2,6‐Diaryl‐4,4‐disubstituted‐4H‐thiopyran: Source for spiro heterocycles

Abstract

The 1,5-diaryl-3,3-disubstituted-1,5-pentanedione on reaction with ammonium acetate, phosphorus pentoxide and phosphorus pentasulfide gave respective 1,4-dihydropyridine, 4H-pyran and 4H-thiopyran. Novel spiro heterocycles have been obtained by the cyclocondensation of 4H-thiopyran with hydrazine, hydroxylamine, urea and thiourea.J. Heterocyclic Chem., 39, 649 (2002).As a result of our sustained efforts in the search for new and versatile multi-functional reactive intermediates, recently we have reported the preparation of 1,5-diaryl-3,3-disubstituted-1,5-pentanediones 1 and 2 by the reaction of phenacyl bromide with dimethyl malonate and ethylcyano acetate [1]. The presence of dicarbonyl functionality in 1 and 2 enabled us to incorporate N, O and S as heteroatoms in them [2]. This gave scope for us to design and develop hitherto unknown spiro heterocycles by exploiting the gem diester or cyano ester groups of 1,4-dihydropyridine (3 and 4), 4H-thiopyran (5 and 6) and 4H-pyran (7 and 8). In fact, during the last decade we were actively involved in the syntheses of several spiro-heterocycles [3]. In further development of this synthetic strategy, we have now considered the reactivity of the 2,6-diaryl-4,4-disubstituted-4H-thiopyran(5 and 6) with hydrazine, hydroxylamine, urea and thiourea.The synthetic method involves the reaction of 1,5-diaryl-3,3-dimethoxycarbonyl-1,5-pentanedione (1) or 1,5-diaryl-3-cyano-3-ethoxycarbonyl-1,5-pentanedione (2) with ammonium acetate in acetic acid, phosphorus pentasulfide in xylene and phosphorus pentoxide in dry benzene under reflux conditions to obtain 2,6-diaryl-4,4-dimethoxycarbonyl-1,4-dihydropyridine (3) or 2,6-diaryl-4-cyano-4-ethoxycarbonyl-1,4-dihydropyridine (4), 2,6-diaryl-4,4-dimethoxycarbonyl-4H-thiopyran (5) or 2,6-diaryl-4-cyano-4-ethoxycarbonyl-4H-thiopyran (6) and 2,6-diaryl-4,4-dimethoxycarbonyl-4H-pyran (7) or 2,6-diaryl-4-cyano-4-ethoxycarbonyl-4H-pyran (8) respectively (see Scheme 1 and Table 1) . Displacement of the oxygen atom in 7 or 8 on treatment with excess phosphorus pentasulfide in boiling xylene also gave 5 or 6. The absence of carbonyl absorption (ArCO) around 1690 in IR spectra of 3-8 indicated their formation. Further 3 or 4 showed a band around 3350-3450 for (NH). The 1 H NMR spectra of 3-8 showed a singlet in the region 5.22 -5.86, which accounts for C 3 -H and C 5 -H protons. However in case of 3 and 4 a singlet was observed around 9.02 -9.20 for NH which disappeares on deuteration. The 13 C NMR spectra of 3-8 exhibited resonance signals at 142.15 -152.28 (C 2 and C 6 ), 91.78 -120.54 (C 3 and C 5 ) and 41.24 -45.67 (C 4 ) which also support their structures (Table 3). The cyclocondensation of 5 with hydrazine, hydroxylamine, urea and thiourea in the presence of sodium methoxide resulted in the formation of 7,9-diaryl-8-thia-2,3-diaza-spiro [4,5]deca-6,9-diene-1,4-dione (9), 7,9-

Antiselective Three‐Component Mannich Reactions in Thiopyran‐4‐one System

“…Thiopyran structures constitute as one of the most important classes of sulfur containing heterocycles because of their usefulness in accessing certain natural and unnatural products . In addition, there is a possibility to remove the sulfur atom of the thiopyran unit at the final stage of multistep syntheses.…”

2,6‐Diaryl‐4,4‐disubstituted 1,4‐dihydropyridines: Source for spiro heterocycles

“…The synthesis involves the reaction of 1,5-diaryl-3,3-dimethoxycarbonyl-1,5-pentanediones (1a-c)/ 1,5-diaryl-3-cyano-3-ethoxycarbonyl-1,5-pentanediones (2a-c) with ammonium acetate in acetic acid under reflux conditions to give 2,6-diaryl-4,4-dimethoxycarbonyl-1,4-dihydropyridines (3a-c)/2,6-diaryl-4-cyano-4-ethoxycarbonyl-1,4-dihydropyridines (4a-c) [6]. The gem-dicarboxylate or gem-cyano ester on condensation with hydrazine hydrate, hydroxylamine hydrochloride, urea, and thiourea would furnish pyrazole, isoxazole, pyrimidine, and thiopyrimidine derivartives.…”

Studies with β-Oxoalkanonitriles: Simple Novel Synthesis of 3-[2,6-Diaryl-4- pyridyl]-3-oxopropanenitriles

“…Consequently, a method for their synthesis was developed. Reaction of phenacyl bromide ( 1a ) with ethyl cyanoacetate ( 2 ) afforded the dialkylated derivative 3a [ 21 ]. Similarly, 3b was obtained by reacting 1b with ethyl cyanoacetate.…”

“…Ethyl 2-cyano-4-oxo-2-(2-oxo-2-phenylethyl)-4-phenylbutanoate ( 3a ): Yield: 2.79 g (80%); mp 140 o C (lit. [ 21 ] mp 141 o C); IR υ = 2250, (CN), 1722 (CO, ester), 1689 (CO, benzoyl) cm -1 ; 1 H-NMR δ = 1.22 (t, 3H, CH 3 ), 3.95 (d, 2H, CH 2 ), 4.03 (d, 2H, CH 2 ), 4.19 (q, 2H, CH 2 ), 7.56-8.01 (m, 10H, Ar-H) ppm; MS, m/z (%) 349 (M + , 20), 276 (30), 244 (50), 105 (100), 77 (80); Anal. Calcd.…”