Stereochemistry of macrocyclization of cis-4-cyclohexene-1,2-dicarboxylic acid with dihalogen derivatives

Article abstract of DOI:10.1023/A:1020826317894

Stereochemistry of [2+2]- and [1+1]-macrocylization of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,2-dibromoethane, 1,3-dichloro-2-propanol, and 1,5-dichloro-3-oxapentane was studied. The reaction of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,2-dibromoethane according to the [2+2]-cyclization scheme gave a mixture of stereoisomeric macroheterocycles with cis,syn,cis- and cis,anti,cis-junction of the polyether and cyclohexene rings. In the reaction of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,5-dichloro-3-oxapentane, a mixture of crown compounds with cis,anti,cis- and cis-junction of the polyether and cyclohexene rings was obtained. The structure of the products was established on the basis of their chemical transformations and spectral data.

Full text of DOI:10.1023/A:1020826317894

Russian Journal of Organic Chemistry, Vol. 38, No. 7, 2002, pp. 1060 1063. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 7, 2002,
pp. 1103 1106.
Original Russian Text Copyright
2002 by Shabanov, Gasanova, Mamedov.
Stereochemistry of Macrocyclization of cis-4-Cyclohexene-
1,2-dicarboxylic Acid with Dihalogen Derivatives
A. L. Shabanov, M. M. Gasanova, and Ch. I. Mamedov
Geotechnology Problems of Petroleum, Gas, and Chemistry Research Institute, Azerbaidjan State
Petroleum Academy, pr. Azadlyg 20, Baku, 370601 Azerbaidjan
Received September 14, 2001
Abstract Stereochemistry of [2+ 2]- and [1+ 1]-macrocylization of cis-4-cyclohexene-1,2-dicarboxylic acid
with 1,2-dibromoethane, 1,3-dichloro-2-propanol, and 1,5-dichloro-3-oxapentane was studied. The reaction of
cis-4-cyclohexene-1,2-dicarboxylic acid with 1,2-dibromoethane according to the [2+ 2]-cyclization scheme
gave a mixture of stereoisomeric macroheterocycles with cis,syn,cis- and cis,anti,cis-junction of the polyether
and cyclohexene rings. In the reaction of cis-4-cyclohexene-1,2-dicarboxylic acid with 1,5-dichloro-3-oxa-
pentane, a mixture of crown compounds with cis,anti,cis- and cis-junction of the polyether and cyclohexene
rings was obtained. The structure of the products was established on the basis of their chemical transforma-
tions and spectral data.
We previously found that o-mercaptophenols react
with symmetric 2,2 -dichloro- and 2,2 -dibromodiethyl
ethers according to the [2+2]-cyclization scheme,
leading to formation of compound I with symmetric
arrangement of the sulfur atoms [1, 2]. By contrast,
reactions of o-mercaptophenols with unsymmetrical
2-haloethyl 2-halo-1-alkylethyl ethers give macro-
heterocycles II with unsymmetrical arrangement of
the sulfide sulfur atoms and alkyl groups [2].
(III) with 1,2-dibromoethane, 1,3-dichloro-2-propanol,
and 1,5-dichloro-3-oxapentane. The reaction of di-
potassium cis-4-cyclohexene-1,2-dicarboxylate with
1,2-bromoethane in anhydrous butanol follows the
[2 + 2]-cyclization scheme and gives a mixture of
cis,syn,cis- and cis,anti,cis-polyesters V and VI
(Scheme 1). Isomers V and VI were isolated by
vacuum distillation in combination with column
chromatography (Rf 0.23 and 0.30, respectively;
Silufol plates, hexane chloroform, 2:1). The isomer
ratio is 1:1. Compound V crystallizes on storage.
The IR spectra of V and VI contain strong absorp-
1
tion bands at 1732 and 1736 cm , respectively, which
belong to the ester fragments. The double bonds in
cis,syn,cis-isomer V give only one IR absorption band
1
with its maximum at 1642 cm , whereas in the spec-
trum of cis,anti,cis isomer VI two strong bands are
1
observed at 1640 and 1660 cm due to steric non-
equivalence of the double bonds.
Both isomers V and VI undergo hydrolysis in
alkaline medium to afford cis-dicarboxylic acid III
which is almost quantitatively converted into the cor-
responding cis-anhydride by heating in boiling acetyl
chloride [4]. These data indicate that no cis trans
isomerization of III occurs in the course of formation
of macroheterocycles V and VI. The molecular weight
of isomeric products V and VI was determined by
mass spectrometry (M+ 392 amu). Their fragmentation
under electron impact follows the retro-Diels Alder
We have studied the stereochemistry of macro-
cyclization of cis-4-cyclohexene-1,2-dicarboxylic acid
1070-4280/02/3807-1060$27.00 2002 MAIK Nauka/Interperiodica

STEREOCHEMISTRY OF MACROCYCLIZATION OF cis-4-CYCLOHEXENE-.. .
1061
Scheme 1.
decomposition scheme and gives rise to macrocyclic
fragment ion VIII with m/z 284 [5]. The molecular
weights of V and VI were also determined by iodo-
metric titration.
The purity of compound IX was checked by TLC
on Silufol plates, and its structure and configuration
were confirmed by physical methods and chemical
transformations. The IR spectrum of IX contains
1
strong absorption bands at 3744 and 3456 cm ,
which are typical of hydroxy group. A strong absorp-
1
tion band with its maximum at 1736 cm belongs
to stretching vibrations of the lactone carbonyl groups.
Alkaline hydrolysis of compound IX gave only cis-
4-cyclohexene-1,2-dicarboxylic acid (III) which was
identical to a sample obtained by heating of the corre-
sponding anhydride in boiling water [3, 5].
We also examined the reaction of dipotassium salt
IVa with 1,5-dichloro-3-oxapentane which followed
the [2+2]-cyclization scheme. Unlike the reaction
with 1,2-dibromoethane, we obtained a mixture of
macrocyclic compounds X and XI with cis- and
Unlike the reaction of dipotassium salt IVa with
1,2-dibromoethane ([2+2]-cyclization scheme), mono-
potassium salt IVb reacts 1,2-dibromoethane in two
steps according to the [1+1] scheme to afford only
one cis,syn,cis isomer V (Scheme 1). As might be
expected, the reaction of dicarboxylic acid VII with
1,3-dichloro-2-propanol was strictly stereoselective; as
a result, crown compound IX with cis,syn,cis-junction
of the polyester and cyclohexene rings was obtained.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

1062
Yields, boiling points, refractive indices, elemental analyses, and IR spectra of compounds V VII and IX XI
Found, % Calculated, %
SHABANOV et al.
Comp. Yield,
bp,
C
1
n2D0
Formula
IR spectrum (KBr), , cm
no.
%
(p, mm)
C
H
C
H
V
34.6
27.6
155 (2)
mp 31
162 (2)
61.08
6.28 C20H24O8
6.25 C20H24O8
61.22
61.22
6.12 1722 (C O); 1642 (C C);
1196, 1280, 1296 (C Oester)
6.12 1736 (C O); 1640, 1660
VI
1.4202 61.19
(C C); 1064, 1088, 1296
(C Oester
)
VII
IX
76.34
32.03
135 (2)
110 (1)
1.4632 59.08
1.4659 59.26
6.21 C18H22O8
5.93 C21H26O9
59.01
59.71
6.01 1702 (COOH), 1728 (C O),
1640 (C C)
6.16 3792, 3744, 3456 (OH); 1736
(C O); 1660, 1636 (C C);
1180, 1208, 1248, 1280
(C Oester
)
X
XI
11.2
26.2
125 (2)
163 (1.5) 1.4864 60.26
1.4778 60.23
6.43 C12H16O5
6.41 C24H32O10 60.0
60.0
6.66 1728 (C O), 1637 (C C)
6.66 1724 (C O), 1644 (C C)
cis,syn,cis-junction of the rings, respectively. The
isomeric products were separated by vacuum distilla-
tion in combination with column chromatography.
Their structure was established on the basis of the
IR spectra and chemical transformations, and the
molecular weight was determined by iodometric titra-
tion. The hydrolysis of macroheterocycles X and XI
gave cis-diacid III and diethylene glycol which were
identified by both chemical and spectral methods.
d = 10 mm) charged with aluminum oxide of activity
grade II (according to Brockman); a 1:2 (by volume)
chloroform hexane mixture was used as eluent.
[2+2]-Macrocyclization of cis-4-cyclohexene-1,2-
dicarboxylic acid (III) with 1,2-dibromoethane.
Diacid III, 8.5 g (0.05 mol), was dissolved in 150 ml
of 1-butanol, and the solution was neutralized with
5.6 g (0.1 mol) of powdered potassium hydroxide.
The released water was removed by azeotrope distilla-
tion, the solution was heated to the boiling point, and
9.4 g (0.05 mol) of 1,2-dibromoethane was added
with stirring over a period of 2 h. The mixture was
stirred for 20 h under reflux. When the reaction was
complete (TLC), the solvent was removed under
reduced pressure (25 mm), the residue was treated
with octane (5 50 ml), the extract was evaporated,
and the residue was distilled in a high vacuum. Two
fractions were thus obtained and were subjected to
to column chromatography on Al2O3 to isolate cis-
2,3 : 10,11-bis(1,2,3,6-tetrahydrobenzo)-1,4,9,12-tetra-
oxo-5,8,13,16-tetraoxa-syn-cyclohexadecane (V) and
cis-2,3 : 10,11-bis(1,2,3,6-tetrahydrobenzo)-1,4,9,12-
tetraoxo-5,8,13,16-tetraoxa-anti-cyclohexadecane (VI)
(see table).
Taking into account that compound XI shows in
the IR spectrum only one absorption band from the
1
double bonds ( C C 1644 cm ), cis,syn,cis-junction
of the cyclohexene and polyester rings therein may be
assumed.
EXPERIMENTAL
The IR spectra were recorded on Beckmann and
UR-20 spectrometers from samples pelleted with KBr.
The mass spectra (70 eV) of compounds V and VI
were recorded on an MKh-1310 spectrometer, batch
inlet temperature 235 C. The progress of reactions
and the purity of products were monitored by TLC on
Silufol plates. Mono- and dipotassium salts of cis-4-
cyclohexene-1,2-dicarboxylic acid were obtained by
potentiometric titration in 1-butanol using glass and
silver chloride electrodes; the pH was measured with
the aid of a pH-340 instrument. Standard solutions of
iodine (0.01 M) and sodium thiosulfate (0.005 M)
were used in the iodometric titration of compounds
V, VI, and IX XI. Stereoisomers V and VI were
separated by vacuum distillation followed by column
chromatography using a glass column (h = 100 mm,
1,2-Bis(2-carboxy-1,2,3,6-tetrahydrobenzoyloxy)-
ethane (VII) was synthesized in a similar way from
8.5 g (0.05 mol) of diacid III, 2.8 g (0.05 mol) of
powdered potassium hydroxide, and 4.7 g (0.025 mol)
of 1,2-dibromoethane. The properties of product VII
are given in table.
Following the above procedure, from 18.3 g
(0.05 mol) of compound VII and 9.4 g (0.05 mol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 7 2002

STEREOCHEMISTRY OF MACROCYCLIZATION OF cis-4-CYCLOHEXENE-.. .
1063
1,2-dibromoethane we obtained 34.6% of cis,syn,cis
isomer V.
cis-2,3 : 10,11-Bis(1,2,3,6-tetrahydrobenzo)-1-
hydroxy-1,4,9,12-tetraoxo-5,8,13,16-tetraoxa-syn-
cycloheptadecane (IX). Following the above proce-
dure, from 9.15 g (0.025 mol) of compound VII and
3.225 g (0.025 mol) of 1,3-dichloro-2-propanol we
obtained 32% of compound IX.
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Containing Functional Groups), Moscow: NIITEKhim,
1989.
2. Shabanov, A.L., Zh. Vses. Khim. Ob-va, 1991, vol. 26,
Macrocyclization of cis-4-cyclohexene-1,2-dicar-
boxylic acid (III) with 1,5-dichloro-3-oxapentane.
Following the above procedure, the reaction of 8.5 g
(0.05 mol) of diacid III, 5.6 g (0.1 mol) of powdered
KOH, and 7.16 g (0.05 mol) of 1,5-dichloro-3-oxa-
pentane gave cis-2,3-(1,2,3,6-tetrahydrobenzo)-1,4-
dioxo-5,8,11-trioxacycloundecane (X) and cis-
2,3 : 13,14-bis(1,2,3,6-tetrahydrobenzo)-1,4,12,15-
tetraoxo-5,8,11,16,19,22-hexaoxa-syn-cyclodocosane
(XI) (see table).
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