Reaction of crystals of 5-benzylidenerhodanine and its diethylammonium salt with diazomethane

Article abstract of DOI:10.1023/A:1013967407158

The reaction of crystalline desmotropic forms of 5-benzylidenerhodanine and its diethylammoium salt and crystal solvates with gaseous diazomethane was studied. Hydrogen bonds do not shield the reaction centers of the ambident triad and exert no effect on

Full text of DOI:10.1023/A:1013967407158

Russian Journal of General Chemistry, Vol. 71, No. 10, 2001, pp. 1605 1607. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 10, 2001,
pp. 1693 1695.
Original Russian Text Copyright
2001 by Aronova, Ginak.
Reaction of Crystals of 5-Benzylidenerhodanine
and Its Diethylammonium Salt with Diazomethane
E. B. Aronova and A. I. Ginak
St. Petersburg State Institute of Technology, St. Petersburg, Russia
Received September 28, 2000
Abstract The reaction of crystalline desmotropic forms of 5-benzylidenerhodanine and its diethyl-
ammoium salt and crystal solvates with gaseous diazomethane was studied. Hydrogen bonds do not shield the
reaction centers of the ambident triad and exert no effect on their reactivity.
Investigations into the properties of solid organic
compounds are of scientific importance. Such investi-
gations are performed by various theoretical and
instrumental methods (X-ray diffractometry, UV,
NMR, and IR spectroscopy, gas-phase electron dif-
fraction, chromatography), including chemical. The
latter arroaches are of particular interest, since by
examining the composition and structure of reaction
products one can obtain the most complete informa-
proposal has been confirmed by the observation that
pure desmotropic forms react with diazomethane to
give exclusively monomethylation products. At the
same time, it is known that potentially tautomeric
compounds on crystallization show tendency for intra-
and intermolecular hydrogen bonding to form centro-
symmetrical dimers, as well as 3D structures: chains
[5], helices [6], nets [7], etc., and this may essentially
affect both the reactivity of such compounds and
tion about the site and character of reaction centers, product ratio. For instance, if both tautomeric forms
transmission of electronic effects of substituents on
the reaction centers, stability of reaction products, as
well as establish relationships between these para-
meters and practical properties of compounds, such as
biological activity, electronic effects, etc. Chemical
methods of investigation of organic crystals include
nucleophilic substitution and addition reactions. Thus,
solid-phase alkylation and acylation reactions have
been used to determine the geometry of reaction
centers in ambifunctional compounds [1, 2], which
allowed some theoretical conceprts of the geometry
and reactivity of the ambident triad to be developed
and a number of previously unknown biologically
active compounds to be obtained.
are close in energy, the hydrogen atom may oscillate
along the hydrogen-bond axis, and both tautomets
may be in dynamic equilibrium, i.e. fast tautomeric
interconversions may occur [8]. As a result, most
likely, an isomeric mixture will form on diazomethane
methylation.
According to spectral and X-ray diffraction data,
crystalline thiazolidin-4-ones exist both as monomers
and as self-associates with various configuration of
hydrogen bonds, including dimers [9 12], and when
crystallized from organic solvents, these compounds
form stoichiometric solvate complexes. For instance,
crystallization of 5-benzylidenerhodanine from di-
methylformamide gives rise to coarse transparent
crystals, where, according to X-ray diffraction data
Proceeding with reactivity studies on solid-phase
reactions of ambident compounds, we performed re-
actions of crystalline desmotropic forms of 5-benzyl-
idenerhodanine and its quaternary ammounium salts
prepared by various methods with gaseous diazo-
methane. It is known [3] that crystalline rhodanine
and its 5-benzylidene derivatives exhibit dual reac-
tivity toward gaseous diazomethane, which results in
both N and S methylation of the ambident triad. It has
been proposed [4] that the reaction products are
formed via direct methylation of the desmotropic
form, i.e. by the protonated site of the ambident triad,
rather then via rearrangement of the methyldiazonium
cation ion-paired with the ambident triad. This
[11],
each
5-benzylidene-2-thiothiazolidin-4-one
molecule is hydrogen-bonded with one solvent
molecule.
O=C N H
Ph CH=C C=S
O
CH N(CH3)2
S
2
Crystal solvates of 5-benzylidene-2-mercapto-
-
thiazolin-4-one, an isomer of 5-benzylidenerhodanine,
were not found, even though we previously establi-
shed [12] that 5-benzylidenerhodanine crystallizes as a
tautomaric mixture. The thione form, 5-benzylidene-
rhodanine, forms cubic crystals, while the thiol form,
1070-3632/01/7110-1605$25.00 2001 MAIK Nauka/Interperiodica

1606
ARONOVA, GINAK
5-benzylidene-2-mercapto- 2-tiazolin-4-one, thread-
like crystals. Both forms are readily visible in a
microscope and readily separable. Therefore, 5-benzyl-
idenerhodanine is the most interesting object for
studying the effect of hydrogen bonds on the reacti-
vity of organic crystals of ambifunctional compounds.
crystallization; the purity of the product was checked
by chromatography [14]. The preparation and purifica-
tion of 2- and 3-methyl-5-benzylidenerhodanines used
as references in TLC analysis we described earlier
[15].
Gaseous diazomethane was synthesized by treat-
ment of N-nitrosomethylurea with 40% potassium
hydroxide [16] and purified by passing over KOH
granules.
To assess the effect of solvent nature on the crystal
structure of 5-benzylidenerhodanine and the reactivity
of its nucleophilic centers, we crystallized this sub-
strate from various solvents (benzene, toluene, diethyl
ether, ethyl acetate, tetrahydrofuran, acetonitrile,
dimethylformamide, methanol, ethanol, propanol, and
70% aqueous acetone, ethanol, and dimethylform-
amide) and obtained pure crystals with a stable melt-
ing point 206 C and a crystal solvate of 5-benzyl-
idenerhodanine and dimethylformamide, and treated
the resulting crystals with diazometane. It was found
that the ratio of the 3-methyl-5-benzylidenerhodanine
Diethylammonium 5-benzylidenerhodanine. Di-
ethylamine, 0.01 mol, was added to 2.21 g of 5-
benzylidenerhodanine in 30 ml of chlorform. The
mixture was stirred for 10 min, and the solvent was
removed in a vacuum. Yield 98%, mp 158 C. Found,
%: C 57.2; H 6.0; N 9.6; O 5.7; S 21.7. C14H17N2OS2.
Calculated, %: C 57.1; H 6.1; N 9.5; O 5.6; S 21.8.
Reaction of diethylammonium 5-benzylidene-
rhodanine with diazomethane in the solid phase.
Gaseous diazomethane was passed through 5
and
2-methylthio- 2-5-benzylidenethiazolin-4-one
isomers is always, regardless of the solvent for crys-
tallization, 1.47 0.01. With the crystal solvate, the
same isomeric ratio was obtained, implying that sub-
strate solvent hydrogen bonds here do not shield the
reaction centers and have no affect their reactivity.
4
10 mol of diethylammonium 5-benzylidenerhoda-
nine placed in a glass tube until compete conversion
of the starting compound. The reaction progress was
followed by TLC. The reaction product, 3-methyl-5-
benzylidenerhodanine, was washed with water to
remove diethylamine, dried, and identified by the Rf
value (two-dimensional TLC) and by the melting
point of the mixed sample with the 3-methyl-5-ben-
zylidenerhodanine obtained by the procedure in [13].
The constancy of the ratio of methylated isomers
(N/S) and its stability suggest accessibility for the
reagent of the NH and SH centers of the ambident
triad.
To evaluate the probability of the possible shield-
ing of the reaction centers of the ambident triad by
other participants of the hydrogen bond, we performed
methylation with diazomethane of ammonium salts of
5-benzylidenerhodanine and the isomeric mixtures
obtained by treatment of the crystalline salts with
hydrogen chloride vapors. To this end, the crystalline
diethylammonium 5-benzylidenerhodanine isolated
from chloroform was treated with gaseous diazo-
methane. By TLC we detected in the reaction mixture
the N-methyl isomer only. Treatment of the former
salt with hydrogen chloride vapors gave a substrate
whose reaction with gaseous diazomethane resulted
in exclusive formation of the N CH3 isomer. The
S CH3 isomer was not detected on the chromatogram
Reaction of diethylammonium 5-benzylidene-
rhodanine with gaseous hydrogen chloride. Dry
gaseous hydrogen chloride [16] was passed through
4
5 10
mol of diethylammonium 5-benzylidene-
rhodanine placed in a glass tube until the starting
compound disappeared completely. The resulting
5-benzylidenerhodanine without isolation was treated
by gaseous diazomethane as described above to obtain
3-methyl-5-benzylidenerhodanine exclusively. The
product was identified as described above.
REFERENCES
1. Ginak, A.I., V’yunov, K.A., and Sochilin, E.G., Zh.
Org. Khim., 1970, vol. 6, no. 8, p. 1774.
even in trace amounts (the sensitivity of the method
10
2. Ramsh, S.M., Basova, Yu.G., Ginak, A.I., and So-
chilin, E.G., Zh. Org. Khim., 1981, vol. 17, no. 5,
p. 986.
was 10
M).
A conclusion thus can be drawn that hydrogen
bonds between the desmotropic forms of 5-benzyl-
idenerhodanine in solid and in crystal solvate exert
no effect on the reactivity of the thiamide triad.
3. Ginak, A.I. and Sochilin, E.G., Zh. Org. Khim., 1978,
vol. 14, no. 5, p. 1065.
4. Will, G., Nature, 1963, vol. 198, no. 4880, p. 575.
EXPERIMENTAL
5. Starova, T.L., Frank-Kamenetskaya, O.V., and
Usov, O.A., Zh. Strukt. Khim., 1982, vol. 23, no. 2,
p. 171.
The starting 5-benzylidenerhodanine was obtained
by the procedure in [13] and purified by triple re-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 10 2001

REACTION OF CRYSTALS OF 5-BENZYLIDENERHODANINE
1607
6. Starova, T.L., Frank-Kamenetskaya, O.V., and Ma-
karenskii, V.V., Kristallografiya, 1980, vol. 25, no. 8,
p. 1292.
(Chemistry of Organic Crystals), St. Petersburg:
Khimiya, 1994, p. 34.
12. Smorygo, N.A., V’yunov, K.A., Ginak, A.I., and So-
chilin, E.G., Abstracts of Papers, Konferentsiya FIMIK
(FIMIK Conf.), Kazan, 1971, p. 301.
7. Kondrashov, Yu.D., Kristallografiya, 1968, vol. 13,
no. 4, p. 622.
13. Brown, F.C., Chem. Rev., 1961, vol. 61, no. 5, p. 508.
8. V’yunov, K.A., Ginak, A.I., and Sochilin, E.G., Zh.
Prikl. Spektrosk., 1976, vol. 15, vol. 2, p. 866.
14. Ginak, A.I., V’yunov, E.G., and Sochilin, E.G., Zh.
Prikl. Khim., 1971, vol. 44, no. 9, p. 2123.
9. V’yunov, K.A., Ginak, A.I., and Sochilin, E.G., Zh.
Prikl. Spektrosk., 1977, vol. 27, no. 6, p. 1071.
15. Ginak, A.I. and Sochilin, E.G., Zh. Org. Khim., 1967,
vol. 3, no. 9, p. 1711.
10. van der Helm, D., Lessor, E.A., and Morrit, L.L.,
16. Obshchii praktikum po organicheskoi khimii (Basic
Manual on Organic Chemistry), Kost, A.N., Ed.,
Moscow: Mir, 1965, p. 532.
Acta Crystallogr., 1962, vol. 15, p. 1227.
11. Dymshits, V.A., Khimiya organicheskikh kristallov
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 10 2001