The unique nucleophilic reactivity of arylaminochlorocarbenes†
Ying Cheng,*a Hua Yanga and Otto Meth-Cohn*b
a Department of Chemistry, Beijing Normal University, Beijing 100875, China.
E-mail: yincheng@95777.com; Tel: +861062205558
b Chemistry Department, Sunderland University, Sunderland, UK SR1 3SD.
E-mail: otto.meth-cohn@sunderland.ac.uk
Received (in Cambridge, UK) 15th October 2002, Accepted 11th November 2002
First published as an Advance Article on the web 26th November 2002
4-Methyl and 4-methoxyphenylaminochlorocarbene (read-
ily formed by deprotonation of the Vilsmeier reagent derived
from the corresponding N-methylformanilide with Hünig’s
base) reacted with diethyl acetylenedicarboxylate to give 1+2
quinoline adducts, while p-halophenylaminochlorocarbenes
yielded benzoazepine derivatives from 2+1 interaction of the
carbene with oxalyl chloride under the same reaction
conditions.
2 h, when after chromatography, red products were isolated
along with compound 5 and dimers 6.
Surprisingly, the structure of the red products derived from
4-methoxy- or 4-methyl-N-methylformanilide (1a and 1b
respectively) and diethyl acetylenedicarboxylate were totally
different from those derived from 4-halo-N-methylformanilides
1c–e. The NMR and MS spectroscopic data showed that the
former contained one arylaminochlorocarbene moiety and two
diethyl acetylenedicarboxylate units, while the latter required
two formanilide units but no diethyl acetylenedicarboxylate at
all. This was corroborated by the observation that the same
products were formed in the absence of diethyl acetylenedi-
carboxylate in the case of the haloformanilides. The structures
of these red products 7a (X = MeO) and 8c (X = F) were put
beyond doubt by X-ray crystallography‡ (Scheme 1).
The formation of the quinoline derivatives 7 could be
explained by a mechanism involving nucleophilic addition of
the aminochlorocarbene 10 to diethyl acetylenedicarboxylate 4,
cyclisation of the dipolar intermediate 11, a second nucleophilic
addition to 4 and finally rearrangement of the chloro-substituent
(Scheme 2).
The structure of the benzo[1,4]diazepine dicarboxylic anhy-
drides 8 is not sufficiently trivial to be explained by being
formed solely from the formanilide 1 and oxalyl chloride. As
with the formation of the quinolines 7, the formation of 8
appears to involve bis-addition of the carbene 10 to the oxalyl
chloride to form an iminium salt 16 and thence 17. The methyl
group adjacent to the iminium function is essentially similar to
one attached to a carbonyl function and can thus be easily
deprotonated allowing the new iminium ion 19 to cyclise to a
diazepine. The enamine 21 can then undergo nucleophilic
addition to oxalyl chloride at the less hindered carbon atom of
Carbenes can be divided into electrophilic, nucleophilic and
ambiphilic types according to their chemical behaviour. Whilst
dichlorocarbene is a typical electrophilic carbene, which readily
adds to alkenes, diaminocarbenes behave as nucleophiles in
their reactions with, for example, the N-phenylmaleimide,1
isocyanates and isothiocyanates.2 Several years ago,3 we
isolated a range of products derived from arylaminochlor-
ocarbenes, which were readily generated by deprotonation of a
Vilsmeier reagent with a tertiary amine. All of these products
derived from the aminochlorocarbene reacting firstly with the
parent Vilsmeier reagent to give the corresponding dimer in
high yields.3,4 We envisaged the reactivity of the amino-
chlorocarbenes to lie between that of a dichlorocarbene and a
diaminocarbene. They could be nucleophilic or ambiphilic. In
order to clarify the reactivity of aminochlorocarbenes, we
herein report our study of their reactions. They showed no
reactivity whatever towards simple alkenes or, for example,
benzoyl chloride but did react with diethyl acetylenedicarboxy-
late and with oxalyl chloride.
Diethyl acetylenedicarboxylate is reported to react with
nucleophilic carbenes, such as aminooxycarbenes,5 dioxy-
carbenes6 and aminothiocarbene.7 Initially, the Vilsmeier
reagent, derived from a 4-substituted N-methylformanilide 1
and oxalyl chloride 2, was deprotonated by Hünig’s base 3 in
dry chloroform or THF at 210 °C to 0 °C under a nitrogen
atmosphere. Addition of diethyl acetylenedicarboxylate 4 in the
same solvent, was followed by stirring at room temperature for
a period of time. However, under these conditions solely the
HCl adduct of diethyl acetylenedicarboxylate 5, together with
the carbene dimers 6 were recovered, indicating that the
‘dimerisation’ of the carbenes was much faster than its possible
reaction with 4. The hydrochloride salt of Hünig’s base (formed
in the reaction) was shown to react readily with 4 to give 5 in
high yield.
In order to minimise the dimerisation, a non-polar solvent
was used which would minimise the solubility of the Vilsmeier
reagent, and a much lower initial reaction temperature was
employed. Thus, the Vilsmeier reagent prepared by reaction of
a 4-substituted N-methylformanilide 1a–e and oxalyl chloride at
0 °C, was cooled to 278 °C. To this solid Vilsmeier reagent, a
solution of Hünig’s base in xylene was added with stirring to
1
form a suspension. After a ⁄2 h, diethyl acetylenedicarboxylate
4 in xylene was added and the temperature increased from 278
°C to room temperature during 2 h. The reaction mixture was
stirred at room temperature for 1 h and then at 50 °C for another
† Electronic supplementary information (ESI) available: experimental
details, characterization data for compounds
7 and 8. See http:/
Scheme 1
90
CHEM. COMMUN., 2003, 90–91
This journal is © The Royal Society of Chemistry 2003
Cheng, Ying
