Reaction of amides of 2,3-dibromopropionic and 2-bromoacrylic acids with pyridine and triphenylphosphine

Article abstract of DOI:10.1134/S1070363209040148

By refluxing pyridine with 2,3-dibromopropionic acid amide in acetonitrile, amide of 3-bromo-2-pyridiniumbromidopropionic acid I was synthesized. The latter is inert toward the second molecule of pyridine under the used conditions. Compound I was found to

Full text of DOI:10.1134/S1070363209040148

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 4, pp. 759–761. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © R.Dzh. Khachikyan, N.V. Tovmasyan, M.G. Indzhikyan, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 4,
pp. 595–597.
Reaction of Amides of 2,3-Dibromopropionic
and 2-Bromoacrylic Acids with Pyridine
and Triphenylphosphine
R. Dzh. Khachikyan, N. V. Tovmasyan, and M. G. Indzhikyan
Institute of Organic Chemistry, National Academy of Sciences of Armenia,
ul. Zakariya Kanakertsy 167-A, Yerevan, 375091 Armeniya
fax: (374+1)283511
e-mail: nara7777@mail.ru
Received October 2, 2008
Abstract―By refluxing pyridine with 2,3-dibromopropionic acid amide in acetonitrile, amide of 3-bromo-2-
pyridiniumbromidopropionic acid I was synthesized. The latter is inert toward the second molecule of pyridine
under the used conditions. Compound I was found to react with triphenylphosphine to form a mixture of 3-
triphenylphosphoniumbromidopropionitrile II and 1-triphenylphosphoniumbromido-2-pyridiniumbromido-
ethane III. Schemes of reactions were suggested involving attack of phosphine on the carbonyl group as the
first stage. The reaction of α-bromoacrylic acid amide with triphenylphosphine was shown to yield also
compound II. Evidently, this reaction proceeds through intermediate formation of enolphosphonium salt.
DOI: 10.1134/S1070363209040148
It was established earlier that dibromopropionic
acid and its nitrile, esters, and amide react with
triphenylphosphine by a common scheme, the first
stage of which is debromination [1]. By contrast,
reactions of this acid as well as its chlorine analog with
aliphatic amines result in dehydrobromination
products, and the reaction with pyridine yields
vynilpyridinium halides. The latter are formed as a
result of the substitution at the α-carbon atom followed
by dehydrohalogenation and decarboxylation [1].
Salt I was involved into the reaction with
triphenylphosphine in boiling acetonitrile. The results
1
were unexpected. According to the H NMR spectral
data, a mixture of 3-triphenylphosphoniumbromide-
propionitrile II, 1-triphenylphosphoniumbromido-2-
pyridiniumbromidoethane III, and triphenylphosphine
oxide was obtained rather than the expected products
of dehydrobromination and nucleophilic substitution.
In the spectra signals characteristic of the amide
moiety are absent. We believe compounds II and III to
form according to Schemes 1 and 2.
In the present work we examined reactions of
pyridine with dibromopropionic acid amide. The
equimolar mixture refluxed in acetonitrile gave rise to
amide of 3-bromo-2-pyridiniumbromidopropionic acid
I in 87% yield. The situation did not change at the ratio
The first scheme leading to compound II involves
substitution of the bromine atom with triphenyl-
phosphine followed by the attack of phosphine on the
amide oxygen atom, by pyridine elimination and the
subsequent stages of nucleophilic substitution with
ionic bromine, dehydrobromination, and prototropic
isomerization.
1
:2 indicating that under the used conditions the β-
bromine atom is inert relative to the pyridine.
O
O
According to the second scheme, O-betaine under-
goes further transformations by successive elimination
of triphenylphosphine and ammonia under the action of
water (evidently, from solvent) to form compound III.
CH2 CH
Br
Br
C
+
CH2 CH C
−
NH2
N
Br
N+ Br
NH2
We also carried out a reaction of triphenyl-
phosphine with 2-bromoacrylic acid amide IV at the
I
759

7
60
KHACHIKYAN et al.
Scheme 1.
−
+
O
OP(C H )
6 5 3
H
C
+
+
I + (C H ) P
(C H ) P CH
C
P(C H )
(C H ) P CH CH
C
6 5 3
2
6
5 3
6
5 3
2
6
5 3
−
−
Br− NH2
Br
Br
N
Ν
Br−
NH2
+
Br
+
+
+
(
C H ) P CH CH
C
(C H ) P CH CH
C
NH
(C H ) P CH2 CH2
C
N
6
5 3
2
6
5 3
2
6 5 3
−HBr
−
(C H ) P
O
−
−
Br−
6
5 3
Br
Br
NH2
II
Scheme 2.
P(C H )
+
+
6
5 3
P(C H )
P(C H )
6
5 3
6
5 3
O
H O
2
+
+
O−
+
(
C H ) P CH CH
C
(C H ) P CH CH
C
(C H ) P CH CH
C
OH
6
5 3
2
6
5 3
2
6
5 3
2
−
−
−
Br− NH2
Br− NH2
Br
Br
Br
N
N
−OH
N
NH2
Br−
+
+
+
OH
C
O
+
+
(
C H ) P CH CH
OH
(C H ) P CH CH
C
Br−
OH
6
5 3
2
6
5 3
2
−
(C H ) P
−
−NH
3
−
6
5 3
Br
Br−
Br
N
NH2
N
+
+
+
+
(
C H ) P CH2 CH2
Ν
6
5 3
−CO2
−
Br−
Br
III
component ratio 1:1 under the above conditions. In this
case reaction was shown to proceed also through attack
of phosphine on carbonyl group yielding compound II
Amide of 2-bromoacrylic acid IV was prepared by
the reaction of amide of 2,3-dibomopropionic acid
with equimolar amount of triethylamine under heating,
yield 83%. Based on the data obtained it may be
(
Scheme 3).
Scheme 3.
P(C H )
6
5 3
+
O
OP(C H )
6
5 3
−
H C
2
C
C
CH2 CH
C
Br
CH2
C
C
NH2
−
(C H ) P
O
6
5 3
NH2
NH2
Br
Br
IV
Br
(
C H ) P, HBr
+
6
5 3
CH2 CH
C
CH2 CH
C
N
(C H ) P CH2 CH2
6
5 3
C
N
−HBr
Br−
NH
II
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 4 2009

REACTION OF AMIDES OF 2,3-DIBROMOPROPIONIC
761
concluded that aliphatic amines react with the
mentioned amide by the dehydrobromination scheme,
i.e., similarly to dibromopropionic acid, its esters and
nitrile.
depression of melting point in the mixture with an
authentic sample).
b. The components ratio 1:2. A mixture of 0.46 g of
salt I and 0.78 g of triphenylphisphine was refluxed in
acetonitrile for 20 h. After filtring off 0.1 g (20%) of
salt I and treating the filtrate as described above, 0.4 g
of the mixture of salts II and III was obtained in the
EXPERIMENTAL
1
31
The Н and Р NMR spectra were recorded on a
1
31
ratio 1:1 in an overall yield 58%. The Н and Р NMR
Varian MERCURY-300 instrument; operating frequency
spectra were as those given above.
3
00 МHz; internal reference TMS.
After the solvent was removed from the aceto-
nitrile–ether filtrate, triphenylphosphine oxide was
obtained. Yield 0.4 g (50%), mp 154°С (without
depression of melting point in the mixture with an
authentic sample).
3
-Bromo-2-pyridiniumbromidopropionic
acid
amide (I). A mixture of 1.85 g of 2,3-dibromo-
propionic acid amide and 0.63 g of pyridine in
acetonitrile was refluxed for 20 h. The formed
precipitate was filtered off, washed thoroughly with
acetonitrile, and dried in a vacuum. Yield 2.15 g
2-Bromoacrylic acid amide (IV). A mixture of
0.5 g of 2,3-dibromopropionic acid amide and 0.2 g of
triethylamine in ether was heated for 8 h. The
precipitate of 0.35 g of mixture of the unreacted initial
amide and the formed triethylamine hydrobromide was
filtered off. Then ether was evaporated and residue
was dried in a vacuum. Yield 0.25 g (83%), mp above
1
(
87%), mp 205°С. Н NMR spectrum (DMSO-d +
6
ССl 1:3), δ, ppm: 5.10–5.38 m (3Н, –СН–СН –); 7.40
4
2
br.s (1Н, NН ); 7.96 br.s (1Н, NН ); 8.20 d. d (2Н, m-
2
2
Нpyridine, J 7.8 Hz, J 6.4 Hz); 8.70 t. t (1Н, p-Нpyridine,
1
2
J 7.8 Hz, J 1.2 Hz); 9.35 d. d (2Н, о-Нpyridine, J1
1
2
6
.4 Hz, J 1.1 Hz). Found, %: С 30.87; Н 3.60, Br
2
1
5
1.80; N 9.20; С Н Br N О. Calculated, %: С 30.97;
240°С. Н NMR spectrum (DMSO-d + ССl 1:3), δ,
8
10
2
2
6
4
Н 3.20; Br 51.60; N 9.00.
ppm: 6.0 s (1Н, СН ); 6.65 s (1Н, СН ); 7.3 br.s (1Н,
2 2
NН ); 7.25 br.s (1Н, NН ). Found, %: С 24.45; Н 2.81,
2
2
Reaction of salt I with triphenylphosphine: а.
The components ratio 1:1. A mixture of 0.46 g of I and
Br 53.46; N 9.26; С Н BrNО. Calculated, %: С 14.00;
3
4
Н 2.66; Br 53.33; N 9.33.
0
.39 g of triphenylphosphine was refluxed in aceto-
nitrile for 20 h. After filtrating of 0.2 g (44%) of the
unreacted salt, the filtrate was poured into ether. The
precipitate was filtered off, washed thoroughly with
ether, and dried in a vacuum. Yield 0.15 g of the
mixture of 3-triphenylphosphoniumbromidopropio-
nitrile II and 1-triphenylphosphoniumbromido-2-pyri-
diniumbromidoethane III in the ratio 1:1 in an overall
3-Triphenylphosphoniumbromidopropionitrile
(II). A mixture of 0.15 g of IV and 0.26 g of triphenyl-
phosphine was refluxed in acetonitrile for 20 h. The
acetonitrile filtrate was poured into ether. The
precipitate was filtered off, washed thoroughly with
ether, and dried in a vacuum. Yield 0.1 g (25.25%), mp
1
31
210°С. The Н and Р NMR spectra are the same as
given above. Found, %: С 63.75; Н 4.82; Br 20.42; N
1
yield 22%. Н NMR spectrum of II (DMSO-d + ССl
6
4
1
:3), δ, ppm: 2.60 m (2Н, СН СN); 3.86 m (2Н,
3.62; Р 7.92. С21Н19BrNР. Calculated, %: С 63.64; Н
4.79; Br 20.20; N 3.54; Р 7.82.
2
3
1
СН Р); 7.74–7.93 m (15Н, С Н ). Р NMR spectrum,
2
6
5
δ, ppm: 30.65.
After the solvents were removed from the
acetonitrile-ether filtrate and the residue was treated
with water, triphenylphosphine oxide was obtained.
Yield 0.2 g (70%), mp 154°С (without depression of
melting point in the mixture with an authentic sample).
1
Н NMR spectrum of III (DMSO-d + ССl 1:3), δ,
6
4
ppm: 2.88 m (2Н, NСН ); 4.30 m (2Н, РСН ); 7.65–
2
2
7
7
1
.74 m (15Н, С Н ); 8.00 d.d (2Н, m-Нpyridine, J1
6 5
.8 Hz, J 6.4 Hz); 8.50 t.t (1Н, p-Н
, J 7.8 Hz, J
1 2
2
pyridine
.2 Hz); 9.00 d. d (2Н, о-Нpyridine, J 6.4 Hz, J 1.1 Hz).
1
2
3
1
REFERENCES
Р NMR spectrum, δ, ppm: 29.36.
After the solvent was removed from the aceto-
nitrile–ether filtrate, triphenylphosphine oxide was
obtained. Yield 0.2 g (50%), mp 154°С (without
1
.
Khachikyan, R.Dzh., Tovmasyan,N.V., and Indzhi-
kyan, M.G., Zh. Obshch. Khim., 2005, vol. 75, no. 12,
p. 1978.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 4 2009