Scientific journal
European Journal of Natural History
ISSN 2073-4972

RECYCLIZATION OF 6-AMINO-5-CARBONITRILEFUROPYRANES UNDER THE ACTION OF NUCLEOPHILS

Anis´kova T.V., Timofeyeva Z.Yu., Yegorova A.Yu.

6-Аmino-4-aryl-2R-4H-furo[2,3-b]pyrane-5-carbonitriles are an important class of heterocyclic compounds of significant interest owing to their various chemical transformations and many opportunities of practical application (1, 2). These bifunctional compounds with cyano and amino groups in the vicinal position are promising initial substances for synthesis of sophisticated annealed heterocyclic systems.

The synthesis of the said compounds is based on Michael´s condensation of 5-aryl-3-arylmethylene-3H-furan-2-ones with malonic acid dinitrile under basic catalysis /1/.

The behavior of furopyranes 1, 2 under the action of a strong nucleophilic reagent (sodium alcoholate) was studied. The reaction was carried out at heating of equimolar amounts of sodium alcoholate and furopyranes in an ethanol solution during 4 hr.

p

1,3 R=C6H5, Ar =C6H4-Cl-2; 2, 4 R=C6H4-CH3-3, Ar =C6H4-Cl-2;

The reaction products were identified as 4-aryl-6-ethoxy-2R-furo [2,3-b] pyridine - 5-carbonitriles (3, 4) by their physicochemical and spectral characteristics.

The IR spectra of compounds 3, 4 contain the absorption bands of a cyano group (2215-2210 cm-1), the absorption band of a -C-O-C- bond within 1130-1120 cm-1, and no amino group absorption band. In the NMR1H spectrum a series of signals in a strong field is observed within 1.40-1.45 ppm and 3.90-4.00 ppm, corresponding to the protons of an ester fragment, the singlet of a furan ring proton is shown at 6.3-6.4 ppm, the signal of the methyl group protons of the aromatic substituent (for compound 4) is about 2.35 ppm.

The formation of a pyrane cycle of compounds 1, 2 due to intramolecular interaction of the hydroxylic and cyano groups is a reversible process [2]; under certain conditions the pyrane cycle may open with subsequent cyclization.

p

First, nucleophilic addition of an alcoholate anion by the α carbon atom of the pyrane cycle occurs with subsequent opening of the heteroring. Further attack of the unshared electronic pair of the nitrogen atom by the electron-deficient carbon atom of the lactonic system, cyclization, and aromatization result in formation of a pyridine structure.

EXPERIMENTAL

IR spectra were recorded on an FSM-1201 Fourier spectrometer in KBr tablets, the spectral range being 400-4000 cm-1. NMR1H spectra were obtained on a Bruker MSL-400 spectrometer within 20-25°C in CDCl3, TMS being the internal reference. The working frequency was 400 MHz.

4-Aryl-6-ethoxy-2R-[2,3-b]-pyridine-5-carbonitriles (3, 4). A mixture of 0.01 mol of 6-amino-4-aryl-2R-4H-furo[2,3-b]pyrane-5-carbonitrile (1, 2) and 0.01 mol of sodium alcoholate in an ethanol solution was heated for 2-3 hr, poured out in cold water, and neutralized with diluted HCl. The precipitated crystals were filtered out on a Schott filter and recrystallized from a hexane-IPA 1:1 mixture.

For 3: yield 75%; mp 160-1620C; 1H NMR, δ: 6.50 (1Н, s), 1.42 (3Н, t, OCH2СН3), 4.20 (2Н, m, ОСН2CH3), 7.25-7.68 (9Н, m, Ar). Found (%) C, 70.24; H, 4.33; N, 7.53. Calc. for C22H15ClN2O2 (%) C, 70.50; H, 4.03; N, 7.47

For 4: yield 68%; mp 157-1590C; 1H NMR, δ: 6.64 (1Н, s), 1.47 (3Н, t, OCH2СН3), 4.30 (2Н, m, ОСН2CH3), 7.15-7.50 (8Н, m, Ar). Found (%) C, 70.86; H, 4.60; N, 7.05. Calc. for C23H17ClN2O2 (%) C, 71.04; H, 4.41; N, 7.20

The work was supported by grant No MK-2952.2007.3 of President of Russian Federation for state support of young Russian scientists.

References:

  1. T.V. Anis´kova, A.Yu. Yegorova, and Z.Yu. Timofeyeva. Reactions of 3-arylmethylene-3H-furan-2-ones with malononitrile, a design method of furopyrane systems. Carbonylic Compounds in Heterocycle Synthesis. Coll. Book / Ed. Prof. A.P. Kriven´ko. Saratov, 2008. P. 36-38.
  2. F.S. Babichev, Yu.Ya. Sharanin, V.P. Litvinov, V.K. Promonenkov, Yu.M. Volovenko. Intramolecular interaction of nitrile and C-H, O-H, and S-H groups. Naukova dumka, Kiev, 1985.

The work was submitted to international scientific conference «Prospects for the development of university science», Dagomys (Sochi), 20-23 September 2008, came to the editorial office on 08.08.2008.