers, past

and present (Ken, Sébastien and Jose), for making the lab a pleasant place to work in. Thanks aiso

goes to al1 the volunteers in the lab, especially, John and Neeti, for keeping up with me when 1 got

so very frustrated.

1 am grateful to Dr. Alan Lough for his keen interest and patience in obtaining those

beautiful X-ray structures. My sincere gratitude gws to the lab technicians, Sarnia and Pam, for

al1 those srniles and for being there for me. Thanks also goes to Dr. Tim Burrow for his advise on

some NMR experiments, and to Dan Mathers and Dr. Alex Young for mass-spectral work.

Lastly, but definiteiy, not the least, 1 like to thank my parents who have k e n my backbone

every single moment. Words fail to express how deeply grateful I am for the unconditional love

and moral support they have given me every single day.

xii

Chapter 1: Introduction

1.1 Carbenes and Carbeniwn Ions

Carbenes are highly reactive species (lifetimes under 1 sec); the parent species being

CH2 (methylene). The concept that carbenes might play a significant role as reactive

intermediates dates back to the early kinetic investigations of Hine who postulated the

intermediacy of C12C: in the hydrolysis of chloroform (Fig. 1) [ 11.

- OH . fast

CCI2 - CO + HCO; H20

Fig. 1. Hydrolysis of chlorofon

Methylene has been the subject of the now classical spectroscopic studies by Herzberg's

group [2]. Unlike most other carbenes, methylene has a triplet ground state, but the singlet state

is only slightly higher in energy.

The diaminocarbenes la and 2 al1 have a singlet ground state (Fig. 2). The singlet state

of carbenes with it's empty p-orbital is isoelectronic with carbocations and is stabilized more by

conjugation than the triplet state which has a singly occupied p-orbital [3].

Triplet state Singlet state

Fig. 2. Representation of electronic structure of carbcnes

A number of carbenes have been isolated in frozen matrices and investigated

spectroscopically [4]. Carbenes have been the subject of many computational studies. Most of

the older results are now obsolete as a result of better and better experimental data and new

computational data [4]. The extreme reactivity of carbenes made the goal of obtaining stable

15

carbenes seem futile, although early studies by Wanzlick claimed that diaminocarbenes can

persist in solution and at rwm temperature for prolonged periods of time.

In 1964, Wanzlick proposed that enetetramines can dissociate into diaminocarbenes but

was unable to present unambiguous proof for the presence of free carbenes 151. The goal of

obtaining stable carbenes was finally realized in 1991 when Arduengo et al. described the

synthesis and structure of 1,3-Di-adarnantyl-irnidazole-2-ylidene, the first unambiguously stable

carbene [6a-il.

Arduengo's carbene

1 ad

Fig. 3. Arduengo's carbene

Many other studies have since appeared on the subject of diaminocarbenes from

Arduengo's group [6]. The question if diaminocarbenes require steric and electronic stabilization

or just electronic stabilization was answered by Our study of the corresponding saturated

systems. [7].

This study addresses a number of controversial or unexplored aspects of the chemistry of

stable diaminocarbenes. This thesis c m be grouped around the subjects:

Synthesis

Aromatic defocalization

Reactivity

New Topologies

16

1.1.0 Synthesis

Arduengo's published procedure for the synthesis of stable carbenes requires the

deprotonation of irnidazolium salts with NaH in DMSO 161. This rnethod is inconvenient for the

large scale reaction and is aiso unsuitable for the synthesis of volatile carbenes because of the

separation from DMSO. The use of DMSO is thus problematic for a general and a specific

reason:

DMSO is not easy to purify and very hygroscopic.

For volatile carbenes, such as 1 and 2 (Fig. 4), the removal of a high boiling solvent like

DMSO (bp = 189 OC) will inevitably lead to the loss of much of the formed carbene.

As demonstrated in this thesis, the deprotonation of the imidazolium salt [l-Hl Cl with

"BuLi in THF is a simple alternative. Separation of the carbene 1 from LiCl formed in the

reaction was no problem and the carbene is easily isolated by sublimation in Ca. 72 % isolated

y ield.

R R R I I I (2.: R = adamantyl cN): - @,E: mesityl N N

I met hyl

I R R

I R

iso-propyl t e s bu ty 1

1 a l b 2

Fig. 4. Aromatic divalent carbenes l a and l b and non-aromatic carbene 2

The synthesis of the imidazolium sdts was achieved in a patented three-component

condensation from glyoxal, a primary amine and formaldehyde. The synthetic details are

sketchy and the reactions as described are laborious. No proper purification and work up

procedures are given. This thesis descnbes a simplified procedure for the synthesis of the

imidazolium salts and two new methods for obtaining the thiocyanate salts.

17

The fact that diaminocarbenes can be obtained by deprotonation of imidazolium salts

raises the question of how basic diaminocarbenes reaily are. This question was investigated by

computational methods and by the study of proton exchange equilibria. The deprotonation of

imidazolium salts with "BuLi and other organometallic bases can take place by two different

pathways.

Fig. 5. Synthetic strategies to obtain diaminocarbenes via a carbenoid

These are, general deprotonation that would lead directly to the carbene (route a) or

metallation that would imply the intermediacy of a carbenoid (route b) (Fig. 5).

Carbenoids were postulated as intermediates by Witîig et. al. in 1941. According to G. L.

Closs and R. A. Moss, a carbenoid is a species that is responsible for electrophilic reactions

instead of a carbene (81. The terni is used pnmarily to characterize a type of mechanistic

behavior and compounds in general that have a metal atom and an electronegative leaving group

on the sarne carbon atom.

1.2 Oxidative Adclition of Alkoxides and AlcohoIs

Analogous to carbenoids, (alkoxysilyl)lithium compounds having alkoxy groups have

been described by the group of K. Tamao (Fig. 6) [9].

@ \ ,Nu Nu - Si, ' Li Fig. 6. Reaction scheme for silylenoid species

The possible stability of carbenoids N2CLi-OR and N2CCu-OR was investigated by

reacting carbenes N2C: with Li-Alkoxides and Cu-Alkoxides as well as alcohols. Silylenes and

germylenes were likewise investigated. Reactions of carbenes 1 and 2. and germylene, LGe:

with tBu0Li (Fig. 7) and 'BuOCu failed to give the corresponding alkoxy species excepting

silylene, L'Si:. In the case of the addition of alcohols, addition was observed for L'Si:, and

carbene 2.

'Bu 1

'BU I

N I

E = C, Si, Ge

Fig. 7. Synthetic strategy for a-haloorganolitùium species

a-haloorganolithium compounds 1.2A are themally unstable (Fig. 8) [ 1 O]. They are

reactive since the heteroatom works as a leaving group.

1.2A

Fig. 8. Reaction scheme for carbenoid synthesis

1.3 Metnl-Carbene Complexes

The first synthesis of a transition metalsarbene complex 1.3A (Fig. 9) by E. O. Fischer

and A. Maasbol in 1964 opened the gates of organometallic research, such as, in organic

syntheses and catalytic reactions [ 1 I l .

Fig. 9. First transition metal carbene complex

In ail (C0)4Fe(carbene) complexes whose structures are known from diffraction studies

or spectroscopy, the carbene ligands are good donors but poor s-acceptors because of one or

two a-substituents having lone pairs. The carbene ligand always occupies the apical position

(1.3B and 13C), with it's orientation determined by stenc factors (Fig. 10). This is in accord . with a theoretical andysis on site preferences for transition metal penta-coordination [ I l ] .

1.3B 1.3C

Fig. 10 Geometrical positions of the carbene ligand

In this thesis, the reaction of the diaminocarbenes 1 and 2 with Fe(C0)s was

investigated. The X-ray structure could not be obtained as the product (yellow, powdery) did not

20

crystallize even after layering or by heating the sublimed product under reduced pressure. The

presence of a carbene complex was concluded from NMR (lH, 1 3 ~ ) and Fî-IR spectroscopy.

Solubility problems and synthetic aspects are discussed.

ncat

?

1 1 =Fe(CO)2

Fig. 1 1. Attempted synthesis of 1 =Fe(CO).L

1.4 Thioureas and Thiourea Derivatives

Thioureas are used in the pharmaceutical sector, in plant protection, in various technical

applications, and in the synthesis of heterocycles [12]. In the context of this study, we were

interested in thioureas as starting materials for the synthesis of stable carbenes.

Fig. 12. General equation for the synthesis of carbene h m thioureû

The synthesis of the parent compound, thiourea NHz-C(S)-NH~ from calcium

cyanamide is straightforward and is the bais of the current technical process (SKW, Germany).

A number of different methods are available for the synthesis of thioureas bearing substituents

on nitrogen (361. Thiourea is not a good starting material for the synthesis of its N-substituted

derivatives because electrophiles react with the sulfur in most cases. A closer examination of the

synthetic repertoire reveals serious deficiencies:

21

The methods described in the literature are generally incompatible with bulky substituents

on the nitrogen atoms. For example, compound 4 (Fig. 13) could not be prepared by known

methods in yields higher than 1

yield - 70 60 50 18 a

a) yield without 12 = O %

Fig. 13. Literature methods to obtain ihiourea

Existing methods typically use the highly toxic and extremely flammable carbon disulfide or

the toxic and expensive isothiocyanates R-N=C=S as starting materials.

The standard synthesis of thioureas from isothiocyanates and amines is restricted to the

synthesis of RI-NH-C(S)-NR*R~.

This thesis presents a new synthesis for diaminocarbenes, thioureas and stable carbenium

cations. The carbenes are obtained by the reductive dehydrosulfurization of tetra-substituted

thioureas and I,l-elimination of HCl from carbenium salt, [N2CH]+ CI-. The thioureas and

carbenium salis are obtained by the subsequent reaction of amines with formaldehyde and

elemental sulfur. The reaction of the aminals R ~ R ~ N - C H ~ - N R ~ R ~ with typically 114 molar

equivaleni of Se takes place readily between 150 - 180 OC and leads to the formation of thioureas in modest yields with the major products being the carbenium saits, [N2CH]+ SCN-.

Fig. 14. General reaction scheme for the synthesis of thioureas via aminais

22

The carbenium cation thiocyanates were converted into the carbenes. However,

sublimation work up leads to a broad spectnim of decomposition products (1H NMR).

Chapter 2: Results and Discussion

24

2.1 Dehydrosulfurization of Aïninais (Rm2CH2 with Sa

Thiourea was first prepared by Reynolds by thermal rearrangement of ammonium

rhodanide at Ca. 150 OC (Fig. 15) [Ml.

NH4SCN (NHù2CS

Fig. 15. Synthesis o f the first Thiourea

The reaction between carbon disulfide and amrnonia or ammonium carbonate under

pressure at Ca. 140 O C has not achieved industrial application [14]. Thiourea has three functional

groups: arnino, imino, and thiol. This results from tautomerism between thiourea and isothiourea

(Fig. 16).

Thiourea Isothiourea

Fig. 16. Tautomerism in thioureas

Because of this polyfunctionality and also because of its complex-forming properties,

thiourea has been widely used for more than 30 yean mainly as starting material for nitrogen-

and sulfur-containing heterocycles and formamidinesulfinic acid, as a reaction partner for

aldehydes, and as a component of addition cornpounds and complexes [ 15-19].

Cyclic thioureas have been obtained by the methods known for open-chah thioureas,

and by the reaction of diamines with thiourea [20].

Fig. 17. Synthesis of cyclic thioureas

25

2.1.1 Applications of Thioureas

Thioureas have a wide range of uses, e.g. for producing and modifying textile and

dyeing auxiliaries [2 1, 221, in the production and modification of synthetic resins [23], in repro

technology [24], in the production of pharmaceuticals (sulfathiazoles, tetramisole [25], and

cephalosporins [26], in the production of industriai cleaning agents (e.g., for photographic tanks

[27], and metal surfaces in general [28. 29]), for engraving metal surfaces [30], as an

isomerization catalyst in the conversion of maleic to furnaric acid [3 11, in copper refining

electrolysis [32], in electroplating (e.g., of copper) [35]. and as an antioxidant (e.g., in

biochemistry) [36]. Other uses are as an additive for slurry explosives [35], as a viscosity

stabilizer for polymer solutions (e.g., in drilling muds [36]) and as a mobility buffer in

petroleum extraction [37]. The removal of mercury from waste water of the chlorine-alkali

electrolysis process is possible with thioureas [38]. Thioureas can also be used to extract gold

and silver from minerals [38,39].

Vulcanization accclcmtor,

H

Fig. 18. Thiourea derivatives as vulcanization accelerators

The N-substituted thioureas, that we are investigating, may find use as accelerators for

the vulcanization of polychloroprene and ethylene-propylene-diene terpolymers (EPDM) 1401

(Fig. 18, Table 1).

I Compound Use

thyrotherapeutic agent (th yreostatic)

thyrotherapeutic agent (thyreostatic)

thyrotherapeutic agent (thyreostatic)

ultrashort general narcotic, anesthetic

propy lthiouraci 1 :

rnethylthiouracil

thiamy ta1 a

Table 1 Thioureas in medicine

2.1.2 Objectives

Thiourea 2=S was initially obtained in our group from carbon disulfide / 12 / pyridine:

Fig. 19. Synthesis of 2 5 h m CS2 1 py 1 12 method

27

However, this method suffen from the use of toxic and expensive pyridine and from low

yields (15-20 %). The objective is to directly convert aminals into thioureas using the one-step

dehydrosulfurization approach . This approach has the advantage that aminals form readily and in high yields even with sterically bulky secondary amines, especially if the reaction leads to

cyclic products. The reaction was investigated first for the Bu-arninal 2-H2 with elemental

sulfur because the desired product 2=S had already been obtained and hlly characterized from

2-C and CSz. Reaction of 2-Hz with S8 (no solvent) starts at 170 OC as evidenced by the color

change and gas evolution. The reaction gives only a small yield of 2=S. Investigation of the

sublimation residue showed that the main product (21%) of the sulfurization of 2-H2 is the

carbenium salt, (2-rn SCN. [&Hl SCN was characterized by single crystal X-ray diffraction

[data set, appendix I l (Fig. 20).

Fig. 20. ORTEP view with hydrogen atoms omitted for clarity. Thermal ellipsoids are at the 50%

probability IeveI. Seiected bond distances [pm] and bond angles [O] as follows: C(1)-N(1) 131.3(2),

C(1)-N(2) 131.4(2), N ( l W ( 2 ) 147.3(2), C(S)-C(3) 15I.7(3), N(2>-C(4) 149.2(2),

N(3)-C(12) 157.8, N(3)-H( IA) 4 14.6, C(2)-C(3) 15 1.7(3), N(3-(12)-H(IA) 14 1.43(O.S),

N( I)-C(I>-N(2) 1 13.80(16), C(1)-N(lW(2) 108.83(15), N(I)-C(2-(3) 102.47(16), H...(N)

24 l(2).

28

2.1.3 Mechanisrn and Product Distribution

The breaking of a C-H bond at the comparatively low temperature of 170 O C is

surprising and requires the proposal of an adequate mechanism. The strength of a typical C-H

bond mles out a direct homolytic fission. It is likely that the initial step of the reaction is the

oxidation of the aminal by a S radical (e. g. 'S-(S)6-S) to the mesomerically stabilized radical

L'CH;?]+' (Fig. Sla).

R-S IL 'BU

I

[;&H

I 'Bu

Fig. 2la. Possible mechanisms for the oxidation of aminals

The radical cation can now loose a proton or a H radical. Both processes are facilitated

by the fact that the cation and radical character of the nitrogen atom is partially delocalized into

the C-H bond via hyperconjugation (interaction of the nitrogen p-orbital with the C-H B*

orbital). The relative importance of the two steps cannot be evaluated with the data at hand. A

computational study is in progress. For al1 the investigated reaction conditions, both the thiourea

and the carbenium cation were fonned. Under the reaction conditions, the carbenium salts and

the thiourea were stable. This rules out the consecutive formation of one from the other (Fig.

21 b). A branching like the one invoked by the mechanistic hypothesis above offers a convenient

explanaiion of this expenmental obsetvation .

III

Fig. 21 b. Possible reaction schemes 1, II and II1 for the sulhization of minais.

Apart from a mechanistic insight, the variation of the reaction conditions had a synthetic

goal, narnely to maxirnize the yield of 2=S or [2-H] SCN. To this end, three different protocols

(A, B, C) were investigated: the amount of sulfur used is an obvious parameter to be studied.

2-H2 2-S 2-C (2-H) SCN

Fig. 22. Synthesis of 2=S h m dehydrosulfiirization of 2-Hz with S8

Method A restricts the arnount of sulfur to the stoichiometrically necessary lower limit

(1/4 equivalent). Method B uses one equivalent which corresponds to a four fold excess of

sulfur under otherwise identical reaction conditions.

Method A gave the highest yield of 2=!3 (15% ) apart from 12-H] SCN (2 1 %) and 2-C

(37 96). A mass loss of 1.85 g was unaccountable after adding up the weights of dl fractions of

the sublimed material.

In order to compare how the different reaction conditions influence the formation of

2=S, and [2-H] SCN, the weights and % yields of each of the corresponding fractions were

tabulated (Table 2).

.-

Table 2. Influence of different reaction conditions on 2=S and [2-Hl SCN formation

The dehydrosulfurization leads to the formation of H2S which in tum could react with

the arninal by protonation. It was therefore attempted to increase the overall yield by adding acid

scavengers. However, addition of K2C03 lowered the yields and gave a more complex product

spectmm as indicated by the 1H NMR of the crude reaction mixtures. The use of additives was

not pursued any further.

Increasing the amount of sulfur (Method B) leads to a decreased yield of both the

thiourea and the carbenium salt (10 %). It is noteworthy, that the thiourea isolated by

sublimation is now contaminated (contrast to Method A) by the unsaturated thiourea l=S and a

number of other compounds that were characterized only by their GC-MS traces. The total

combined weight of the thiourea fractions (7.00 g) exceeds the theoretically possible amount of

5.76 g. It must be concluded, that a substantial part of the volatile Fraction consists of elemental

3 1

sulfur and in fact the total amount of re-isolated sulfur could be as high as 75 1 (6.16 g) of the

total arnount at the beginning of the reaction.

The yield of [2-H] SCN cm be detemined and allows the conclusion that an excess of

sulfur is unfavorable for its formation. Method C is identical to Method A, but the reaction time

has now been increased from 1 h (A) to 30 h (C). This increases the yield of [2-H] SCN from 21

% (A) to 43 1 (C). This clearly demonstrates. that the formation of 12-H] SCN is a slow

process that must involve an unknown intermediate. The thiourea has been ruled out as

intennediate because it is stable under the reaction conditions.

2.2 l=S via [l-H] Cl

The formation of l=S under the given reaction conditions is the result of a

dehydrogenation reaction. Pure 2=S can be transformed into l=S by heating with elemental

sulfur at 170 O C for 18 h. This does not, however, give pure 1=S but always ieads to mixhires of

l=S and the starting material 2=S. Reaction of the stable carbene 1 with S8 in THF at r. t.

proved to be the only way to obtain pure 1=S (Fig. 23).

1 l=S

Fig. 23 Synthesis of I=S fiom 1 in a one-pot reaction

Reaction of 1 with Sg gave two volatile prducts ( 1 0 - 125 O C ) , l=S and a black micro

crystalline product. This black micro-crystalline compound was poorly soluble in benzene (5

g/L ) and gave colorless solutions in chlorofomi. This could be due to decomposition with

CDC13 or poor solubility. The IH NMR in CDClj showed signais at 6(lH, ppm): 1.56 (int. 14 ),

7.06 (d, kt. 1.5 ), 7.36 (int. 2.3), and 7.62 (int. 1).

32

These second set of signals can be tentatively ascribed to compounds of type 2.2A or 23B (Fig.

24a). In view of the volatility of the second component, structure 2.2A seems more likely.

2.2 A 2.2 B

Fig. 24a. Possible sultùr-containing heterocyclic compounds

The sublimation of the black cornpound between 100 -125 OC requires that the

compound has a low molecular weight. It is therefore surprising, that the compound is insoluble

in benzene. The color and solubility of the compound could point towards a zwitterion Z.

I I 'Bu 'BU

Fig. 24b. Possible structure of the 100-125 OC fraction: "Zwitterion" formation

2.3 Synthesis of 3=S

The attempts to obtain the thiourea 3-S analogous to 2=S from the corresponding

diamine 3-C and CS2 (boih with and without the addition of iodine) led to product mixtures and

insoluble and presumably polymeric materials.

The dehydrosulfurization strategy was tried instead. This approach was successfbl as

evidenced by the presence of the thiocarbonyl signal (185.3 ppm) in the I3c NMR spectrum, but large amounts of the 1,3-diamine and other unidentified / side products were fomed and the

thiourea could not be obtained in pure form.

3-Hz 3 5 3-C 13-Hl SCN

Fig. 25. Synthesis of 3=S

The dehydrosulfurization of 3-Hz differs from the analogous reaction of 2-Hz in three

important ways:

1. The required minimal reaction temperature is substantially lower for the six-membered

ring (1 10 OC) than for the five-membered ring (160 OC).

2. The amount of diamine formed in the reaction is rnuch higher in the case of the six-

membered ring than in the case of the five-membered ring.

3. The volatile fraction contains two additional compounds in substantial quantities for the

six-membered ring, while only traces of impurities were observed in the case of the five

membered ring.

The reasons for these differences are speculative and further variation of the ring size

and the steric bulk of the substituents (here: Bu) is clearly desirable. The formation of the

carbenium cation salt is favored by prolonged reaction times in both cases.

The number of 'Bu signals (4) in the NMR of the sublimate at 150 O C (Fig. 26a)

suggests the presence of 3=S (1.25 ppm, int. 6.5), J-C (1.12 ppm, int. 1) and two unidentified

side products (1.43 ppm, int. 1.4 and 1.60 ppm, int. 1).

Atso, the 13C NMR of the sublimate shows the C=S resonance at 185.32 ppm which is a

direct evidence for the presence of thiourea (Fig. 26b).

Fig. 26a. I H NMR in CDC13 of the sublimate ai 150 O C

Fig. 26b. I3c NMR in CDCl3 otthe sublimate at 150 O C

The yield of 3=S varies between 0% - 40% depending on the reaction temperature and reaction time (Table 3).

3-H2 : S8 3432 : Sa T [OC] crude 3-c 33s [3-H] S a [mols] [ml t[hl extract 9byields %yields % yields

[ m s l 1:l 1.89 : 2.44 150 3.8gi 2% 40% 122%~

13

Table 3. Influence of different reaction conditions on the formation of products: X, 3=S, (SHI SCN

this reaction was done in a sublimation f l u k and the crude mixture was the sum of the weighi of the yellow crystalline solid on the finger and a black solid at the bottom of the flask. The residue was a mixture of 3=S, [SHI SCN, 3-C and one other unidentified product. The weights of the fractions are measured from the relative intensities of the 'BU signals. ii this fraction is a yellow oil and the NMR shows a mixture of three different products with 3=S being the major product.

High reaction temperatures and long reaction times favor the formation of [3-Hl SCN;

low reaction temperatures favor the formation of 3-C; intermediate reaction temperatures ( 150

OC) favor the formation of 3=S. Attempts to confirm the formation of 3=S by an X-ray structure

led to the isolation and structural characterization of the 1,3-diamine 3-C instead (Fig. 27).

Fig. 27. ORTEP view with hydrogen atoms omitted for cliuîty. Thermal ellipsoids are at the 50%

probability leveI Selected bond distances [pm] a d bond angles [O] as follows: N(l)-C(l) 146.40(13),

C(1 W ( 2 ) 152.34(14), C(2)-C(3) 152.23(15), N(l)-C(4) 147.88(13), N(1 +C(1 )-C(2) 1 1 1.76(9),

36

Attempts to grow crystals of 3=S by sublimation (150- 160 OC) or crystallization (1 :2

mixture of CHC13 and hexanes) were unsuccessful. The sublimation residues consist of pure

carbenium sait 13-H] SCN. The sait is obtained in an overall yield of 34 % (reaction conditions:

190 OC / 40 h) and has been unambiguously characterized by single crystal X-ray

crystailography (appendix 1, Fig. 28).

Fig. 28. ORTEP view with hydrogen atoms ornitted for clarity. Thennd ellipsoids are at the 50%

probability level. Selected bond distances [pm] and bond angles [O] as follows: N(l)-C(I) 130.2(6),

C(2)-C(3) 139.7(7), S( l ) -C(7) 160.0(12), N ( l M ( 4 ) 146.6(7), C(1)-N( 1 ) -C(2) 1 16.0(5), N(1)-

C( 1 )-N( 1)#2 129.5( 10). C(3)-C(2)-N(l) 108.9(5), C ( 2 ) # 1 4 ( 3 j C ( 2 ) 24.7(4), H--(N) 394(5).

37

2.4 Synthesis of Imidazoüum Sdts from Glyoxai

The imidazolium salts are now of considerable interest as starting materials for the

synthesis of Arduengo carbenes [6h].They form easily from a primary amine, glyoxal,

formaldehyde and hydrochloric acid (Fig. 29). The reaction has so far (1998) only been

descri bed 'BU 'BU

'BUNH~ (2 eq.) ' c P I O 6NHCll24hA THF N

I 'BU

I 'BU

Fig. 29. Synthesis of [l-H] CI fiom glyoxal

in three patents [41a,b] that give no details on the synthesis, work up and purification. The

mechanism of this one-pot condensation reaction is also unclear.

The intermediate formation of the corresponding 1,4-diazadienes from the primary

amine and glyoxal was considered as a mechanistic possibility. It was therefore desirable to find

out if the imidazolium salts can be obtained directly from the diazadiene. Mixtures of 1,3-Di-

ter?-butyl-l,4-diazadiene, formaldehyde (35 % in water) and hydrochlonc acid in different

solvents did not produce any imidazolium salt and only shifts of diazadiene were present (IH

NMR).

Fig. 30. Attempted synthesis of (1-Hl CI Born diazadiene

It was therefore decided to establish the experimentai details missing in the patent. The

patent requires first the addition of paraformaldehyde to 6N HCl followed by addition of tert-

butylamine and finaily glyoxal.

38

M e r 24 h stimng at r.t.. the lH-NMR (CDC13) of the aqueous phase shows the signas

of [1-HICI (1.79, 7.45 and 10.0 ppm) and a second unidentified component (1.45 s, 4.99 m,

8.30 br., 9.75 br.) The signals of the unknown second component are in agreement with the

formation of [1-HJOH. An attempt to conven this "hydroxide" into the chloride with MqSiC1

failed, but the formation of 11-HJCI can be completed by heating the crude reaction mixture to

reflux for 24 h. The resulting dark brown viscous liquid was sublimed at 90-180 OC oil bath

temperature. The sublimate is a creamy off-white solid and poorly soluble in CDC13). it is free

of [1-aC1. The brown. solid sublimation residue is pure [1-HICI. Total yield is 64 96.

[l-HJCI. was charactetized by single crystal X-ray crystallography (appendix 1, Fig. 3 1).

Fig. 31. ORTEP view with hydrogen atoms omitted for clarity. Thermal ellipsoids are at the 50%

probabilîty level. Selected bond distances [pm] and bond angles [O] as follows: C(l)-Cl(I) 328.4(6),

H(lA)-CI(l) 267(5), C(1j-N(1) 1335(7), N ( l j C ( 2 ) 137.7(7), N(2)-C(8) 15 1.7(6), C(3)-C(2)

135.9(7), C(1)-N(IW(2) 108.3(4), C(3)-C(2)-N(l) 107.1(5), N(l)-C(l)-N(2) 108.8(5).

39

2.4.1 Deprotonation of [l-Hl CI to give 1

The irnidazolium salt was deprotonated with "BuLi in THE sublimation gave 72% of

carbene 1 (white powdery, sublimation temp. 60-80 OC).

'BU 'BU I "BuLi THF 1 2S°C I 8 h

b - QU-H (g)

Fig. 32. Synthesis of 1 by deprotonation of (1-Hl CI

Notes:

1. The 1H NMR shifts of the imidazolium salt (in CDCl3) are critically dependent on the

water content of the compound.

2. The 'Bu-cornpound has not been described in the literature, but the 1H NMR data of the

ipr-cornPound has been reported and closely matches that of the Bu compound.

3. Formation of the imidazolium salt is incomplete after 1 h of reflux.

4. 1H NMR of the crude reaction mixture showed two different BU-signals.

5. 1H NMR showed the sublimation residue to be pure imidazolium salt, the sublimate

shows signals at &lH, CDC13, ppm): 1.45 + 1.49 (int. ratio 3: l ) , 1.72, 2.59 ( t ) , 2.77 (d), 4.19 (s, weak), 5.80 (s, weak) and was not further analyzed.

6. The signals of the sublimate are identical to the impurity in the crude material.

7. Attempted deprotonation of 11-Ii] CI with THF I NaH at room temperature did not lead

to the formation of carbene and showed only signals for Il-IQ Cl.

The carbene 1 was further characterized by single crystal X-ray crystallography

(appendix 1, Fig. 33).

Fig, 33. ORTEP view with hydrogen atoms omitted for clarity. Thermal ellipsoids are at the 50%

probability level. Selected bond distances [pm] and bond angles [O] as follows: N(l)-C(I) 136.6(2),

N(l)-C(2) 138.0(2), C(2)-C(3) i34.1(2), N(l)-C(4) 148.9(2), C(1)-N(lbC(2) 112.57(12),

C(3)- C(2)-N(1) 106.23(14), N(2)-C(1)-N(t) 102.19(12).

2.5 Properties of Imidazolium Salts

2.5.1 Basicity of Carbenes and Acidity of Imidazolium Salts

The imidazoliurn sait [l-ZT] Cl is the C-protonated derivative of the stable carbene 1. It

seemed interesting to compare the structures of the carbene with the structure of the carbenium

cation and to establish the relative basicity of different carbenes through proton exchange

reactions. In a preliminary snidy, it was investigated if the imidazolium salt possesses any

significant CH acidity . To this end, mixture of [l-8] Cl and D20 was investigated, but did not

show any H / D exchange products.

Fig. 34. Deuterium exchange reaction of Il-Hl CI

It can therefore be concluded, that the acidity of the imidazolium salt is quite low,

presumably c 20. The [1-Hl Cl salt was first pumped Ln vacuo at oil bath temperature of 180-

190 O C for 18 h to dry the salt. The exchange experiment was perforxned in a flame sealed NMR

tube. No exchange was observed over a period of 7 d at 25 OC and at 1 10 O C for 22 h.

The relative basicity of the carbenes 1 and 2 was studied through a competition experiment.

Fig. 35. Proton exchange reaction behveen Il-Hl Ci and 2

A sealed NMR sample of an equimolar mixture of [bH] Cl and 2 (Fig. 35) in C a 6

showed signals for the conjugate base, narnely the carbene 1. The two carbenes are present in a

ratio of 1 1 2 = 1 1 18. The signals of the carbenium salts were not observed because they are

insoluble in C&j.

For the mixture [2-8] SCN I l (Fig.36), equilibration led to a ratio of 1 1 2 = 7 1 1.

'BU 'BU 'BU 'BU 1 SCN- 1 1 SCN - 1

CbDb [Y. + cN): - N 25 O C ["H N + [)

I 'BU

I 'BU I 'BU I 'BU

12-Hl SCN 1 [l-HI SCN 2

Fig. 36. Proton exchange behveen I2-HI SCN and 1

After 21 d, this ratio changed to 1 I 2 = 2.7 1 1 (Fig. 36). This indicates that the

protonation equilibrium is slow.

Apart from the tBu signals of the newly formed carbeme 2 (1.36 ppm). new signals at

1.67. 1.83, 2.73, and 6.29 ppm which contribute to the formation of [l-H] SCN (1.83, 6.29). It

is noteworthy, that the saturated carbenium salt [2-Hl SCN is insoluble in benzene (absence of

signals in C6&) while the unsaturated salt [l-H] SCN is soluble in benzene (20 gL) . Although the data indicate that the two carbenes are of similar basicity, the obtained data

could also reflect the relative solubilities of the two imidazolium salts. It was therefore

necessary to repeat the investigation in a solvent that dissolves d l 4 compounds without reacting

with them. THF was investigated but found unsuitable because of signal overlap with the b u -

signals and the N-CH2 signals. The 13c NMR of the mixture of 2 and [1-Hl CI (Fig. 35) showed resonance at 16 1.46 ppm which indicates the formation of [ 2 - 9 CI. The signals for Ç(CH3)3

and CH3 were hidden under THE So, a different solvent was desired that would dissolve both

the reactants and the product.

HMPA dissolves [3-R] SCN but does not dissolve [1-A] CI. Although HMPA is very

inert towards reducing agents - many reductions with elemental Li, Na and K can be

conducted in HMPA - oxygen transfer reaction between HMPA and the carbenes 1 and 2 can not be ruled out. The sarne reaction was tried in HMPA, but 11-HJ CI was completely insoluble

in HMPA even though 2 is soluble and stable in HMPA. The reaction mixture only showed

chernical shifts for 2.

43

It was found, that the unsaturated carbene 1 is inert towards HMPA. A mixture of 1 and

HMPA (1: 1) in C& showed only carbene signals at 1.44 and 7.09 ppm. In neat HMPA the

shifts are 1.54 and 7.34 ppm. These values are slightly shifted vs. the values determined in

C@6. The signal of the ring protons is slightly broadened. The reason for this line broadening is

unclear.

A mixture of 1 and [3-H] SCN in HMPA was also measured with a D20 insert and TMS

as intemal reference (Fig. 37). Although the signals for the supposedly formed carbene 3 could

not be unambiguously assigned because they are partially hidden by the strong and broad

HMPA signal at 2.6 ppm. proton exchange must have taken place because the carbene 1 has

been consumed (no signals) and the salt [l-Hl SCN has been fonned (1.76,7.2 and 10.7 pprn).

'BU 'Bu 'Bu 'Bu I ' s o l - 1 1 SCN -

HMPA/DtO CF. + cN): N - 25 OC I I

'BU 'BU I

'Bu l

'BU

13-H] SCN 1 3 [i-Hl SCN

Fig. 37. Proton exchange between 13-HI SCN and 1

Due to it's poor solubility in benzene (10 g L ) , the signals of [3-H] SCN were completely

invisible. The signal at 1.38 pprn is assigned to the new carbene 3, the signal at 4.5 pprn to

HDO. A signal at 1.02 pprn remains unaccounted for.

The 13~(1H) spectrurn of the sample shows the signals for [1-H] SCN (29.49

[C(çH3)3], 60.12 [Ç(CH3h], 121.45 [ÇH=ÇH], 134.66 [ç+-Hl, 160.91 [SÇN-1) and for 3

(29.04,39.42,60.78). The signal for the carbene carbon of 3 was not observed, presumably due

to low intensity.

Although the carbenium salts show variation in solubility, they are al1 non-volatile. Their

ionic composition was verified by X-ray structures (appendix 1). The structures do noi show any

covalent bonding between the carbenium ions and the counter ions CI- and SCN-. In solution,

the NMR shifts of the carbenium salts depends on the nature of the counter ion (Table 4). This is

strong indication for the formation of ion pairs in solution.

11-a CI Il-H] SCN [2=Ef] Cl [SEI] SCN W(CH3)3) 1.8 1 1.84 1.55 1.52

NCcH) 7.7 1 7.4 1 4.05 4.1 1 & C D 0 119.71 1 19.47 57.20 56.86

Table 4. Influence of counter ion and aromaticity on the chemical shifts

A mixture of [LH] Cl and [3-H] SCN was investigated to find out if the contact ion

pairs exchange rapidly on the NMR time scale. At room temperature, there was only one set of

signals for each of the salts. This implies a rapid exchange of the counter ions; in the case of

slow exchange, signal broadening or even four different sets of signals would be expected.

[i- H] Cl [3- H] SCN 11- H] SCN 13- Hl CI

Fig. 38. Proton exchange between 11-m CI and [SHI SCN

The acidity of C- H bonds cm be estimated from the ' J (C,H) coupling constant. The

empirical relation denved from compounds with known hybridizations like ethylene (sp2) is:

IJ (c,H) = 5 * (% S) [in Hz1

Although the equation [69] is strictly valid only for hydrocarbons, it can nevertheless be used to

estimate the relative acidity of other sets of closely related compounds. For the carbenium

cations the following sequence of relative C-H acidities was established (Table 5) .

carbenium 1 J (c,H) 96s p sa1 t [Hz] [l-Hl CI 2 19.7 44 [2-H] cli 201.4 40 [l-Hl SCN 201.3 40 12-H] SCN 199.9 40 13-H] SCN 189.1 3 8

Table 5. % s character in the C-H carbon of the carbenium salts

i obtained by I. Rodezno (unpublished results)

The data are interesting in two respects. First, the effect of ion pairing is clearly visible

from the difference of the coupling constants for the pair [1-H] SCN and [l-H] CI (Av = 8.4

Hz). Second, for [2-H] CI and [2-H] SCN, the coupling constants are very similar (Av = 1.50

Hz). It is also interesting to note that different types of carbenium ion salts can show similar

CH-acidity, e.g., 12-Hl CI / [1-Hl SCN (Av = O. 10 Hz).

2.5.4 Solubilities of Carbenium Salts

The solubility of the carbenium salts in waier and organic solvents was investigated to

properly plan the synthetic work-up and reactions. Table 6 reveals the important influence of the

counter ion.

22 50 20 [SHI SCN 100 1 50 10

Table é. Solubilities of carbenium salts in g/L

46

While the chloride [1-Hl CI is very soluble in chloroform and water, the thiocyanate [l-Hl SCN

is only moderately soluble. A possible explanation is a higher degree of covalency in the

thiocyanate. Solubility data of [2-Hl salts will eventually complete the picture and allow a

consistent interpretation.

2.6 Deprotonation Stntegy to give 2 from [2-H] SCN

The fact that the thiocyanate salts [1-Hl SCN. 12-Hl SCN and [3-Hl SCN can be

obtained from very inexpensive starting materials through hydrodesulfurization makes them

attractive starting materials for the synthesis of stable carbenes.

'BU 'BU

LDA (2.1 cq.) LiSCN 25 OC, THF

I - LDA-H I 'BU 'BU

(2-HI SCN 2

Fig. 39. Deprotonation of 12-HI SCN to give 2

A number of different deprotonation bases were investigated. Diaminocarbenes were

fonned, but, upon attempted sublimation, only decomposition products were isolated. This

cannot be explained with low thermal stability of the carbenes, as al1 carbenes under

investigation were previously obtained by alternative methods (deprotonation of the carbenium

chloride salt, reduction of thioureas) and found to be thermally stable. The characteristic odor of

sulfur compounds noticed in the decomposition products suggests most likely the reaction of

carbene 2 with the counter ion SCN-• This hypothesis suggests a possible modification of work

up to prevent the decomposition reaction. Work up in this thesis consisted of simple transfer of

the crude reaction mixture to the sublimation flask. If decomposition is indeed caused by the

reaction of carbene with the side product LiSCN, the high solubility of the carbene in

hydrocarbons should allow separation of the carbene from the thiocyanate prior to sublimation.

47

The deprotonation base and the nature of the carbenium cation were found to be important.

While [3-Hl SCN gave the conesponding carbene &er sublimation when LDA in THF was

used as deprotonation base, no carbene could be isolated when "BuLi was used as base.

In the case of 12-H] SCN, the carbene could be generated with LDA but decomposes upon

sublimation work up.

Ring opening hydrolysis of the carbenes 2 and 3 was found to be a side reaction during

the isolation of 2 and 3. The 1H NMR of the sublimate at 50 O C showed resonances at 6 ( 1 ~ ,

C&, ppm): 1.32 (int. l), 1.36 (2, int. 1) and 1.55 (int. 3.5) along with resonances for 2-CHO

6(lH, CaDa, ppm): 0.85(s), 1 .Ol(s), 2.7 1(t), 3.34(t), and 8.40(s). Signals of 12-H] SCN were

absent. The signais at 1.32 and 1.55 ppm remain to be identified.

2.7 Deprotonation Strategy to give 3 from [3-H] SCN

The synthesis of 3 from the easily accessible thiocyanate 13-Hl SCN by deprotonation is

particularly important in view of the inaccessibility of the thiourea 3=S (Fig. 40).

'Bu 'BU 'BU I

il C - H -

THF NH I

'Bu

[SHI SCN 3 3-CHO

i ) 2. t equiv. of "BuLi or LDA or Cdimethylamino-pyridine

Fig. 40. Deprotonation of [%Hl SCN to give 3

The sublimation gave the following fractions (Table 7).

Sublimation Weigbt Appearanee

90 - 100 0.04 black grandar residue 0.5 1 black solid

Table 7. Sublimation hctîons for the deprotonation of P-m SCN wiîh LDA

48

The coiorless liquid (80-90 OC, Table 7) was identified by 1H NMR to be 3 (6(1H): 1.38,

1.67,2.67 ppm) (Fig. 41).

n t -

Fig. 41. I H NMR in CgDg of the 80-90 OC fiaction (colorless oil)

The sublimation residue contained a rninor product with signais at 0.85 and 1.03

ppm. This product is tentatively identified as the ring opened hydrolysis product 3-CHO. This

interpretation is also supported by the isolation and structurai characterization of the analogous

2-CHO.

Fig. 42. Stnicture of 3-CHO

2.8 Other Deprotonation Bases

4-Dimethylamino pyridine as possible deprotonation base was tested for both [2-H]

SCN and 13-H] SCN but did not react (r. t., 4 h, 1H NMR). The use of "BuLi was also

unsuccessful in the deprotonation of [2-tn SCN and [3-EI] SCN. This is in line with the known

nactivity of the thiocyanate ion (Fig. 43).

Fig. 43 Reaction of SCN' with "BuLi

DMF Chloride

'BP Mtthod 1 rNH DMF Chloride

Fig. 44. Reaction schemes for 13-HI CI formation

'9 ,& Mtthod 2 *O C h

PbCI2 or HCI N te:

A solution to this problem would be the use of chloride salts instead of thiocyanate salts.

Two methods for the synthesis of chloride salts are curiently being investigated (Fig. 44).

50

f 9 Aromatic, Anü-Ammatic d Linear Coqjugated Poly-carbenes

The strong aromatic delocalization in the diaminocarbene 1 suggests that polycarbenes

of the general type (R-N-C:), should also be delocalized.

Fig. 45. Delocalized poly-carbenes

Calculations (M. Denk, unpublished results) indicated, that the aromatic carbene 7 (Fig.

45) is perfectly planar (MP2 / 6-3lG*) (LNCN = 108.20, LCNC = 13 1.80) while the anti-

aromatic carbene 6 adopts an envelope geometry (LNCN = 87.g0, LCNC = 85.30). The C-N

bond distances in 7 were found to be equal and short (137.6 pm). The anti-aromatic carbene 6

shows elongated C-N bond distance ( 14 1.3 pm).

None of the representatives in Fig. 45 excluding 1 has been obtained. Especially, the

aromatically stabilized tris-carbene 7 was considered to be a candidate of potential high

stability. Possible strategies for the synthesis of 7 are oudined in Fig. 46. Investigations in this

thesis are restricted to the synthesis from the possible desulfurization of tris thiourea 11. The

desulfurization method had been previously developed in Our group and is well suited for the

synthesis of both stable and transient diaminocarbenes [7]. The trimerkation of isonitriles is

endothermic (MP2 / 6-3 1 G* level).

5 1

The synthesis of the tris thiouna 1lfBu proved to be a formidable task. While the îris-

methyl derivative Il-Me cm be obtained via a traditionai multistep synthesis. al1 other membea

have k e n obtained from ultra high pressure trimerizations [42].

w

dchydrogcnation

\ k//" F/ F

RA *\R fi' S

11 only known for R = Me, Et, "Pr, "Bu, Ph

Fig. 46. Synthetic strategies for tris-carbene

The group of Yoichi Taguchi in Japan succeeded in trimerizhg Me isothiocyanate (12-Me) to

1,3,5-trimethyl- l,3,5-triazine-2,4,6 (lH,3H,SH)-tnthione (Il-Me) (Fig. 47) under high pressure

(800 MPa) [42]. The reaction also requires catalysis by Et3N: or pyridine. Sterically hindered

pyridines do not catalyze the reaction.

Fig. 47. Synthesis of 1bMe

52

The rate of trimerization of 12-Me was found to be proportional to the amount of

triethylarnine catalyst used. Ethyl isothiocyanate also trimerized in high yield under the same

reaction conditions. Bulkier groups like R = "Pr, "Bu, allyl, Ph, and cyclohexyl gave very low

yields. A second protocol using DBU as catalyst under 800 MPa at 130 O C for 20 h resulted in

the trimerization of "Pr and "Bu isothiocyanates in good yields but failed for larger alkyl groups

( i ~ r , tBu). Allyl isothiocyanate polymerized in the presence of DBU but the trimer was obtained

in the presence of triethylamine at even higher pressures ( 1200 MPa) in good yield (421.

This serves to illustrate that general methodologies for the synthesis of tris-thione-

triazines 11 remain yet to be developed.

Attempts by Martin Ma in Our group to develop catalysts for the low pressure

trimerization of 12 to give 11 were unsuccesful. It was therefore decided to investigate the

transformation of 9 -> 11 by dehydrosulfurization. The transformations 9 -> 7 and 10 -> 7 are

cumntly under investigation in our laboratory. The transformation of aminals into carbenium

cations is demonstrated in this work for 1-Hz, 2-Hz and 3-H2.

2.10 Reactivity of lJJ- tri-tefi-butyl-hexahydro-sym-triazine with Sg

The reaction of 1,3,5-tri-tert-butyl-hexahydro-sym-Win with eIemental sulfur ai 140 -

160 OC gave mixtures that were separateci by sublimation (Fig. 48). The degradation products 13

and 14 that form the volatile part are readily explained. No mechanistic explanation can be

offered for the formation of [1-HJ SCN (17% yield, sublimation residue). Although surprising

and unexplained, the formation of [l-H] SCN (17 %) constitutes an inexpensive and fast

synthesis for this compound.

Sublimation weight Appearance Assignment Temp. [% yield]

--80 35 crystalline, yellow 14 80 - 120 36 crystalline, yellow 13 120 - 140 - oily, orange 13114= 1.5/1 residue 17 flaky, oranp;e [l-a] SCN

Table 8. Dehydrosul~t ion of 1,3,S-tri-tert-butyl-hexahydr0csym-triaPne (140 OC, 26 h),

53

The absence of Il-'Bu was confirmed by NMR (IH, ' 3 ~ ) and GCIMS. Upon dissolving

the sublimation residue in CHC13 and layering with twice the volume of hexanes, a brown

precipitate was obtained.

'BU SCN - I [EH + I

'Bu

Il-HI SCN

314 S*

'BU

yN4 , N ~ N \

'BU S 'Bu

Fig. 48 Decomposition products of the reaction of 9 with Sg

This presumably polymeric material is insoluble in water and displays a characteristic

NH band (3643 cm-'), and a strong and broad band at 2061 cm-1 (-N=C=S), and an N-C=C

band (1651 cm-').

While the formation of 13-Di-teri-butyl thiourea 13 is supported by NMR (IH, 1 3 ~ ) and

GC/MS, evidence for the formation of tert-butyl thiourea 14 is less convincing (lH, 1 3 ~ NMR).

Table 8 illustrates the fractions obtained by a typical work-up.

The CHCl3-soluble part of the sublimation residue is pure [l-Hl SCN and was

characterized by single crystal X-ray crystallography (Fig. 49).

Fig. 49. ORTEP view with hydrogen atoms omitted for clarity. Thermal ellipsoids are at the 50%

probability b e l . Selected bond distances [pm] and bond angles [O] as follows: S( 1 )-C( 12) 164.94( 18).

Repeating the reaction led to the product distribution outlined in Table 9.

sublimation temp. weight ~ppearance - ~orn~chents-. r Oc1 Egramsl

6 0 - 100 1.55 oily, yellow 2 + 14 100 - 140 140 - 180 180 - 195 195 - 200 200 - 220 residue

1 .O0 flaky, yellow 2 O. 12 creamy, yellow 2 0.47 creamy, yellow 2 0.26 oily, yellow [BUNCS + 15 0.63 crearny, pale yellow 2 + 14 0.5 flaky, pale yellow 1 + ~BUNCS +

15

Table 9. Sublimation fiactions obtained fiom large scale dehydrosulfuritation o f 1,3,5-tri-tert- butyl-hexahydro-sym-criaine at 150 OC, 58 h

None of these fractions contained Il-tBu and the residue was not [1-H] SCN (lH, 1 3 ~ ,

GC/MS). A possible reaction scherne for the formation of the tris-thiourea would be as follows

(Fig. SOa,b) .

'BU, 4 'Bu HN N'

Fig. SOa. Reaction scheme for the dehydrosulfurization of 1,3,5-tri-tert-butyi-hexahy&o-sym-triazine

Fig. SOb. Possible sulk-exchange reaction between 9 and 15

56

A 13C NMR simulation software was used to simulate t h e I 3 ~ NMR shifts for mono-,

bis- or tri-substituted thioureas (Fig. SOC).

Fig. SOC. I3c NMR simulation of mono-, bis-, tri- substinited thiourea

2.10.1 Multistep Approaches for the Synthesis of Il-'Bu

Compound 16 is a necessary intermediate in the synthesis of Il-

57

This may be due to the superposition of the signals of 16 and another unidentified product. The

formation of the triazine 9 c m be ruled out on the basis of its 1H NMR data (1.05, 3.45 ppm).

The 13-Di-tert-butyl thiourea used in the reaction was contarninated with 28% mono-tert-butyl

thiourea (IH NMR). This presumably led to a mixture of products upon reacting it with

paraformaldehyde and tert-butyl amine.

The 13C(lH} spctmm of the crude in CDCl3 showed strong signals at 29.41 and 29.87

ppm, with weak signals at 30.97, 122.63, 128.5, 134.25 and 224 ppm. No signal around 180

pprn was observed and also no signals for quarternary carbon around 50 ppm were observed.

From the FT-IR data (NaCl, nujol), bands at 3301 and 3266 cm-' appear as a doublet indicating

an NH2 stretch.

Al1 these results support the absence of the mono-substituted thiourea and the presence

of a mixture of 13 and 14 (1H NMR).

2.11 1,3,5-tri-tert-butyl-hexahydro-sym-triazine and conformations in other 1,3,5-triazines

As discussed in chapter 2.9, 1,3,5-tri-tert-butyl-hexahydro-sym-triazine 9 is a potential

starting material for the synthesis of the tris-carbene 7. Like most hexahydro-sym-triazines, 9 is

in equilibrium with the imine CHZ=N(~BU) 4. This chapter will discuss the synthesis and

properties of 9 and its derivatives.

1,3,5-triazacyclohexane, the most simple of hexahydro-triazines was obtained in 1895

from a mixture of aqueous formaldehyde-ammonium chloride upon addition of potassium

carbonate but has never been obtained as such [42]. Obviously, this compound transforms into

the very stable urotropin with it's tetra-aza-adamantane structure. In solution, the compound is in

equilibrium with irnine CH2=NH. Hexahydro-synt-triazines with substituents on nitrogen can

not form urotropin and are typically more stable, but can also dissociate into imines.

Hexahydro-sym-triazines can exist in different conformations as Table IO shows

structurally c harac terized exarnples (Cambridge Database up to May 1 998).

58

As the data show, the equatonal, axial, axial (eaa) conformation is the most common,

eea and even aaa conformations are known.

Ri = R2 = R3 Conformation Ref. aaa 57 eaa eaa eea eee eee eea eea eea eaa eaa eaa

PhOCH7- eaa 66

Table 10. Conformations of hexahydro- l,3,5-triazines (hexahydro-sym-uiazines)

Reaction of 'Bu-NH2 with parafomaldehyde gives 1,3,5-tri-tert-butyl-hexahydro-sym-

triazine after one day of reaction at r. t. The use of paraformaldehyde is convenient because its

dissolution allows to monitor the reaction [S. Rodezno, unpublished results]. The triazines

separate from aqueous solution as oily layers that c m be separated and drkd with Ba0 or KOH.

For MeNH2, no phase separation was observed and the product was isolated by repeated

extraction with Et20.

Reaction time is only 20 mins. in this case. 33% solutions of fonnaidehyde react even

faster but lead io products of lower punty.

ta..

Fig. 52. Synthesis of 1,3,5-tri-tert-butyl-hexahydro-sym-tnazine

As generally found for hexahydro-sym-triazines, compound 9 is in equilibrium with 4.

The formation of 9 is favored in concentrated solutions.

59

This equilibrium leads to the pualing observation, that in C&, the ratio of 9 1 4 is

concentration dependent. As expected, dilution leads to a decrease of 9 1 4. In the more polar

CDC13, sipals for 9 are weak or even absent, while the polar imine 4 is obviously stabilized by

polar solvents.

Attempts to obtain crystds for the triazine 9 failed and gave only sticky oils. This could

be due to the fact that 9 is a mixture of different anomers. However, a melting curve recorded

for 9 gave only one small inflection point at 5 OC (Fig. 53).

Melting point of 1,3,5-tri-tee-butyl hexa hydro-s- triazine

Fig. 53. Graphical representation of the meiting point of 9

60

2.12 Dehydrosulfurization of Urotropin

Urotropin is nlated to the hexahydro-s-triazines studied in this thesis. Attempts to obtain

dehydrosulfunzation products with cage structure led to the formation of methylurotropiniurn

thiocyanate [S-CH31 SCN as the only identifiable product (Fig. 54). The compound was

characterized by single crystal X-ray crystallography (Fig. 55).

5 [S-CH3] SCN

Fig. 54. Synthesis of methylurotropiniurn thiocyanate

+ unidentified cornpounds

Fig. 55. ORTEP view with hydrogen atoms omined for clruity. Thermal ellipsoids are at the 50%

probability level. Selected bond distances [pm] and bond angles [O] as follows: N(4)-C(6) 116.2(3),

S(I>-C(6) 165.2(2), N(2)-C(2)#1 153.12(17), N(2+C(5) 148.0(3), C(3)#1-N(3) 147.59(17),

C(SbN(2>-C(2) 1 1 l.l4( IO), C(2+N(2+C(l) lO8.l7(lO), C(2*1-N(2)-C(l) 108.17(10), N(1+

C(2+N(2) 1 10.18( 121, N(l)-C(3&N(3) 1 1 1.78(12), N(lH(4)-N(1)#1 1 1 1.80(16), N(4)-C(6)-

S(1) 179.7(2).

61

The fluoride analog of the salt has been introduced recently as a source of naked fluoride

ions by Clarke et al. Methylurotropinium fluoride dihydrate can be obtained from urotropin and

methyl iodide via 1-meihylhexamethylenetetraarnine iodide, which is then converted to the

corresponding fluoride by metathesis with AgF. The compound has high thermal stability and

the large size of the cation makes it a g w d source of F- ions. More recently, Robert Gnann and

coworkers have reported a single-step one pot synthesis of this compound and it's application in

the isolation of the anhydrous fluoride as well as in a coupling reaction [43].

2.13 Reaction of Carbones and Carbene Analogs with Alkoxides

The oxidative addition of metal salts MX with X = RO, Hal, NR2 etc. leads to

carbenoids. Carbenoids are typically obtained by lithium-halogen exchange from 1, l-dihalo-

alkane. They only possess marginal stability and decompose above -100 O C to give the typicai

decomposition products of free carbenes [44].

Fig. 56. Decomposition of halogen substituted carbene species to carbenoid

The reductive elimination of alcohols from ester-arninals N2CH-OR to give carbenes

N2C: has been applied for the synthesis of tetraamino-olefins from amines and ortho-esters (Fig.

57).

Fig. 57. Reductive elirnination of alcohols

62

There is, however, no evidence for the operation of this mechanism other than the formation of

the enetetraamine. Even the thermodynamic equilibrium between N2CH-OR / N2C: + ROH is unclear at present. Silylenoids, the sila-analogs of carbenoids have received little attention but

are now investigated by the group of K. Tamao at Kyoto [44]. The possible oxidative addition

of alcohols to carbenes 1 and 2, L'Si: and LGe: was investigated to this end.

The oxidative addition of tBuOCu, 'BuOLi, tBuOH and MeOH to the carbenes 1 and 2

as well as their sila- and germa-analogs was investigated. The [BuOLi in this study was obtained

from BuOH (as received) and nBuLi.

The [BuOCu has the unique property of strong affinity towards n-accepting ligands [93,

941 and was obtained from tBuOLi and CUI and purified by sublimation ( 130 - 150 OC, 0.1

Torr).

The reaction of tBuOH with carbenes 1 and 2, L'Si: and LGe: was investigated. To

study the effect of steric hindrance, BuOH was replaced with MeOH.

2.13.1 Reactions of Carbenes with Alkoxides and Alcohols

Carbenes 1 and 2 did not react with tBuOCu both at r. t. and after prolonged heating at

110 OC for 7-10 d. The reaction of carbene 2 with tBuOLi showed absence of starting materiai

and the presence of new signals at 1.32 (2H), 1.35 (1 H) and 3.05 ppm (0.5H) that suggested the

formation of 2-(0t~u)~i

dilute sample.

1 'BUOL~ - THF

(Fig. 58). A 1 3 ~ NMR of this sample could not be obtained due to a

' ~ p

[NU"" + I

'Bu

Fig. 58. Synthesis of 2-(0fBu)~i

63

Attempts to repeat the reaction only led to the formation of the hydrolysis product 2-

CHO that was charactenzed by single crystal X-ray crystallography. No reaction occurred

between tBuOLi and 1 (25 OC 1 7 d followed by 100 O C 1 14 d) (Fig. 59).

'BU 'BU I I

1 'BUOL~ N O 'BU

N Li I

'BU I

'Bu

Fig. 59. Reaction of I with 'BuOLi

Reactions of tBuOH with 1 and 2 only gave hydrolysis reaction and were not pursued

any further (Fig. 60).

Fig. 60. Reactions of I,2 and LGe: with 'BUOH (1:2)

No reaction was observed between 1 and MeOH even after heating over a penod of 7 d

ai 100 O C . Reaction of 2 with MeOH showed signals for 2-(0Me)H at &'H, C&, ppm): 1.13,

2.73, 2.94, 3.24, 5.23 and a minor product: 6(lH, C6D6, ppm): 0.86, 1.01, 2.57, 8.40 identified

as 2-CHO upon sublimation work up (Fig. 61).

'BU 1 McOH 'BU I 'Bu

I 25 OC

Mat

I NH

'BU I

'BU I

'Bu

2 240Me)H 2-CHO

Fig. 61. Synthesis of 24OMe)H using I : 1 ratio of 2 to MeOH

Compound 2-CHO was characterized by single crystal X-ray crystallography (Fig. 62).

Fig. 62. ORTEP view with hydrogen atoms ornitted for clarity. Thermai ellipsoiâs are at the 50%

probability level. Selected bond distances [pm] and bond angles [O] as iollows: N( l ) -C( l ) 134.14(18),

N(l s ( 2 ) l49.38( 18). C( 1 ) -C(6) 152.5(2), C(6)-N(2) 145.86(18), O(I)-C(11 j N ( 1 ) l23.98(14),

C(t)-N(lH(2) 1 l8.7O(ll), N( l ) -C( l jC(6) II4.15(12).

2.13.2 Reactions of L'Si: with Alkoxides and Alcohob

The reaction of L'Si: with tBuOCu gave new product signals at &lH, C6D6): 1.28

(18H), 1.32 (9.8H), and a broad doublet at 5.80 (PH) after heating (LOO OC, 10 d) dong with a

color change of the solution from orange to dark brown and a black film on the upper parts of

the NMR tube. This indicates the formation of copper requiring the oxidation of L'Si: (1H and

13C NMR) (Fig. 63).

L'SI: L~S~-(O~BU)CU

Fig. 63. Attempted synthesis o f L's~-(O

66

Attempts to obtain compounds of type L'Si(0R)Cl or L'Si(0R)z from the silane L'Sic12

did not succeed. Reaction of L'Sic12 with tBuOLi (1:l) at 25 O C or at refluxing temperature

produced a color change but no new products (Fig. 65). Use of BuOH + pyridine instead of BuOLi also did not give substitution products.

8 THF

N CI I

- LiCl 'BU

I 'BU

L'Sic12 L'S~-(O~BU)CI

Fig. 65. Attempted synthesis of L' s ~ - ( O ~ ) C I

tBuOH readily adds to the silylene L'Si:. The product was isolated by sublimation of the

crude mixture 45 O C - 80 O C (oil bath, 0.1 Torr) as off-white crystals (56% yield) and

characterized as L'Si-(0tBu)H (IH, 13C NMR) (Fig. 66).

'BU 'BU l I

2 'BUOH

N THF H I

'BU I

'BU

L'Si: L's~- (0%)~

Fig. 66. Attempted synthesis of L~s~-(oBu)H

Surprisingly, no reaction of L'Si: was observed with MeOH.

2.13.3 Reactions of LGe: with Alkoxides and Alcohols

No reaction was observed between LGe: and tBuOCu or tBuOLi (Fig. 67).

LGe: LG~-(O'BU)L~

Fig. 67. Attempted synthesis of LG~-(O~BU)L~

Reaction of LGe: with 'BUOH (Fig. 60) or MeOH only led to the formation of 2-C and

the starting material LGe: ('H NMR). Table 11 summarizes the outcome of the reactions of

carbenes 1 and 2, L'Si: and LGe: with alkoxides and alcohols.

t ~ u ~ ~ u t ~ u ~ ~ i t ~ u ~ ~ MeOH

1 - - - - 2 - + + +

L'Si: + + + - LGe: - - + +

Table 11. Surnmary of reactions of 1,2, L'Si:, LGe: with alkoxides and alcohols

+ indicates reaction, - indicates no reaction

2.14 Synthesis of 1-Hz

The carbenes prepared in this thesis were investigated by core electron spectroscopy in

the group of A. Hitchcock at McMaster University.

Photo electron spectroscopy is a method that allows to determine the binding energies of

electrons in individual occupied orbitals. Core electron spectroscopy [45], on the other hand,

allows to map unoccupied orbitals. This method involves the excitation of core electrons into

the unoccupied bonding or anti-bonding orbitals.

68

The energy and the intensity of the transition, for instance, allow to determine whether a

x* orbital is localized or delocalized.

For the purpose of cornparison of spectml data, the synthesis of 1-H2.was atternpted.

Reaction of [1-H] CI with BH3-THF, LiAIH4 or catalytic hydrogenation of 1 (H2 / Pd) was

studied. The reaction of [l-HI Cl with BH3 gave a broad product spectrum and was not

investigated further. With LiAIH4, 1-H2 was obtained but decomposed whenever attempts were

made to isolate the compound (Fig. 68).

118 LiAlH, THF 'BU I

abH 25 OC 5 min N - LiCI

- [*yH I

N H

'BU I

'BU

(1-HI CI

Fig. 68. Synthesis of 1-Hq

In solution, 1-H2 is stable indefinitely (fiame-seded NMR tube) but decomposes rapidly

upon exposure to minimal traces of air or moisture. Thus, al1 attempts to isolate the compound

in pure form only led to greyish solids that are presumed to be polymeric bH2. The instability

of l w H 2 is surprising in view of the fact that a number of derivatives e. g. [1-a+, 1=0 and l=S

are thermaily robust and can be isolated by sublimation without difficulties. It is likely that the

N-CH=CH-N fragment is stable only in conjugation with -M substituents such as C=O, C=S

etc. The sila analog L'SiH2 is also very air-sensitive but can be isolated by distillation (M.

Denk, personal communication).

69

2.15 Reaction of 1 with Fe(C0)s

The stable silylene, L'Si:, readily reacts with metal carbonyls to give silylene complexes

(L'Si)2Ni(C0)2 [46], L'Si=Fe(CO)q (unpublished results) and other L'Si-metal complexes.

To establish the relative reactivity of stable silylenes and stable carbenes, the reaction of

1 with Fe(C0)S was investigated.

With electron-rich carbene ligands, thermal disproportionation has been found to yield

biscarbene complexes (Fig. 69) [47,48] .

M = Cr, Mo, W

Fig. 69. Synthesis of a bis-carbene complex

The reaction of 1 with Fe(CO)5 (1:2) resulted in the formation of a yellow, powdery

solid that was isolated by sublimation at 70 O C in vacuo in low yields and starting material 1

that sublimed at 60 OC in vacuo. The CO stretching frequencies (V = 2024, 19 12, 1898 cm- l ) of

the yellow sublimate at 70 OC indicate the presence of terminal carbonyl groups. The

sublimation residue (brown solid) did not show CO bands.

1 1 ~ F e ( c 0 ) ~

Fig. 11. Attempted synthesis of l=Fe(COh

70

Based on the unusually high volatility (80 OC I 0.1 Torr), the q S carbene complex

1=Fe(C0)2 is more likely than the ql complex (Fig. 70). This is supported by the IR specinim

mat shows two strong bands (v(C0): 1898 (asym.), 1912 (sym.) cm-').

'BU ?

1 1 =Fe(CO)4

Fig. 70. q l complex formation: l=Fe(CO)4

Attempts to crystallize the yellow sublimate failed both by layering a 1 :2 solution of

THF and hexanes and by heating it in a flame-sealed NMR tube to 1 10 OC (oven) over a period

of 7 to 14 d. The sublimate transformed into a brown tarry material upon heating. Due to it's

poor solubility in C&, NMR was measured in THF with a drop of TMS and a D20 insert as a

lock solvent. The shifts for rert-butyl carbon and the quaternary carbon were overlapped by

strong THF signais (26.38 ppm, 68.22 ppm). Signals at 129.01 ppm (N

71

After heating at 110 OC for 16 h. dong with signals for 2 and 2-CHO, new signals at

1.17+ 1.5 1 (int. ratio 9 : l), 5.25+6.80+7.74 (int. ratio 2 : 1 : 1) developed. No change was seen

in the spectmm after continuing to heat for 7 d. The appearance of new signals indicated a

reac tion .

Fig. 71. Aaempted synthesis of 2=Fe(CO)4

When repeated on a larger scale (0.14 g 2 + 0.30 g Fe(C0)5), different results were different. The FT-IR data of the crude mixture suggested the presence of an Fe(C0)2 fragment

with two strong CO bands at v = 1848 cm-' and 1908 cm-'. Sublimation gave two fractions: 45-

50 OC, colorless crystalline, 40 mg and 60-70 OC, purple, crystalline, 9 mg. Both the volatile

fractions were characterized as 2-CHO by IR specuoscopy. The sublimation residue (33 mg,

brown powder) showed CO frequencies at 1842 cm-1 and 19 15 cm-'.

2.17 Aromatie Delocalization in Stable Carbenes: Correlation of Experimental and

Cornputationd data

2.17.1 Introduction

The relative extent of aromatic delocalization in stable diaminocarbenes (1,3-

imidazolylidenes, 1) and the related species 1=0, l=S and 11-Hl+ was studied at the B3LYP /

6-3 lG* level. The criteria used to evaluate the relative extent of aromatic delocalization were:

HOMO-LUMO gaps (Eg), bond order (Mulliken and Lowdin), C=C stretching frequencies and

experimental NMFt data (1H and 1 3 ~ NMR).

72

For the derivatives of the carbenes, the C=C stretching frequencies, the HOMO-LUMO

gap energies and the bond orden lead to different sequences of increasing delocalization.

corn pou nd l-HZ 110 [I-HI+ 1 6 1 L' B' LW+

V [ C ~ [cm- J 1 706 1 649 164 1 1638 1630 1626 1591

Table 12. Increasing delocalization as obtained fiom complrtational IR fiequencies

compound 1-Hz 1 4 1 L'B' 1 1 - ~ + LIN+

Bond Order 1.86 1.77 1.72 1 .71 1.68 1 .58

Table 13. Correlation between bond order and NMR data

- - -

corn pou nd L'Ba 1 4 [~-HI+ f L'N+ ~ -HZ

Eg! [eV] 82.00 235.86 248.12 248.2 1 248.87 1591.4

Table 14. Conelation between Eg and aromatic stability

The only criterion that directly correlates with experimental data is the Lowdin bond

The recent synthesis of stable, diaminocarbenes 1 [6] and the isostructural stable

silylenes [49], germylenes [SOI and phosphenium cations [5 1, 521 has triggered an ongoing

debate about the extent of aromatic delocalization in these species. While there is liale doubt

that heterocycles 1 are aromatically stabilized to some extent or the other, the extent of

delocalization, that is the relative importance of the mesomeric structure l b us. la , is unclear

(Fig. 4).

R R R I I 1

[*.: R = adamantyl c): - @: mesityl I

metbyl I R R

I R ~ - P ~ O P Y ~

ter& buty l

Fig. 4. Aromatic divalent carbenes la and 1 b and non-ammatic carbene 2

73

The controversy is essentially caused by the need to reconcile computational data

with experimental data that are obtained from such different approaches as single crystal X-

ray crystallography, NMR, neutron diffraction and the measurement of optical and magnetic

properties.

Surprisingly, little attention has k e n paid to the investigation of delocalization

through computationally derived bond orders in species 1. Bond orders can only be obtained

by calculations but they can correlate with vibrational data. E. g. the stretching frequency of

the C=C double bond in heterocycles 1 should correspond to the bond order and should

decrease with increasing delocalization (Fig. 4).

Examination of experimental IR data for the compounds L'E: (E = C, Si, Ge) in our

group has shown that the CC-stretching frequencies are weak and easily obscured by other

strong bands (VCN, VW). The CC-stretching bands are however easily measured by Raman

spectroscopy and are in fact the strongest bands in the region 2500 - 800 cm-'. Some disadvantages of the experimental approach remain. Only a srnall number of

possible compounds of type 1 have been characterized and the precise location of vcc band

can become obscured by Davidov splitting or symmetry enforced splitting resulting from the

syrnmetry of the solid (space group).

An obvious alternative would be the accurate calculation of vcc. The calculation of

accurate vibratory spectral data from fint principles is still a formidable task. Without going

into the details of the problem, the difficulties are arnply illustrated by an inspection of the

contemporary arsenal of computational methods. Among the overwhelming number of

different semi-empirical methods: ab initio methods, density hinctional methods and hybrid

density functional methods, only one approach, the B3LYP hybrid method, has consistently

delivered accurate vibrational frequencies [8,56].

The accuracy of B3LYP 1 6-31G* calculations is typically better than 2 W. Even

better agreement between experiment and theory can be achieved by the introduction of

scaling factors. These factors depend on the type of bond investigated and can be optimized

by a least squares fit of experimental and computational values [8].

74

In the context of this study, the goal is not to maximize agreement between

experimental and computational values (vibratory data), but, rather to study trends in the

delocalization for the family of heterocycles 1 and 2 with divalent fragments, E.

'Bu I ci-

& N I

'BU

'Bu I

N

I (1-HI Cl 1-Hz 1- l=S

Fig. 72. The stable carbene 1 and its derivatives

B3LYP / 6-31G* calculations are more time consuming than HF / 6-31G*

calculations. Even for R = H, the calculation of the heterocycles 1 and 2 requires 30 - 40 h of CPU time on a Silicon Graphics Workstation with a R4400 processor and 128 MB of RAM.

The calculations are useful beyond the goal of obtaining vcc data. Like other DFi'

methods, the B3LYP method automatically includes electron correlation. While the effect of

electron correlation on the structural accuracy is not always clear [ I l ] , electron correlation

can be essential to obtain accurate thermochemical data like heats of formation etc. The

B3LYP 1 6-31G*