New transformation of α-acetylenic ketones under the action of 1,2-diaminoethane

Article abstract of DOI:10.1007/s11172-011-0030-1

A reaction of 3-aryl-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ones with 1,2-diaminoethane in boiling dioxane leads to 2-aryl-4,5-dihydro-1H-imidazoles and 1-(3,4,5-trimethoxy-phenyl)ethanone.

Full text of DOI:10.1007/s11172-011-0030-1

Russian Chemical Bulletin, International Edition, Vol. 60, No. 1, pp. 188—190, January, 2011
188
New transformation of αꢀacetylеnic ketones
under the action of 1,2ꢀdiaminoethane
M. P. Davydova,a S. F. Vasilevskii,a and G. A. Tolstikovb
aInstitute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 7350. Eꢀmail: vasilev@kinetics.nsc.ru
bN. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation
A reaction of 3ꢀarylꢀ1ꢀ(3,4,5ꢀtrimethoxyphenyl)propꢀ2ꢀynꢀ1ꢀones with 1,2ꢀdiaminoethane
in boiling dioxane leads to 2ꢀarylꢀ4,5ꢀdihydroꢀ1Hꢀimidazoles and 1ꢀ(3,4,5ꢀtrimethoxyꢀ
phenyl)ethanone.
Key words: αꢀacetylеnic ketones, heterocyclization, 1,2ꢀdiaminoethane, imidazolidines.
Earlier,1 we have reported the data on the reaction of
and 1,2ꢀdiaminoethane in dioxane (0.5 h) leads not only
to the expected 3ꢀ(2ꢀaminoethylamino)ꢀ3ꢀ(4ꢀnitroꢀ
phenyl)ꢀ1ꢀ(3,4,5ꢀtrimethoxyphenyl)propꢀ2ꢀеnꢀ1ꢀone (2)
(13%), but also to unexpected products of fragmentation
at the triple bond, i.e., 1ꢀ(3,4,5ꢀtrimethoxyphenyl)ethanꢀ
one (3) (35%) and 2ꢀ(4ꢀnitrophenyl)ꢀ4,5ꢀdihydroꢀ1Hꢀ
imidazole (4) (34%) (Scheme 1).
To find whether this reaction takes place in the case of
substrates having no additional electronꢀwithdrawing subꢀ
stituent (NO2), we carried out the reaction of 1,2ꢀdiamiꢀ
αꢀacetylеnic ketone 1 with amino compounds (hydrazine
hydrate, guanidine, hydroxylamine), which leads to hetꢀ
erocyclic derivatives, analogs of combretastatin Aꢀ4 (see
Ref. 2). In continuation of our study of nucleophilic addiꢀ
tion at the triple bond having in mind new analogs with
a heterocyclic bridge, we studied a reaction of αꢀalkynylꢀ
ketones with 1,2ꢀdiaminoethane.
Herein we have found that reflux of 3ꢀ(4ꢀnitrophenyl)ꢀ
1ꢀ(3,4,5ꢀtrimethoxyphenyl)propꢀ2ꢀynꢀ1ꢀone
(1)
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 180—181, January, 2011.
1066ꢀ5285/11/6001ꢀ188 © 2011 Springer Science+Business Media, Inc.

Cleavage of ynones
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
189
Scheme 2
H(5)Ph, J = 8.6 Hz); 11.13 (s, 1 H, NH). 13C NMR, δ: 45.25
(CH2NH2); 56.12 (2 OCH3); 60.83 (OCH3); 67.84 (CH2NH);
94.03 (CH); 104.34 (C(2´), C(6´)); 124.02 (C(3), C(5)); 128.87
(C(2), C(6)); 134.40 (C(1´)); 140.85 (C(1)); 141.26 (C(4´));
148.33 (C(4)); 153.03 (C(3´), C(5´)); 163.67 (CNH); 188.06 (CO).
IR (KBr), ν/cm–1: 3429 (NH). HRMS, found: m/z 384.1313
[M – NH3]+ (C20H20O6N2), 357.1084 [M – CH3CH=NH2]+
(C18H17O6N2). Calculated: M = 401.1581 (C20H23N3O6).
The reaction also yielded 1ꢀ(3,4,5ꢀtrimethoxyphenyl)ethanꢀ
one (3) (0.15 g, 35%), m.p. 76—78 °C (benzene) (cf. Ref. 3: m.p.
77—79 °C) and 2ꢀ(4ꢀnitrophenyl)ꢀ4,5ꢀdihydroꢀ1Hꢀimidazole (4)
(0.13 g, 34%), m.p. 242—244 °C (dioxane) (cf. Ref. 4: m.p.
242—243 °C).
noethane with phenylethynyl ketone 5 (Scheme 2). Howꢀ
ever, in this case formation of fragmentation products,
ketone 3 and imidazole 7, also took place, whose yields
were 45 and 42%, respectively. In addition, instead of
monosubstituted 1,2ꢀdiaminoethane, similar to compound
2, a product of the double addition, symmetric diamine 6,
was formed (6%).
In conclusion, an unusually ready cleavage at the actiꢀ
vated triple bond under the action of 1,2ꢀdiaminoethane
was found, which leads to the corresponding aryl methyl
ketones and 2ꢀarylꢀ4,5ꢀdihydroꢀ1Hꢀimidazoles.
The reaction of 1ꢀ(3,4,5ꢀtrimethoxyphenyl)ꢀ3ꢀphenylpropꢀ
2ꢀynꢀ1ꢀone (5)5 with 1,2ꢀdiaminoethane was carried out simiꢀ
larly, the reaction time was 9 h. The reaction mixture was conꢀ
centrated in vacuo, the residue was subjected to chromatography
on silica gel (eluent hexane, hexane—toluene (1 : 1), toluene,
toluene—AcOEt (1 : 1), AcOEt).
N,N´ꢀBis[3ꢀoxoꢀ1ꢀphenylꢀ3ꢀ(3,4,5ꢀtrimethoxyphenyl)propꢀ
1ꢀеnꢀ1ꢀyl]ethaneꢀ1,2ꢀdiamine (6). The yield was 0.07 g (6%),
m.p. 202—204 °C (benzene). 1H NMR (CDCl3), δ: 3.33 (m, 2 H,
CH2); 3.88 (s, 9 H, OMe); 5.68 (s, 1 H, =CH); 7.12 (s, 2 H,
H(2´), H(6´)); 7.26 (m, 2 H, H(2)Ph, H(6)Ph); 7.44 (m, 3 H,
H(3)Ph—H(5)Ph); 11.26 (s, 1 H, NH). 13C NMR, δ: 44.97 (CH2);
56.10 (2 OCH3); 60.78 (OCH3); 93.82 (CH); 104.22 (C(2´),
C(6´)); 127.51 (C(2), C(6)); 128.63 (C(3´), C(5´)); 129.41 (C(4));
134.99 (C(1´)); 135.35 (C(1)); 140.54 (C(4´)); 152.81 (C(3´),
C(5´)); 166.48 (CNH); 187.67 (CO). IR (KBr), ν/cm–1: 3437
(NH). Found (%): C, 69.94; H, 6.17; N, 4.35. C38H40N2O8.
Calculated (%): C, 69.96; H, 6.18; N, 4.29.
Experimental
IR spectra were recorded on a Bruker Vector 22 spectromeꢀ
ter in KBr pellets. NMR spectra were recorded on a Bruker AV
400 spectrometer (400.13 MHz) in CDCl3 or DMSOꢀd6. Mass
spectra were obtained on a Thermo Scientific DFS instrument
(Double Focusing Sector Mass Spectrometer, Thermo Electron
Corporation) with the direct inlet of the sample (the temperꢀ
ature of the ionization chamber was 220—270 °C, the
ionization potential was 70 eV). Merck 60 (0.063—0.2 mm) silica
gel was used for chromatography, TLC monitoring was perꢀ
formed on Silufol 60 F254 plates.
Reaction of 3ꢀ(4ꢀnitrophenyl)ꢀ1ꢀ(3,4,5ꢀtrimethoxyphenyl)ꢀ
propꢀ2ꢀynꢀ1ꢀone (1) with 1,2ꢀdiaminoethane. A mixture of keꢀ
tone 1 (see Ref. 1) (0.682 g, 2 mmol) and 1,2ꢀdiaminoethane
(0.12 g, 2 mmol) in dioxane (10 mL) was refluxed for 0.5 h.
The reaction progress was monitored by TLC (Silufol, AcOEt).
The reaction mixture was concentrated in vacuo, the residue
was subjected to chromatography on silica gel (eluent: hexꢀ
ane, hexane—toluene (1 : 1), toluene, toluene—AcOEt (1 : 1),
AcOEt).
The reaction also yielded 1ꢀ(3,4,5ꢀtrimethoxyphenyl)ethanꢀ
one (3) (0.35 g, 45%), m.p. 76—78 °C (benzene) (cf. Ref. 3: m.p.
77—79 °C) and 2ꢀphenylꢀ4,5ꢀdihydroꢀ1Hꢀimidazole (7) (0.21 g,
42%), m.p. 93—95 °C (benzene) (cf. Ref. 6: m.p. 92—94 °C).
3ꢀ(2ꢀAminoethylamino)ꢀ3ꢀ(4ꢀnitrophenyl)ꢀ1ꢀ(3,4,5ꢀtrimethꢀ
oxyphenyl)propꢀ2ꢀеnꢀ1ꢀone (2). The yield was 0.11 g (13%),
m.p. 258—260 °C (dioxane). H NMR (CDCl3), δ: 1.60 (br.s,
2 H, NH2); 3.34 (m, 2 H, C(1)H2); 3.76 (m, 2 H, C(2)H2); 3.93
(s, 9 H, OMe); 5.73 (s, 1 H, =CH); 7.15 (s, 2 H, H(2´), H(6´));
This work was financially supported by the Siberian
Branch of the Russian Academy of Sciences (Interdisciꢀ
plinary Grant 93), the Russian Foundation for Basic Reꢀ
search (Project No. 10ꢀ03ꢀ00257ꢀa), the Russian Acadeꢀ
my of Sciences (Grant 5.9.3), and the Chemistry Service
1
7.53 (d, 2 H, H(2)Ph, H(6)Ph, J = 8.6 Hz); 8.29 (d, 2 H, H(3)Ph
,

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 1, January, 2011
Davydova et al.
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in revised form October 19, 2010