ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 491–493. © Pleiades Publishing, Ltd., 2012. Original Russian Text © Ya.S. Kayukov, S.V. Karpov, I.N. Bardasov, O.V. Ershov, M.Yu. Belikov, O.E. Nasakin, O.V. Kayukova, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4, pp. 493–495.
Reactions of Tetracyanocyclopropyl Ketones with Ammonia and Primary Amines Ya. S. Kayukova, S. V. Karpova, I. N. Bardasova, O. V. Ershova, M. Yu. Belikova, O. E. Nasakina, and O. V. Kayukovab a
I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia e-mail:
[email protected] b
Chuvash Agricultural Academy, Cheboksary, Russia Received November 3, 2011
Abstract—Reactions of aliphatic 2,2,3,3-tetracyanocyclopropyl ketones with aqueous ammonia afforded 4-alkyl-4-amino-2-oxo-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitriles with conservation of the three-membered ring. Reactions of the same compounds with primary amines were accompanied by opening of the cyclopropane ring, and they led to the formation of 5-amino-6,6a-dimethyl-2-oxo-1,2,6,6a-tetrahydropyrrolo[2,3-b]pyrrole-3,4-dicarbonitriles as a result of successive heterocyclizations.
DOI: 10.1134/S1070428012040045 The structure of compounds IIa–IId was determined by IR and 1 H NMR spectroscopy and mass spectrometry. Their IR spectra contained absorption bands typical of stretching vibrations of carbonyl group (1700–1719 cm–1), unconjugated cyano groups (2252–2257 cm–1), C–H bond at the cyclopropane ring (3062–3080 cm–1), and N–H bonds in the amino group and pyrrole ring (3190–3348 and 3429–3497 cm–1). In the 1H NMR spectra of IIa–IId signal from the pyrrole NH proton was observed at δ 8.82–9.29 ppm, protons in the amino group resonated at δ 7.06–7.54 ppm, the 5-H proton gave a signal at δ δ 4.87–5.21 ppm, and signals from alkyl substituents appeared in the region δ 0.92–1.81 ppm with appropriate multiplicity. A probable reaction scheme involves addition of ammonia at the carbonyl group with formation of intermediate A, and no opening of the cyclopropane ring occurs. Presumably, transformation off the carbonyl group into hemiaminal reduces the reactivity of
2,2,3,3-Tetracyanocyclopropyl ketones [1] react with nucleophilic reagents to give heterocyclic compounds with various structures and functional substituents. For example, their reactions with alcohols in the presence of the corresponding alkoxides lead to dihydrofuran derivatives [2–4], reactions with ketone oximes yield dihydrocyclopropa[c]pyrroles [2], sodium hydroxide gives rise to pyrrolo[3,4-c]pyridines [5], pyrrolo[3,4-c]pyridazine derivatives are formed in reactions with hydrazine hydrate [6], and cyclopropa[c]pyrrolidines result from reactions with ammonia [7]. In continuation of our studies in this field, in the present work we examined reactions of aliphatic tetracyanocyclopropyl ketones with ammonia and primary amines. 3-Acylcyclopropane-1,1,2,2-tetracarbonitriles Ia–Id reacted with aqueous ammonia to produce 69– 87% of 4-alkyl-4-amino-2-oxo-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitriles IIa–IId in which the three-membered ring was conserved (Scheme 1).
Scheme 1. OH
O CN
R
CN H
CN CN Ia–Id
NH3
R
NH HN
R
CN
H 2N
CN
H 2N CN
H
O
O
CN
CN
H
CN A
CN B
R = Me (a), Et (b), Pr (c), t-Bu (d).
491
R
CN
H 2N H
CN CN
IIa–IId
KAYUKOV et al.
492
Scheme 2. O
O CN
R
CN H
R' NH2
CN
NC
CN Ia, Id
R' NH2
CN R' NH3
R
CN
R'
NC
CN
NC CN
R
CN
CN
NH OH CN
H N R'
CN C
CN
D
CN
NC
CN
CN
NC
HN
H N R'
NC
NH
O
R
R
N H
O N
O R'
R
H 2N
N H
O N R'
E
R
N H
IIIa–IIIc
III, R = R′ = Me (a); R = t-Bu, R′ = Me (b); R = Me, R′ = i-Pr (c).
the CH proton in the cyclopropane ring. The subsequent interaction between the hydroxy group and the nearest cyano group leads to closure of furan ring with formation of intermediate B which undergoes iminolactone–lactam rearrangement to final product II. Reactions of compounds Ia and Id with primary amines were accompanied by opening of the threemembered ring. The reason is that primary amines are stronger bases than ammonia. Depending on the nature of the alkyl radical in the initial cyclopropyl ketone and amine, the reaction may stop at the stage of formation of alkylammonium 2-acyl-1,1,3,3-tetracyanopropenide or go further to give finally the corresponding 6,6a-dialkyl-5-amino-2-oxo-1,2,6,6a-tetrahydropyrrolo[2,3-b]pyrrole-3,4-dicarbonitriles IIIa– IIIc in 71–84% yield (Scheme 2). The formation of structure III was supported by the IR and 1H NMR data. Compounds IIIa–IIIc displayed in the 1H NMR spectra signals from the corresponding alkyl groups, a singlet from the NH proton at δ 7.15– 8.20 ppm, and signals from the NH2 group at δ 8.38– 9.23 ppm as two broadened singlets. IR absorption bands in the regions 2193–2222, 3169–3322, and 1683–1698 cm–1, indicated the presence of conjugated cyano groups, amino group, and C=C bond, respectively; absorption bands at 3422–3440 cm –1 can also be assigned to stretching vibrations of NH or NH2 group. Presumably, the first step of the process is proton abstraction from the cyclopropane ring by the action of amine, which is followed by ring opening. Amine molecule then adds at the carbonyl group to give amino alcohol C which undergoes intramolecular cyclization involving the hydroxy group and the nearest cyano group. Iminofuran intermediate D thus formed is
converted into pyrrolidinone intermediate E, and next follows intramolecular addition of the alkylamino group at the second cyano group with formation of pyrrolo[2,3-b]pyrrole system III (Scheme 2). EXPERIMENTAL The progress of reactions and the purity of products were monitored by TLC on Silufol UV-254 plates; spots were detected by UV irradiation, treatment with iodine vapor, or heating. The IR spectra were recorded in mineral oil on an FSM 1201 spectrometer. The 1 H NMR spectra were measured from solutions in DMS O - d 6 o n a B r u k e r A M - 5 0 0 s p e c t r o me t e r (500.13 MHz) using tetramethylsilane as internal reference. The mass spectra (electron impact, 70 eV) were obtained on a Finnigan MAT INCOS-50 instrument. 4-Amino-4-methyl-2-oxo-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitrile (IIa). Compound Ia, 2.46 g (0.01 mol), was dissolved under stirring in 10 ml of 25% aqueous ammonia. The solution was left to stand for 12 h, and the precipitate was filtered off, washed with water, and dried in a vacuum desiccator over P 2 O 5 . Yield 1.39 g (69%), mp 137–138°C. IR spectrum, ν, cm–1: 3429 (NH); 3345, 3211 (NH2); 3062 (C–H); 2257 (C≡N); 1719 (C=O). 1H NMR spectrum, δ, ppm: 1.52 s (3H, CH3), 4.87 s (1H, 5-H), 7.06 s (2H, NH2), 8.89 s (1H, NH). Mass spectrum, m/z (Irel, %): 201 (22), 143 (47), 115 (12). Found, %: C 53.60; H 3.60; N 34.89. C9H7N5O. Calculated, %: C 53.73; H 3.51; N 34.81. M 201.18. Compounds IIb–IId were synthesized in a similar way. 4-Amino-4-ethyl-2-oxo-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitrile (IIb). Yield 81%, mp 132–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 4 2012
REACTIONS OF TETRACYANOCYCLOPROPYL KETONES
133°C. IR spectrum, ν, cm–1: 3504 (NH); 3351, 3207 (NH 2 ); 3075 (C–H); 2252 (C≡N); 1703 (C=O). 1 H NMR spectrum, δ, ppm: 0.92 t (3H, CH 3 , 3 J = 7.5 Hz), 1.81 q (2H, CH2, 3J = 7.5 Hz), 4.89 s (1H, CH), 7.10 s (2H, NH2), 8.85 s (1H, NH). Mass spectrum, m/z (Irel, %): 215 (17), 171 (57), 132 (76), 56 (100). Found, %: C 55.19; H 4.34; N 32.91. C10H9N5O. Calculated, %: C 55.81; H 4.22; N 32.54. M 215.08. 4-Amino-2-oxo-4-propyl-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitrile (IIc). Yield 81%, mp 126– 127°C. IR spectrum, ν, cm–1: 3488 (NH); 3353, 3212 (NH 2 ); 3080 (C–H); 2250 (C≡N); 1703 (C=O). 1 H NMR spectrum, δ, ppm: 0.91 t (3H, CH 3 , 3 J = 7.3 Hz), 1.33–1.42 m (2H, CH2), 1.74–1.78 m (2H, CH2), 4.97 s (1H, CH), 7.09 s (2H, NH2), 8.86 s (1H, NH). Mass spectrum, m/z (Irel, %): 229 (7), 159 (75), 158 (74), 70 (45), 43 (100). Found, %: C 57.84; H 4.91; N 30.47. C11H11N5O. Calculated, %: C 57.63; H 4.84; N 30.55. M 229.24. 4-Amino-4-tert-butyl-2-oxo-3-azabicyclo[3.1.0]hexane-1,6,6-tricarbonitrile (IId). Yield 85%, mp 165–166°C. IR spectrum, ν, cm –1 : 3497 (NH); 3348, 3207 (NH2); 3080 (C–H); 2252 (C≡N); 1700 (C=O). 1H NMR spectrum, δ, ppm: 0.93 s (9H, t-Bu), 5.21 s (1H, CH), 7.14 s (2H, NH2), 8.82 s (1H, NH). Mass spectrum, m/z (Irel, %): 186 (5) [M – 57]+, 57 (100). Found, %: C 59.19; H 5.44; N 28.91. C12H13N5O. Calculated, %: C 59.25; H 5.39; N 28.79. M 243.26. 5-Amino-6,6a-dimethyl-2-oxo-1,2,6,6a-tetrahydropyrrolo[2,3-b]pyrrole-3,4-dicarbonitrile (IIIa). Compound Ia, 1.88 g (0.01 mol), was dissolved in 10 ml of acetonitrile, 1.86 g of 33% aqueous methylamine was added under stirring, the mixture was stirred for 10 min, and the precipitate was filtered off and washed with water. Yield 1.72 g (80%), mp 164– 165°C. IR spectrum, ν, cm–1: 3423 (OH); 3201, 3308 (NH2); 2200, 2222 (C≡N); 1683 (C=C). 1H NMR spectrum, δ, ppm: 1.50 s (3H, CH3), 2.86 s (3H, NCH3), 7.15 s (1H, NH), 8.51 s and 8.60 s (2H, NH2). Mass spectrum, m/z (Irel, %): 215 (15), 200 (40). Found, %: C 55.80; H 4.11; N 32.63. C10H9N5O. Calculated, %: C 55.81; H 4.22; N 32.54. M 215.21. 5-Amino-6a-tert-butyl-6-methyl-2-oxo-1,2,6,6atetrahydropyrrolo[2,3-b]pyrrole-3,4-dicarbonitrile (IIIb). Compound Id, 2.26 g (0.01 mol), was dissolved in 10 ml of acetonitrile, 1.86 g of 33% aqueous methylamine was added under stirring, the mixture was stirred until the reaction was complete (TLC) and evaporated, the residue (an oily substance) was ground
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with cold water, and the precipitate was filtered off and washed with water. Yield 2.16 g (84%), mp 240– 241°C. IR spectrum, ν, cm–1: 3440 (OH); 3322, 3208 (NH 2 ); 2205, 2193 (C≡N); 1690 (C=C). 1 H NMR spectrum, δ, ppm: 0.93 (9H, t-Bu), 2.92 s (3H, NCH3), 8.20 s (1H, NH), 8.40 s and 8.74 s (2H, NH2). Mass spectrum, m/z (Irel, %): 257 (4), 200 (24), 57 (100). Found, %: C 60.53; H 5.97; N 27.12. C13H15N5O. Calculated, %: C 60.69; H 5.88; N 27.22. M 257.29. 5-Amino-6-isopropyl-6a-methyl-2-oxo-1,2,6,6atetrahydropyrrolo[2,3-b]pyrrole-3,4-dicarbonitrile (IIIc). Compound Ia, 1.88 g (0.01 mol), was dissolved in 10 ml of acetonitrile, 1.18 g (0.02 mol) of isopropylamine was added under stirring, the mixture was stirred until the reaction was complete (TLC) and evaporated, the residue (an oily substance) was ground with cold water, and the precipitate was filtered off and washed with water. Yield 1.82 g (75%), mp 220– 221°C. IR spectrum, ν, cm–1: 3417 (OH); 3312, 3169 (NH2); 2221, 2204 (C≡N); 1698 (C=C). 1H NMR spectrum, δ, ppm: 1.25 d [3H, CH(CH 3 ) 2 , 3 J = 6.9 Hz], 1.32 d [3H, CH(CH3)2, 3J = 6.8 Hz], 1.64 s (3H, CH3), 3.97 quint (3H, NCH, 3J = 6.9 Hz), 7.80 s (1H, NH), 8.38 s and 8.72 s (2H, NH 2 ). Mass spectrum, m/z (Irel, %): 243 (16), 228 (57), 200 (44), 185 (15), 173 (30), 158 (90). Found, %: C 59.21; H 5.46; N 28.70. C12H13N5O. Calculated, %: C 59.25; H 5.39; N 28.79. M 243.26. REFERENCES 1. Bardasov, I.N., Kayukova, O.V., Kayukov, Ya.S., Ershov, O.V., and Nasakin, O.E., Zh. Prikl. Khim., 2009, vol. 82, p. 1332. 2. Bardasov, I.N., Kayukova, O.V., Kayukov, Ya.S., Ershov, O.V., Nasakin, O.E., and Tafeenko, V.A., Russ. J. Org. Chem., 2009, vol. 45, p. 1325. 3. Bardasov, I.N., Kayukova, O.V., Kayukov, Ya.S., Ershov, O.V., Nasakin, O.E., and Belikov, M.Yu., Russ. J. Org. Chem., 2007, vol. 43, 1565. 4. Bardasov, I.N., Kayukova, O.V., Kayukov, Ya.S., Ershov, O.V., Belikov, M.Yu., and Nasakin, O.E., Khim. Geterotsikl. Soedin., 2009, vol. 45, p. 1297. 5. Bardasov, I.N., Kayukova, O.V., Kayukov, Ya.S., Ershov, O.V., Nasakin, O.E., and Tafeenko, V.A., Russ. J. Org. Chem., 2010, vol. 46, p. 1266. 6. Kayukov, Ya.S., Bardasov, I.N., Kayukova, O.V., Ershov, O.V., Nasakin, O.E., Eremkin, A.V., and Tafeenko, V.A., Russ. J. Org. Chem., 2011, vol. 47, p. 722. 7. Sheverdov, V.P., Ershov, O.V., Nasakin, O.E., Selunina, E.V., Tikhonova, I.G., and Khrustalev, V.N., Mendeleev Commun., 2000, no. 1, p. 25.
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