Deamination of 3-(dialkylamino)-1,4-diarylhex-5-en-1-ynes during vacuum distillation

Article abstract of DOI:10.1134/S1070428017020063

During vacuum distillation of 3-(dialkylamino) derivatives of 1,4-diphenyl- and 4-phenyl-1-(p-chlorophenyl) hex-5-en-1-ynes deamination occurs resulting in a high yield of p-diarylbenzenes. The amines transformation into terbenzenes is a domino-reaction: first step consists in the β-elimination of secondary amines with the generation of conjugated dienyne which via an electrocyclic reaction transforms into cyclic allene intermediate. The latter after 1,3- or 1,5-hydride shift quickly converts into the final reaction products.

Full text of DOI:10.1134/S1070428017020063

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 2, pp. 178–183. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © E.О. Chukhajian, К.G. Shahkhatuni, El.О. Chukhajian, L.V. Ayrapetyan, G.А. Panosyan, 2017, published in Zhurnal Organicheskoi
Khimii, 2017, Vol. 53, No. 2, pp. 191–195.
Deamination of 3-(Dialkylamino)-1,4-diarylhex-5-en-1-ynes
During Vacuum Distillation
E. О. Chukhajian, К. G. Shahkhatuni, El. О. Chukhajian,
L. V. Ayrapetyan, and G. А. Panosyan*
Scientific and Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of the Republic of Armenia, Institute of Organic Chemistry,
pr. Azatutyana 26, Yerevan, 0014 Armenia
*e-mail: qnarsh@yandex.ru
Received April 6, 2016
Abstract—During vacuum distillation of 3-(dialkylamino) derivatives of 1,4-diphenyl- and 4-phenyl-1-(p-
chlorophenyl)hex-5-en-1-ynes deamination occurs resulting in a high yield of p-diarylbenzenes. The amines
transformation into terbenzenes is a domino-reaction: first step consists in the β-elimination of secondary
amines with the generation of conjugated dienyne which via an electrocyclic reaction transforms into cyclic
allene intermediate. The latter after 1,3- or 1,5-hydride shift quickly converts into the final reaction products.
DOI: 10.1134/S1070428017020063
Many molecular rearrangements of organic
compounds are known, in particular, those of
unsaturated ammonium salts, among them the
rearrangement-cleavage [1], intramolecular cyclization
[2]. Basic results of these studies are generalized in
reviews [3–5]. Special place among them belongs to
Stevens rearrangement [6] proceeding through
intermediate formation of ammonium ylides. This is
due to the ammonium ylides capability to undergo
transformations with the formation of functionally
substituted tertiary amines. Stevens rearrangement,
along with its fundamental value, provides wide
opportunities for the synthesis of amines of various
structures of practical value. For instance, unsaturated
amines and quaternary ammonium salts of various
structures are present in the molecules of drugs,
fungicides, pesticides, metal corrosion inhibitors,
surfactants, washing and desinfecting agents etc.
Considering the above information, bringing new
unsaturated ammonium salts into Stevens
rearrangement providing wide opportunities for the
synthesis of new potentially bioactive tertiary amines,
is a topical issue.
It is known that Stevens rearrangement of dialkyl(but-
2-en-1-yl)(3-phenylprop-2-yn-1-yl)ammonium bromi-
Scheme 1.
_
HO
R2N+
X
X
R2N+
X
_
CH2OH
CH2OH
X
X
R2N
R2N
_
_
R2N
O
O
O
A
R = Me, Ph
178

DEAMINATION OF 3-(DIALKYLAMINO)-1,4-DIARYLHEX-5-EN-1-YNES DURING VACUUM
179
Scheme 2.
_
_
R2HN
HO
HO
R2N+
R2N+
X
_
X
X
Ph
1a_1h
2a_2h
X = H: R = Me (a), Et (b), Pr (c); R2 = (CH2)4 (d), (CH2)5 (e), (CH2)2O(CH2)2 (f); X = Cl,
R2 = (CH2)5 (g), (CH2)2O(CH2)2 (h).
des is followed by the conversion of the migrating
group [7]. Recently it was established that similar deri-
vatives in aqueous alkaline surroundings prevailingly
underwent Stevens rearrangement, including the
conversion of the migrating group and the transfer of
the reaction center in the accepting group with the
formation of intermediate allenic aminoalcohols А
(Scheme 1). The intramolecular cyclization of the
latter through О-alkylation results in amino derivatives
of dihydrofuran. The observed reaction is the only
known case for Stevens rearrangements [8, 9].
In continuation of the investigations of this
rearrangement we explored the behavior of dialkyl(3-
phenylprop-2-en-1-yl)(3-phenylprop-2-yn-1-yl)ammo-
nium bromides 1а–1f [10] and (3-phenylprop-2-en-1-
yl)[3-(4-chlorophenyl)prop-2-yn-1-yl]piperidinium
and morpholinium bromides 1g and 1h [11]. Salts
1а–1h under the action of two equiv of KOH in the
presence of few drops of methanol rearranged with self-
heating into 3-(dialkylamino)-1,4-diarylhex-5-en-1-
ynes 2a–2h, yellowish viscous fluids, in 60–65% yield
(Scheme 2).
Scheme 3.
Ph
Me
1,2-elimination
1,6-elimination
Ph
R2N
Ph
_
HO
_
HO
3a, 3c
R2N+
R2N+
_
_
Ph
Br
Br
Ph
R2N
1a, 1c
Me
Me
4a, 4c
Ph
1,6-elimination
1,2-elimination
Ph
Et2N
Ph
_
_
5b
HO
HO
Et2N+
Et2N+
_
_
Ph
Br
Br
Ph
Et2N
1b
Me
6b
R = Me (a), Et (b), Pr (c).
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CHUKHAJIAN et al.
180
Scheme 4.
R2N
X
X
2a_2h
7, 8
X = H (7), Cl (8).
1
In case of salts 1а–1с along with Stevens rearrange-
ment, which is the main direction of interaction, reactions
of cyclization-cleavage also occur leading to the
formation of a mixture of 3-[(dialkylamino)methyl]-2-
methyl-1-phenylnaphtalenes 3а, 3с, and 5b and 3-
methyl-2-[(dialkylamino)methyl]-1-phenylnaphtalenes
4а, 4с, and 6b (Scheme 3) in overall yields 13–15%.
Basing on IR and Н NMR spectra we concluded
that the Stevens rearrangement of salts 1а–1h was
usually accompanied with the conversion of migrating
group.
Unlike the 1-allyl-1-dialkyl(3-phenylprop-2-yn-1-
yl)-, (but-1-en-2-yl)-1-dimethyl(3-phenylprop-2-yn-1-
yl)amines [7] and their methallyl analogs [12] amines
2а–2h during vacuum distillation undergo deamina-
tion, and as final products we obtained p-diphenylben-
zene 7 [13, 14] and p-phenyl-p-chlorophenylbenzene 8
in 65 and 61% yields correspondingly (Scheme 4).
1
Physicochemical characteristics and Н and 13С NMR
spectra of amines mentioned above are identical to the
data for compounds that are generated during aqueous-
alkaline cleavage of cyclization products of salts 1а–1с
in conditions of basic catalysis [10].
Deamination of amines 2а–2h occurred within 20–
25 min. Compounds with simple alkyl groups at the
nitrogen atom suffer deamination at higher tempe-
ratures: 2а, at 142°C (1.5–2 mmHg); 2b, 142°C (1–
1.5 mmHg); 2c, 75°C (1 mmHg); 2d, 45–50°C
(2 mmHg); 2e and 2f, 50–55°C (2–3 mmHg); 2g, 110°C
(1–2 mmHg); 2h, 70–75°C (3–4 mmHg).
Before vacuum distillation of the obtained mixtures
their IR spectra were recorded. In IR spectra typical
absorption bands are present at 1580, 3030 (aromatic
ring), 730, 690 (mono-substituted benzene ring) (2а–
2h, 3а, 3с, 4а, 4с, 5b, and 6b) and at 810, 840 cm–1
(para-substituted benzene ring) (2g and 2h), and also
absorption bands of the terminal vinyl group at 1630,
960, 920 (2а–2h) and 870, 770, 730 cm–1 (penta- and
1,2-substituted benzene ring) (3а, 3с, 4а, 4с, 5b, and
6b).
During vacuum distillation of mixture of amines
2a, 2c, 3a, 3c, 4a, 4c, and 2b, 5b, 6b crystals of p-
diphenylbenzene 7 deposited in the side arm of Claisen
flask and impeded the distillation of mixture of amines
3a, 3c, 4a, 4c, and 5b, 6b. To avoid this difficulty the
distillation of the mixture of amines 2a, 2c, 3a, 3c, 4a,
1
Analysis of the Н NMR spectrum of compounds
2а–2h demonstrates that the structure with the terminal
vinyl group prevails in the mixture.
Scheme 5.
H
X
Δ
X
_
R2NH
R2N
2a_2h
B
[1,3]- or [1,5]-H shift
X
X
7, 8
H
X = H (7), Cl (8).
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DEAMINATION OF 3-(DIALKYLAMINO)-1,4-DIARYLHEX-5-EN-1-YNES DURING VACUUM
181
Scheme 6.
R1
R1
R2
R3
R1
R2
NMe2
[3,3]
[1,3]-H shift
R3
H
R2
Ph
Ph
R3
NMe2
Ph
H
NMe2
9
10
R1
R1
R3
R2
R2
NMe2
R3 = H
_
NHMe2
Ph
Ph
H
11
12
4c, and 2b, 5b, 6b was carried out in a flask with a
central tube and a collar. During the vacuum
distillation in the central tube of the flask crystals of
compound 7 were collected, and in the collar, the
mixture of amines 3a, 3c, 4a, 4c, or 5b, 6b that were
products of cyclization-cleavage [10]. Physicochemi-
in high yields was developed. The formation of these
two compounds is a good chemical proof that Stevens
rearrangement of salts 1а–1h is mainly realized by
conversion of migrating group. It is known that
compound 7 is a high-temperature carrier and initial
compound for preparation of polyphenyls [13]. The
1
1
cal characteristics and Н, 13С NMR spectra of amines
structure of compounds 7 and 8 was confirmed by Н
3a, 3c, 4a, 4c, and 5b, 6b are identical to the data for
amines that form at cleavage of cyclization products of
salts 1а–1с in conditions of basic catalysis [10]. The
occurrence of cyclization-cleavage in conditions of
Stevens rearrangement is a unique case [15, 16].
and 13С NMR spectra.
As it is known, 3-(dimethylamino)-1,4-diphenylhex-
5-en-1-yne 2а, obtained as a result of Stevens rearran-
gement of dimethyl(3-phenylprop-2-en-1-yl)(3-phenyl-
prop-2-yn-1-yl)ammonium bromide 1а, at heating in
xylene during 1 h affords terphenyl 7 in 70% yield
[14]. It was established in the same study that at
heating the other similar products of Stevens rearran-
gement [for example, 3-(dimethylamino)-4-(or -5-)-
methylhex-5-en-1-yne at 200°C during 3 days or 12 h
respectively and -5-phenyl-hex-5-en-1-yne at 140°С
during 3 days in an evacuated sealed tube] biphenyles
were obtained as final products. In experimental
conditions of [14] it is hard to prove in which step the
elimination of secondary amine occurs and therefore it
is hard to determine the sequence of stages of
biphenyls generation. Nevertheless Laird et al. [14]
offered two schemes of biphenyls formation, and one
of them coincides with Scheme 5 above. However they
consider as impossible the generation of cyclic allene
intermediate.
The vacuum distillation of amines 2d–2h was
performed in a standard Claisen flask. Crystals 7 and 8
deposited in the side arm were collected mechanically.
We suggest a scheme of formation of compounds 7
and 8 (Scheme 5), according to which amines 2а–2h
during vacuum distillation undergo β-elimination first
with elimination of secondary amines and simulta-
neous generation of 1,4-diarylhexa-3,5-dien-1-ynes B,
in molecules of which diene and dienophile groups are
present that quickly undergo thermal intramolecular
cyclization, resulting in compounds whose molecules
contain a middle ring with an allene group. Cyclic
compounds with an allene group are very unstable, so
they quickly isomerize transforming into terphenyls 7
and 8.
The discovered deamination of amines 2а–2h
during vacuum distillation is a unique case in organic
chemistry and has a general character. Along with a
fundamental it also has a practical value: thus a new
accessible method of obtaining the terphenyls 7 and 8
According to Scheme 6 offered in [14] [3,3]-
sigmatropic rearrangement of amines may result in
allenamine 9, from which by [1,3]-hydrogen shift
hexatriene 10 is generated. Electrocyclic reaction of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 2 2017

CHUKHAJIAN et al.
182
the latter results in compound 11, from which after
elimination of dimethylamine biphenyl 12 is formed.
aqueous KOH, and extracted with ether (3 × 40 mL).
The extract was washed with water and dried with
MgSO4.
A good proof that deamination occurs first and then
follows the cyclization of intermediate compounds B
(Scheme 5) was as follows: at heating 3-(dimethyl-
amino)-1,4-diphenylhex-5-en-1-yne 2а in experimental
conditions of [14] we clearly noticed during10–15 min
the liberation of dimethylamine that was absorbed with
solution of gaseous НCl in anhydrous ether. After
finishing the experiment and maintaining the reaction
mixture at room temperature terphenyl 7 was filtered
from xylene, and decanting of the ether made it
possible to separate dimethylamine hydrochloride that
was washed with anhydrous ether and dried over Р2О5.
This salt melted at 171°С and did not provide a
depression of the melting point when mixed with an
authentic sample.
After removing the ether the residual mixture of
amines 2а, 2с, 3а, 3с, 4а, 4с, 2b, 5b, 6b, and 2d–2h
was subjected to vacuum distillation. General method.
Into a flask with a central tube and a collar were placed
asbestos fibers operating as capillaries, 6 mmol of the
mixture of amines 2а–2с, 3а, 3с, 4а, 4с, and 5b, 6b
was charged and subjected to the vacuum distillation.
After completing the process of deamination of amines
2а–2с and formation of terphenyl 7 which was
collected in the central tube, the distillation started of
the mixture of amines 3а, 3с, 4а, 4с or 5b, 6b that
were collected in the collar. Crystals of compound 7
were removed mechanically from the central tube, and
from the collar with the assistance of a capillary the
mixture of 0.78–0.9 mmol of amines 3а, 3с, 4а, 4с,
and 5b, 6b [10] was isolated in an overall yield of 13–
15%.
The phenomenon of deamination of amines 2а–2h
during vacuum distillation has a general character and
results in the formation of terphenyls 7 and 8. This is a
good chemical proof that Stevens rearrangement of
salts 1а–1h is mainly realized with the conversion of
migrating group.
Vacuum distillation of amines 2d–2h (6 mmol) was
performed in a standard Claisen flask. In the side arm
crystals of compounds 7 or 8 were collected that were
mechanically removed. After that the crystals and the
rest of the Claisen flask were washed with anhydrous
ether, the crystals of compounds 7 and 8 were filtered
off. After evaporating ether we obtained an
insignificant amount of amine products that we failed
to identify.
EXPERIMENTAL
Synthesis and physicochemical characteristics of
the initial salts 1а–1h and amines 3a, 3c, 4a, 4c, and
5b, 6b are described in [10, 11]. IR spectra of amines
2а–2h, 3a, 3c, 4a, 4c, 5b, 6b were recorded on a
spectrometer Specord 75 IR from thin layer, and of
compound 8, from solution in CHCl3. 1Н and 13С NMR
spectra of compounds 7 and 8 were obtained on an
instrument Varian Mercury 300 VX (300 and 75 МHz
correspondingly) at 303 K in a mixture of DMSO-d6–
CCl4, 1 : 3, internal reference TMS.
Salts 1а–1h and amines 3а, 3с, 4а, 4с, 5b, and 6b
were described in [10, 11].
1,1':4',1''-Terphenyl (7). Yield 0.9 g (3.9 mmol,
1
65%), white crystals, mp 210°С (xylene) [13]. Н
NMR spectrum, δ, ppm: 7.31 m (2H, H4 Ph), 7.42 m
(4H, H3,5 Ph), 7.61 m (4H, H2,6 Ph), 7.66 s (4H, C6H4).
13C NMR spectrum, δ, ppm: 126.3 (4CH), 126.7 (2CH,
C4 Ph), 126.8 (4CH), 128.2 (4CH), 139.3 (2C), 139.9
(2C).
Stevens rearrangement of dialkyl(3-arylprop-2-
en-1-yl)(3-arylprop-2-yn-1-yl)ammonium bromides
(1а–1h). General method. To a thoroughly stirred
mixture of 8 mmol of powdered salt 1а–1h and 1.46 g
(16 mmol) of powdered KOH few drops of methanol
was added. Reaction proceeded with self-heating. After
30–40 min the mixture was extracted with diethyl ether
(2 × 50 mL). Ether extract was washed with water. An
aliquot of ether extract while shaking with water was
titrated with 0.1 N H2SO4. The titration showed the
presence of 5.2–5.4 mmol of amine (yield 65–67%) in
the extract. The extract was acidified with 20% HCl.
The water layer was separated, neutralized with 10%
4-Chloro-1,1':4',1''-terphenyl (8). Yield 0.96 g
(3.66 mmol, 60%), yellow crystals, mp 205°C (xylene)
[17]. IR spectrum, ν, cm–1: 1580 (aromatic ring), 820
(p-substituted benzene ring), 720, 680 (mono-substitu-
1
ted benzene ring). Н NMR spectrum, δ, ppm: 7.32 m
(1H, H4 Ph), 7.39–7.45 m (4H, H3,5 Ph and C6H4Cl),
7.59–7.63 m (4H, H2,6 Ph and C6H4Cl), 7.65 s (4H,
C6H4). 13C NMR spectrum, δ, ppm: 126.3 (2CH), 126.7
(2CH), 126.8 (CH), 126.9 (2CH), 127.7 (2CH), 128.2
(2CH), 128.3 (2CH), 132.5, 137.9, 138.4, 139.6, 139.7.
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DEAMINATION OF 3-(DIALKYLAMINO)-1,4-DIARYLHEX-5-EN-1-YNES DURING VACUUM
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