Synthesis of 1 , 4-Dihydropyridines Bearing a Carbamate Moiety on the 4-Position

A good range of 1,4-dihydropyridines bearing a carbamate moiety on the 4-position were synthesized from the primary reaction of different hydroxyaldehydes with phenyl isocyanates and the subsequent reaction of the obtained carbamates with methyl acetoacetate in the presence of ammonium fluoride. When phenyl isothiocyanate was used in place of phenyl isocyanate in the same condition, the reaction did not take place.

The most interesting aspect of dihydropyridines can be attributed to the coenzyme reduced nicotinamide adenine dinucleotide (NADH) and the unique ability of these compounds in biological systems to reduce unsaturated functionalities and also strained ring systems (carbonyls, conjugated olefins, epoxides, etc.) [32].Although 1,4-dihydropyridines with various aromatic, heteroaromatic [33], aliphatic, and sugar [34] substituents at C4 have been reported, there is no report of 1,4-dihydropyridines bearing carbamate substituent at C4.

Result and Discussion
We decided to develop the chemistry of this class of compounds and also provide a clean and easy work-up procedure.In continuation of our researches on the synthesis of heterocycles [35][36][37][38][39][40][41], we herein report a good range of 1,4dihydropyridines which have a carbamate moiety on the 4position.They were synthesized from a primary reaction of different hydroxyaldehydes with phenyl isocyanates and the subsequent reaction of the obtained carbamates with methyl acetoacetate in the presence of ammonium fluoride Scheme 1: Preparation of different carbamates from phenyl isocyanates and aldehydes.(Scheme 1 and Table 1).The obtained carbamates (R  CHO, 1a-f) will then react with methyl acetoacetate in the presence of ammonium fluoride to give different 1,4-dihydropyridines (2a-f, Scheme 2 and Table 2).
All compounds were characterized by 1 H NMR and IR.In the 1 H NMR spectrum of the 1,4-dihydropyridines a peak at 4.3-4.92ppm belongs to the proton at C-4 position.In the IR spectrum, a strong absorbance peak for the N-H group of the corresponding 1,4-dihydropyridines appears at 3277-3336 cm −1 (Figure 1, see Supporting Information available online at http://dx.doi.org/10.1155/2013/495982).

Experimental
All reagents were purchased from the Merck and Aldrich chemical companies and used without further purification.Products were characterized by spectroscopy data (FT-IR, 1 H NMR spectra).The NMR spectra were recorded in CDCl 3 , acetone, and DMSO. 1 H NMR spectra were recorded on a Bruker Avance DRX 90 MHz instrument.The chemical shifts () are reported in ppm relative to the TMS as internal standard.FT-IR (KBr) spectra were recorded on a Perkin-Elmer 781 spectrophotometer.Melting points were taken in open capillary tubes with a BUCHI 510 melting point apparatus and were uncorrected.The elemental analysis was performed using Heraeus CHN-O-Rapid analyzer.TLC was performed on silica gel polygram SIL G/UV 254 plates.

General Procedure for the Synthesis of Carbamates (1af).
A mixture of hydroxybenzaldehydes (1.0 mM) and phenyl isocyanate derivatives (1.0 mM) was stirred in ethyl acetate or Scheme 2: Preparation of different 1,4-dihydropyridines from carbamates and methyl acetoacetate.solvent-free at 70 ∘ C in an appropriate time, and progress of the reaction was monitored by TLC (Scheme 1, Table 1).After completion, the suspension was cooled, ethyl acetate evaporated, the solid was crystallized in ethanol to get the pure carbamates, and the obtained crystals were characterized by 1 H NMR and IR.

Typical Procedure for the Synthesis of 1,4-Dihydropyridines (2a-f).
A mixture of carbamate (1.0 mM), methyl acetoacetate (2.0 mM), and ammonium fluoride (2.0 mM) was stirred in ethyl acetate at 80 ∘ C for appropriate time, and progress of the reaction was monitored by TLC (Scheme 2, Table 2).After completion, the suspension was cooled, ethyl
a Isolated yield.b Reaction took place in ethyl acetate.
a Isolated yield.