3-Nitro-and 3-bromo-3-nitroacrylates in reactions with 2-phenyl-1,3-indanedione
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ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 8, pp. 1242-1243. ó Pleiades Publishing, Inc. 2006.
Original Russian Text ó A.S. Smirnov, S.V.Makarenko, V.M. Berestovitskaya, A.I. Pekki, K.S.Konovalenko, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 8, pp. 1259-1260.
1242
3-Nitro- and 3-Bromo-3-nitroacrylates in Reactions
with 2-Phenyl-1,3-indanedione
A.S. Smirnov, S.V . Makarenko, V .M. Berestovitskaya, A.I. Pekki, and K.S. Konovalenko
Herzen Russian State Pedagogical University, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
Received January 18, 2006
DOI: 10.1134/S1070428006080264
Alkyl 3-nitroacrylates are highly reactive reagents used in the designed synthesis of practically important substances. In particular methods were developed based on these compounds for preparation of oryzoxymycin antibiotic [1], and also for b -amino acids used in the synthesis of b -peptides [2, 3]. An introduction of a halogen into the molecules of alkyl 3-nitroacrylates a priori extends their synthetic opportunities [4, 5] and makes it possible to regard the halonitroacrylates as promising synthons in designing compounds with desired properties. In this respect the investigation of reactions of 3-nitro- and 3-bromo-3-nitroacrylates I IV with C-nucleophiles is of a great interest, in particular, the reaction with 2-phenyl-1,3-indandione which possesses its proper importance as
an anticoagulant and which is used in the treatment of thrombosis as a phenindione medicine [6, 7].
Our studies demonstrated that the mentioned substrates I IV readily added 2-phenyl-1,3-indanedione (in benzene solution at equimolar reagents ratio in the presence of a catalytic amount of triethylamine) forming adducts of a Michael condensation V VIII .
Compound V is a colorless viscous liquid, and com-pounds VI VIII are crystalline substances; their structure is confirmed by spectral methods. For instance, the IR spectra of adducts VII and VIII contain the absorption bands of b -dicarbonyl (1715 1750 cm 1), nitro (1350,1575 1580 cm 1) groups and multiple C=C bonds of the aromatic rings (1600 cm 1). It should be noted that the split bands in the region 1700 1750 cm 1 are typical of the b -diketo fragments [8], and the observed large distance between the bands of the symmetric and antisymmetric vibrations of the nitro group (D n ~ 230cm 1) is characteristic of the geminal location of a nitro group and a halogen atom [9]. In the 1H NMR spectra all the signals from the structural fragments of the compounds were revealed. In particular, the 1H NMR spectrum of compound VII contained a double set of proton signals from the methine and methyl groups corresponding to the existence of the compound as a mixture of two diastereomers in a ratio (VIIa ):(VIIb ) =12:1. According to the 1H NMR data the ethoxy analog VIII is stereo homogeneous. Compounds V VIII obtained may be regarded as precursors of the b -alanine containing a pharmacophoric fragment of 2-phenyl-1,3-indanedione.
Initial nitroacrilates I and II were synthesized by a modified published procedure [10], and alkyl 3-bromo-
X = H, R = Me (I, V ), Et (II, VI ); X = Br, R = Me (III, VII ), Et (IV , VIII ).
1243 3-NITRO- AND 3-BROMO-3-NITROACRYLA TES
3-nitroacrylates III and IV were prepared as described in [4].
2-(1-Methoxycarbonyl-2-nitroethyl)-2-phenyl-1,3-indanedione (V). Yield 76% (eluent benzene), R f0.36. IR spectrum,cm 1: 1735, 1710 (C=O), 1600 (C=C), 1560, 1380 (NO2). 1H, d, ppm: 3.56 s(3H, OCH3), 5.13 d.d (1H, H A, J AB 14.6, J AX 9.2 Hz), 4.33 d.d (1H, H B, J AB 14.6, J B X2.7 Hz), 4.74 d.d (1H, H X, J AX9.2, J B X 2.7 Hz), 7.31 8.06 m (9H, C6H4, C6H5). Found, %: C 64.68, 64.64; H 4.41, 4.40; N 3.95, 3.94. C19H15NO6. Calculated, %: C 64.59; H 4.28; N 3.96. 2-(2-Nitro-1-ethoxycarbonylethyl)-2-phenyl-1,3-indanedione (VI). Yield 82%, mp 133 135°C (from ethanol). IR spectrum, cm 1: 1750, 1730 (C=O), 1600 (C=C), 1560, 1380 (NO2). 1H NMR spectrum, d, ppm: 0.99 t (3H, CH3), 3.99 q (2H, OCH2), 5.13 d.d (1H, H A, J AB 14.6, J AX 9.8 Hz), 4.30 d.d (1H, H B, J AB 14.6, J B X 2.4 Hz), 4.70 d.d (1H, H X, J AX 9.8, J BX 2.4 Hz), 7.31 8.07 m (9H, C6H4, C6H5). Found, %: C 65.44, 65.42; H 3.95,
3.99; N 3.89, 3.90. C20H17NO6. Calculated, %: C 65.39;
H 4.66; N 3.81.
2-(2-Bromo-1-methoxycarbonyl-2-nitroethyl)-2-phenyl-1,3-indanedione (VIIa, b). Yield 22%, mp 174 176°C (from methanol); ratio of (VIIa):(VIIb) = 12:1. IR spectrum, cm 1: 1740, 1715 (C=O), 1600 (C=C), 1580, 1350 (NO2). 1H NMR spectrum, d, ppm: isomer VIIa 3.59 s (3H, CH3O), 6.33 d (1H, H A, J AB 4.9 Hz), 4.47 d (1H, H B, J AB 4.9 Hz), 7.33 8.07 m (9H, C6H4, C6H5); isomer VIIb 3.66 s (3H, CH3O), 6.42 d (1H, H A, J AB 4.3 Hz), 5.21 d (1H, H B, J AB4.3 Hz), 7.33 8.07 m (9H, C6H4, C6H5). Found, %: C 52.84, 52.85; H 3.32,
3.33; N 3.22, 3.23. C19H14BrNO6. Calculated, %: C 52.80;
H 3.26; N 3.24.
2-(2-Bromo-2-nitro-1-ethoxycarbonylethyl)-2-phenyl-1,3-indanedione (VIII). Yield 40% (eluent benzene), mp 133 136°C (from ethanol). IR spectrum, cm 1: 1735, 1715 (C=O), 1600 (C=C), 1575, 1350 (NO2). 1H NMR spectrum, d, ppm: 1.14 t (3H, CH3), 4.09 q (2H, CH2O), 6.38 d (1H, H A, J AB 3.7 Hz), 5.19 d (1H, H B, J AB 3.7 Hz), 7.33 8.11 m (9H, C6H4, C6H5). Found, %: C 53.99, 54.00; H 3.91, 3.93; N 3.39, 3.38. C20H16BrNO6. Calculated, %: C 53.83; H 3.61; N 3.14.
IR spectra were recorded on a spectrophotometer Infra-LYuM FT-02 from solutions in chloroform, c 0.1 0.001 mol l-1. 1H NMR spectra were registered on a spectrometer Bruker AC-200 (200 MHz) in deuterochloroform; the chemical shifts were measured relative to an external reference HMDS with an accuracy ± 0.5 Hz. The purification and isolation of individual compounds was performed by recrystallization and column chromatography on silica gel Chemapol 100/250 using Trappe solvents series. The homogeneity of compounds obtained was checked and the reaction progress was monitored by TLC on Silufol UV-254 plates, eluent a mixture hexane acetone, 2:1, development under UV irradiation and in iodine vapor.
The study was carried out under financial support of the Saint-Petersburg administration (grants PD06-1.3-185, M06-2.5K-379).
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