Dual mechanism of enamine-enamine rearrangement of 1,3-diaryl-3-(1-imidazolyl)propen-2-ones

Article abstract of DOI:10.1023/A:1016515710278

The formation of 1,3-diaryl-3-(1-imidazolyl)propen-1,3-diol that is an intermediate of enamine-enamine rearrangement of 1,3-diaryl-3-(1-imidazolyl)propen-1-ones constitutes the key stage of the dual mechanism of the rearrangement proper. The reaction of 1,3-diaryl-2,3-dibromopropan-1-ones with a primary amine provides 1,3-diaryl-3-iminopropan-1-ones as a result of enamine-imine prototropic rearrangement.

Full text of DOI:10.1023/A:1016515710278

Russian Journal of Organic Chemistry, Vol. 38, No. 4, 2002, pp. 593 594. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 4, 2002,
pp. 620 621.
Original Russian Text Copyright
2002 by M. Rekhter, B. Rekhter.
Dual Mechanism of Enamine enamine Rearrangement
of 1,3-diaryl-3-(1-imidazolyl)propen-2-ones
M. A. Rekhter and B. ARekhter
Institute of Biological Plant Protection, Moldavian Academy of Sciences, Kishinev, 2069 Moldova
Received April 4, 2001
Abstract The formation of 1,3-diaryl-3-(1-imidazolyl)propen-1,3-diol that is an intermediate of enamine
enamine rearrangement of 1,3-diaryl-3-(1-imidazolyl)propen-1-ones constitutes the key stage of the dual
mechanism of the rearrangement proper. The reaction of 1,3-diaryl-2,3-dibromopropan-1-ones with a
primary amine provides 1,3-diaryl-3-iminopropan-1-ones as a result of enamine imine prototropic re-
arrangement.
The condensation of , -dibromoketones with
secondary amines (1,2,4-triazole, imidazole, piperi-
dine, diethylamine, diethanolamine) in DMSO, DMF,
or dioxane is a general procedure for preparation of
aminochalcones [1 4]. The reaction is commonly
carried out at tenfold molar excess of amine to ensure
complete consumption of dibromoketone and to
provide a possibility of products isolation without use
of chromatography. At the condensation in excess of
liquid amine that serves also as solvent the latter is
easily recovered by distillation from the reaction mix-
ture. The hydrolysis of 1,3-diketones with piperidino
or diethylamino groups to carbonyl compounds and
secondary amines (in dilute acetate buffer and in
perchloric acid) [5], in future presumably with
overheated steam, is of special interest for prepara-
tion of monoheteryl- and diheteryl 1,3-diketones that
can find application as complexing agents in the
chemistry of radioactive elements, as is applied
thenoyltrifluoroacetone.
solutions in DMSO containing only compound I or
VI no changes were observed. The heating of these
solutions to 140 160 C for 20 min resulted in forma-
tion of a mixture of enamines I and VI with the latter
prevailing. Similar transformation was previously
observed without solvent. However at temperature
lowered to 120 125 C neither of the enamines suffers
isomerization.
The results of these experiments can be understood
in assumption that in the solution or in frozen DMSO
operates an alternative concerted rearrangement
mechanism. The rearrangement is catalyzed by a
complex of imidazolium ion VII with imidazole VIII
that effects a proton transfer from a nitrogen atom of
heterocycle to the oxygen atom of CO group. This
complex is indispensable not only for occurrence of
1,3-migration of the imidazole ring but also for trans-
formation of C=O group into a tertiary alcohol
group. Simultaneously the arising in the process
imidazolide anion IX effects deprotonation of inter-
mediate II. Because of high concentration of the
catalyst and of rearrangement mechanism inter-
mediate IV forms at high rate. This is evidenced by
formation of enamines I and VI mixture within
30 min at 20 C [3].
The reaction of 2,3-dibromo-1-(2,4-dichloro-
phenyl-3-(4-nitrophenyl)propan-1-one with imidazole
afforded a mixture of isomeric enamines I and VI [3].
Therewith compound I can be converted into com-
pound VI. In [3] a unique mechanism was proposed
for this enamine enamine rearrangement (I)
(VI)
The described condensation is carried out also with
the primary amines. For instance, reaction of 2,3-di-
bromo-1,3-diphenylpropan-1-one (X) with cyclohexyl-
amine (XI) in solution or in frozen DMSO apparently
gives rise to enamine XII as intermediate that
undergoes a prototropic rearrangement to afford
1,3-diphenyl-3-cyclohexyliminopropen-1-one (XIII)
(Scheme 2).
occurring at 20 C in DMSO and at 20 C in frozen
DMSO within 24 240 h or at 140 160 C without
solvent occurring within 20 min. The presumed
mechanism included intermediates III and IV
(Scheme 1).
When the reaction mixture is frozen in 30 seconds
after mixing the reagents and then is maintained at
39 40 C for 120 h the single product of condens-
ation is obtained, compound I. At 20 C within 4 h in
It follows from the above reasoning that in reaction
of chalcone dibromide with sodium imidazolide in
1070-4280/01/3804-593$27.00 2002 MAIK Nauka/Interperiodica

594
M. REKHTER, B. REKHTER
The temperature dependence of equilibrium ratio
Scheme 1.
of compounds I and VI was performed by means of
TLC on Silufol plates in the system benzene acetone,
2: 1 [Rf 0.73 (I), 0.62 (VI)]. Visual estimation of
components was based on intensity of spots; as refer-
ence were used solutions of both compounds of equal
concentration.
3-Piperidino-1,3-diphenylpropen-1-one. Under
conditions preventing access of CO2 were thoroughly
mixed 19.4 g (0.05 mol) of 2,3-dibromo-1,3-di-
phenylpropan-1-one (X) and 42.5 g (0.5 mol) of
piperidine. The mixture was either maintained at
20 C for 5 days or heated to 80 C for 16 h. The con-
sumption of dibromide X was monitored by TLC in
systems benzene and benzene acetone, 4: 1 (develop-
ment in iodine vapor). Piperidine was distilled off,
the residue was diluted with 150 ml of water, and the
reaction product was extracted into benzene (6
100 ml). Combined extracts were washed with water
(3 70 ml), dried on Na2SO4 and evaporated to
dryness. Yield 67%, mp 3 34 C (from a mixture
benzene hexane, 1: 1). Found, %: C 82.15; H 7.01;
N 5.13. C20H21NO. Calculated, %: C 82.43; H 7.26;
N 4.80.
1,3-Diphenyl-3-cyclohexylaminopropen-1-one
(XIII). A solution of 3.68 g (0.01 mol) of dibromide
X and 9.9 g (0.1 mol) of cyclohexylamine in 40 ml
of DMSO was stirred for 30 s, then was frozen and
either maintained for 120 h at 30 40 C or 72 h at
20 C. On dilution of the reaction mixture with water
(360 ml) the workup was done as above. Yield 60%,
mp 52 54 C (from a mixture benzene hexane, 2: 1).
Mass spectrum, m/z: 305 M+ , 200, 105.
Ar1
= = 4-O2NC6H4.
2,4-Cl2C6H3, Ar2
anhydrous DMSO the expected product would be
enamine I, and in aqueous DMSO where would
operate the catalytic system imidazolium cation VII
imidazole VIII, 1: 4, each isomer I or VI would be
converted in their equilibrium mixture whose com-
position depends on the temperature of the process.
REFERENCES
1. Rekhter, M.A., Grushetskaya, G.N., Panasenko, A.A.,
and Krimer, M.Z., Khim. Geterotsikl. Soed., 1993,
vol. 29, no. 2, pp. 266 267.
2. Rekhter, M.A., Grushetskaya, G.N., Panasenko, A.A.,
and Krimer, M.Z., Khim. Geterotsikl. Soed., 1995,
vol. 31, no. 7, pp. 910 914.
3. Rekhter, B.A. and Rekhter, M.A., Khim. Geterotsikl.
Soed., 1998, vol. 34, no. 4, pp. 561 563.
4. Makaev, F.Z., Gudima, A., Pogrebnoi, I.L., and
Rekhter, M.A., Abstracts of Papers, I Vserossiiskoi
konferentsii po geterotsiklam (1st All-Union Confer-
ence on Heterocycles), Suzdal,, 2000, p. 326.
5. Stamhuis, E.J., Enamines: Synthesis, Structure and
Reactions Cook, A.G., Ed., New York, 1969.
EXPERIMENTAL
Melting points were measured on Boetius device
and are reported uncorrected. Mass spectra were
registered on mass spectrometer MKh-1320 with
direct injection of sample into the ion source; ion
source temperature 60 C, ionizing electrons energy
70 eV, emission current 50 A. DMSO used in the
synthesis was commercial product of chemically
pure grade, cyclhexylamine and piperidine were
distilled just before use.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002