Oxygen-sulfur rearrangement in the reaction of thiocarbamate imidazolium ylide with arylaldehyde

Article abstract of DOI:10.1039/c2ob26520f

The nucleophilic addition of thiocarbamate imidazolium ylide to aldehyde triggered sequential intramolecular N to O migration of thiocarbonyl amide group and reversible oxygen-sulfur rearrangement to afford 2-imidazolium alkylcarbamothioate. The ortho gro

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Oxygen–sulfur rearrangement in the reaction of thiocarbamate imidazolium
ylide with arylaldehyde†
Yingwei Zhao, Min Lei, Lei Yang, Feng Han, Zhen Li and Chungu Xia*
Received 2nd August 2012, Accepted 12th September 2012
DOI: 10.1039/c2ob26520f
The nucleophilic addition of thiocarbamate imidazolium
ylide to aldehyde triggered sequential intramolecular N to O
migration of thiocarbonyl amide group and reversible
oxygen–sulfur rearrangement to afford 2-imidazolium alkyl-
carbamothioate. The ortho group on phenyl of aldehyde
strongly affects the balance of the O- to S-rearrangement.
The rearrangement of O-aryl or O-alkyl thiocarbamates into their
corresponding S-isomers is a practical way for the preparation of
Scheme 1 Preparation of N-thiocarbamate imidazolium salt 1.
thiophenols or thiols from phenols or alcohols. Among many
reactions belonging to this group, the OAr to SAr migration in
aryl thiocarbamates which is commonly referred to as the
Previous literature showed that an N-aroyl imidazolium ylide13
or N-carbamate imidazolium ylide14 can be generated in situ by
Newman–Kwart Rearrangement (NKR) has been extensively
studied.1 Due to the importance of alkyl thiocarbamates2 in its
treating the corresponding imidazolium salts with base, which
applications in medicine3 and pesticide syntheses,4 the chemistry
subsequently can be trapped by electrophiles to afford 2-substi-
of intermolecular or intramolecular rearrangement of O-alkyl
thiocarbamates has also been an important research topic.5
However, achieving these transformations often requires harsh
thermal conditions,6 special catalysts,7 photochemical acti-
vation,8 or existence of special groups on the substrate structure.9
In conjunction with the project on the study of functionalized
imidazolium salts ongoing in our laboratory, some of which
were known as ionic liquids,10 we were interested in discovering
whether some special chemical properties could be exhibited
when thiocarbonyl was introduced to their molecular structure as
a functional group, and the chemistry of N-thiocarbonyl imidazo-
lium salts was the focus of our study. To the best of our knowl-
edge, no prior reports of these compounds could be found in the
literature and only a few mentioned that thiocarbonyl imidazo-
lide was used as a protective group for alcohols.11
tuted imidazoles, although the reactions for N-aroyl imidazolium
ylide are not easy to control and for N-carbamate imidazolium
ylide, a carbamate group of small size is needed.
We assumed that salt 1 would be deprotonated in the presence
of an amine base to form N-thiocarbamate imidazolium ylide
which could be trapped by electrophile benzaldehyde (2a), pro-
ducing 2-substituted-1-benzylimidazole. The initial experiment
of this project was carried out in DMF at room temperature.
After the reaction, the only product was isolated and
recrystallized.
X-ray diffraction analysis15 revealed that its structure (3a) con-
tains a carbonyl group instead of a thiocarbonyl group, indicating
that oxygen–sulfur interchange has occurred at some stage
during the process (Scheme 2).
Scheme 3 shows the presumed reaction process which
includes deprotonation of imidazolium salt 1 to generate the
N-thiocarbamate imidazolium ylide, nucleophilic addition to
benzaldehyde to afford a zwitterionic intermediate, intramolecu-
lar nucleophilic attack on the thiocarbonyl to form O-(imidazolium)-
(phenyl) methyl thiocarbamate, and the final oxygen–sulfur
rearrangement.
Firstly, 1-methylimidazole was allowed to react with
dimethylthiocarbamate chloride to prepare N-thiocarbamate imi-
dazolium salt 1 as light yellow crystals (Scheme 1). It is known
that imidazolium salts easily lose a proton at the 2-position.12
State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou, China. E-mail: cgxia@licp.cas.cn; Fax: +86-931-4968129
†Electronic supplementary information (ESI) available: Experimental
detail for the reaction of imidazolium salt with arylaldehydes; character-
To study the influence of conditions on this new reaction,
initially, the model reaction was carried out in different solvents
(Table 1). We found that the transformation was accelerated in
polar aprotic solvents. In the presence of Et3N and using DMF
as solvent, an isolated yield of 95% was obtained (entry 3).
DMSO and acetonitrile also appeared to be good solvents
(entries 1 and 2), but the protic solvent methanol was not
1
ization data including H NMR spectra, 13C NMR spectra, HRMS, and
X-ray crystallographic data. CCDC 880883. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI:
10.1039/c2ob26520f
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Scheme 4 Reaction of thiocarbamate imidazolium ylide 1 with 2,6-
dichlorobenzaldehyde 2b.
Although the widely used Et3N was successful for deprotona-
tion of the imidazolium salt 1 to form carbamothioate, various
other bases were also tested. High yields of product were also
achieved when using strong inorganic bases such as Cs2CO3 and
NaOH (Table 1, entries 7 and 8). However, in the presence of a
weak base such as KOAc, the reaction proceeded extremely
slowly (Table 1, entry 9) and the use of pyridine led to nearly no
product (Table 1, entry 11).
Scheme 2 Reaction of N-thiocarbamate imidazolium salt 1 with ben-
zaldehyde 2a and the ORTEP illustration for the product 3a (hydrogen
atoms were omitted for clarity).
To further extend the scope of this protocol, the thiocarbamate
imidazolium ylide was allowed to react with other substituted
arylaldehydes. To our surprise, treatment of 2,6-dichlorobenz-
aldehyde 2b with the imidazolium salt 1 at room temperature gave
the corresponding O-alkyl thiocarbamate 4b16 in quantitative
yield instead of the rearranged product carbamothioate 3b
(Scheme 4). This means the O–S exchange had not happened for
this substrate at the standard reaction conditions.
Based on this interesting finding, we then decided to subject a
wide range of arylaldehydes to these reaction conditions to study
the substituent effect in detail. The reactions were carried out
under standard conditions and the results are illustrated in
Table 2.
Most of these aryl aldehydes tested here exhibited high reac-
tion activities (>80% yield) at room temperature but the selecti-
vity of rearrangement product was dependent on the structure of
the aldehyde. Firstly, all the aryl aldehydes with electron-donat-
ing substituent on the phenyl ring (2c–2h) gave complete
rearrangement products (3) which were determined by 1H NMR,
whether the substituent group was on the ortho, meta, or para
position. Other electron-rich aryl aldehydes such as 1-naphthyl
aldehyde 2u and 2-fural aldehyde 2v also led to the correspond-
ing carbamothioates 3. However, the product distribution for
electron-withdrawing aldehydes was unpredictable. 2-Pyridine-
carboxaldehyde 2w and paraformaldehyde 2x afforded only
O-thiocarbamates 4. For other aryl aldehydes it seems that the
presence of electron-withdrawing groups on the meta, or para
position (2j, 2k, 2m, 2n, 2p, 2q, 2s, 2t) did not influence the
O to S rearrangement, but the treatment of ortho-substituted
aromatic aldehydes 2i, 2l and 2r with imidazolium ylide 1
resulted in the formation of a mixture of carbamothioates 3 and
their structural isomers, non-rearranged O-alkyl partners 4. The
only exception is the reaction of 2-fluorobenzaldehyde 2o, which
only gave rearranged product 3o.
Scheme 3 Proposed mechanism.
Table 1 Reaction of imidazolium salt 1 with benzaldehyde 2aa
Entry
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8
DMSO
MeCN
DMF
THF
MeOH
Dioxane
DMF
DMF
DMF
DMF
DMF
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Cs2CO3
NaOH
KOAc
Et2NH
Pyridine
91
88
95
26
57
61
84
83
9
10
11
29
76
Trace
a Imidazolium salt (1, 5.0 mmol), benzaldehyde (2a, 5.0 mmol), base
(6.0 mmol), solvent (2.0 mL), reactions were carried out at 30 °C for
12 h. b Isolated yield.
These results indicate that this thermal O to S rearrangement is
very sensitive to the electron effects as well as the steric hin-
drance of the substituent on the phenyl ring. This phenomenon
is consistent with the widely accepted mechanism for NKR-like
reactions stating that the O to S rearrangement proceeds via a
efficient (entry 5). Solvent effects have proved that this reaction
may proceed via an ionic-type process.
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Table 2 Reaction of imidazolium salt 1 with arylaldehyde at room
temperaturea
Entry
Ar (2)
3 : 4b
Total yieldc (%)
1
2
3
4
5
6
7
8
2-MeC6H4 (2c)
3-MeC6H4 (2d)
4-MeC6H4 (2e)
2-MeOC6H4 (2f)
3-MeOC6H4 (2g)
4-MeOC6H4 (2h)
2-ClC6H4 (2i)
3-ClC6H4 (2j)
4-ClC6H4 (2k)
2-BrC6H4 (2l)
3-BrC6H4 (2m)
4-BrC6H4 (2n)
2-FC6H4 (2o)
3-FC6H4 (2p)
4-FC6H4 (2q)
2-NO2C6H4 (2r)
3-NO2C6H4 (2s)
4-NO2C6H4 (2t)
1-Naphthyl (2u)
2-Fural (2v)
>20 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
1 : 1
>20 : 1
>20 : 1
1.5 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
1 : 6
80
89
86
76
91
48
94
94
98
84
91
90
88
89
85
89
98
86
81
84
85
94
Scheme 5 The O to S rearrangement.
9
10
11
12
13
14
15
16
17
18
19
20
21
22d
Table 3 Reaction of aldehydes with imidazolium ylide 1 at different
temperaturesa
>20 : 1
>20 : 1
>20 : 1
>20 : 1
<1 : 20
<1 : 20
2-Pyridine (2w)
H (2x)
a Imidazolium salt (1, 5.0 mmol), aldehyde (2, 5.0 mmol), Et3N
(6.0 mmol), DMF (2.0 mL). b Determined by H NMR. c Isolated yield.
Entry Ar (2)
T (°C) t (h) Total yieldb (%) 3 : 4c
1
d Paraformaldehyde was used as the substrate.
1
2
3
4
5
6
2,6-Cl2C6H3 (2b) 30
2,6-Cl2C6H3 (2b) 60
2,6-Cl2C6H3 (2b) 100
12
48
12
24
24
24
98
94
64
82
83
79
<1 : 20
2.5 : 1d
>20 : 1
>20 : 1
>20 : 1
>20 : 1
four-membered 1,3-oxathietane transition state.17 In contrast
with the classic NKR of aryl groups, which is activated by elec-
tron-withdrawing substituents at the aromatic nucleus, the alkyl-
like version shows an inverse electronic situation.
2-ClC6H4 (2i)
2-BrC6H4 (2l)
2-NO2C6H4 (2r)
60
60
60
a Imidazolium salt (1, 5.0 mmol), aldehydes (2, 5.0 mmol), Et3N
(6.0 mmol), DMF (2.0 mL). b Isolated yield. c Determined by H NMR.
1
d Based on isolated products.
The transformation of 4 to 3 at room temperature was strongly
dependent on the electron property of the substrates. Electron-
rich aryl aldehydes possess higher electron density on the aryl
ring so that the intramolecular O to S displacement on the sp3
carbon was thermodynamically beneficial (Scheme 5), making
this transformation easy so that the substituent on the ortho pos-
ition did not affect the product distribution. For the electron-
deficient aryl aldehydes, the energy barrier of this step was
higher. The steric resistance could be significant when a rela-
tively large electron-withdrawing substituent such as Cl, Br, or
NO2 was in the ortho position. The fluorine atom is too small to
form a steric barrier for the addition of nucleophilic thiocarbonyl
to the sp3 carbon.
Based on the discussion above, we conclude that in order to
selectively obtain S-thiocarbamate 3, additional energy, for
example in the form of heat, to conquer this energy barrier is
needed. The reactions of 2,6-dichlorobenzaldehyde with the imi-
dazolium ylide at higher temperatures were then carried out
(Table 3). The results indicated that the equilibrium between 3
and 4 moved when the reaction temperature was increased. In
the case of 2,6-dichlorobenzaldehyde 2b, the ratio of the
rearranged product 3b to unrearranged product 4b was up to 2.5
when the reaction was carried out at 60 °C (Table 3, entry 2).
Further increasing the temperature to 100 °C led to almost 100%
selectivity for 3b, although the yield was relatively low probably
because of product decomposition at such high temperature
(Table 3, entry 3). A similar phenomenon could also be observed
when other aldehydes 2i, 2l and 2r, with an electron-withdraw-
ing substituent in the ortho position of the phenyl ring, were
used as substrates. Given the property of mono-substitution, the
corresponding energy barriers for them could be easier to over-
come compared to that of 2,6-dichlorobenzaldehyde. Thus, com-
plete rearranged products were observed when the reactions were
carried out at 60 °C. These results show that selectivity control
of this reaction is possible.
In conclusion, we have developed a new reaction between
N-thiocarbamate imidazolium ylide and arylaldehyde to afford
2-imidazolium alkylcarbamothioate bearing a wide diversity of
substitution patterns. The crucial step, oxygen to sulfur
rearrangement was strongly affected by the ortho-substitution on
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15 CCDC-880883 contains the supplementary crystallographic data for this
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