2(3H)-thiones with alkyl, allyl, and benzyl halides [1-4], namely boiling equimolar amounts of the thiones 1-4,
the chloroacetamides 5, and potassium carbonate in acetone (Table 1). It should be noted first of all that all of
these reaction gave the S-substituted derivatives exclusively.
X
X
H
N
N
N N
ClCH CONR'R''
R
R
+
2
S
SCH2CONR'R''
O
O
1–4
5a f
–
6a–f – 9a–f
1, 6 R = H, 2, 7 R = Me, 3, 8 R = Br, 4, 9 R = Cl; 1-3, 6-8 X = H, 4, 9 X = Cl;
5-9 a R' = Et, b R' = Bu, c-f R' = H; a R" = Et, b R" = Bu, c R" = cyclo-C6H11, d R" = Bu, e R" = Ph,
f R" = 2,5-Cl2C6H3
According to Table 1, the reaction of thiones 1-4 occurred successfully under these conditions with
N,N-dialkyl- (5a,b), N-cyclohexyl- (5c) and N-benzylchloroacetamides (5d) (in the last case only with thiones
1-3), with N-aryl-substituted chloroacetamides (5e,f) the products were obtained in relatively low yields only
after prolonged heating and only in the case of chloroacetamide 5e.
The nature of the substituent in the aromatic ring of the thione (see Table 1) under these conditions had
almost no effect on the yield of the reaction products, only in the case of thione 4 influence of two chlorine
atoms decreased the yield significantly in the reaction with the chloroacetamides 5d-f.
In order to increase the yield of compounds 6d,e-9d,e and with the hope of preparing compounds 6f-9f
we decided to carry out the reactions under more vigorous conditions – using alcoholic sodium hydroxide
solution as recommended in papers [5, 6] in place of potassium carbonate. However with the conditions used in
[5] (heating of the reagent mixture for 2 h at 60°C) the reactions of thiones 1-4 with the chloroacetamides 5e,f
did not give notable yields in our hands. This raises doubts about the high yields of products (not less than 75%)
claimed by the authors cited, since they used reagents analogous to ours – 5-(p-chlorophenyl)-1,3,4-
oxadiazoline-2-thione and N-arylchloroacetamides, where aryl is phenyl, p-Cl, Br, CH3, CH3O-phenyl, etc.
We obtained positive results only on prolonged boiling (15-30 h) of thiones 1-4 with chloroacetamides
5e,f in 10% ethanolic sodium hydroxide, and under these conditions the yield of the reaction product is
noticeable affected by substituents in both the thione and the chloroacetamide (Table 1). For example, with
thione 2 the yields of reactions products with chloroacetamides 5e,f were noticeably higher than in reactions
with thione 3. As for the relative reactivity of the N-substituted chloroacetamides, the influence of the nature of
the substituents on the yields of reaction products showed up markedly: with N-phenylchloroacetamide (5e) the
yields were considerably higher than with N-2,5-dichlorophenylchloroacetamide (5f).
The following conclusions can be drawn from the results obtained.
The yields of compounds 6a-f–9a-f depend directly on the nature of the substituent in the
chloroacetamide: the N-substituted chloroacetamides which we studied can be placed in the following order of
decreasing reactivity:
N,N-dialkyl- N-cycloalkyl- > N-benzyl- > N-arylchloroacetamides.
≥
The nature of the substituent in the thione molecule has no noticeable effect on the product yields in the
case of the reactive chloroacetamides 5a-d, whereas with compounds 5e,f the effect is shown clearly.
Products 6-9 were isolated as pure substances and were characterized via their UV and 1H NMR spectra.
Formation of S-substituted 5-aryl-1,3,4-oxadiazolinethiones is indicated by the presence of λmax in the
272-280 nm range in the UV spectrum, which is characteristic of S-derivatives [7]. N-Substituted products were
neither isolated nor even observed by TLC. This provides a basis for the conclusion that, while the nature of the
substituents in the molecules of both reagents determines the yields of the products, it has absolutely no effect
on the direction of the reaction.
1105
Galust'Yan
