V. L. Savel'ev

Investigations of pyrans and related compounds

The action of phosphorus oxychloride in DMFA on 4-hydroxy-3-nitrocoumarin has given 4-chloro-3-nitrocoumarin, by the reaction of which with amines and ammonia 4-amino-3-nitrocoumarins have been synthesized; some of their physicochemical properties have been studied.

Synthesis and pharmacological activity of 4H-[1]-benzopyrano[3,4-d]imidazol-4-ones

pendent stretching vibrations of C=C and C=N bonds). The stretching vibrations of the NH group in the spectrum of compound IIa appear at 3400 and 3230 cm-i; the weak band at 3100 cm -~ present in the spectra of imidazoles IIa-j corresponds to the vibrations of the CH bonds. In the PMR spectrum of compound IIf there are Unresolved groups of signals at 0.8-2.2 ppm (7H, CHsCH2CH2--), a triplet signal (J = 7.5 Hz) at 4.5 ppm (2H; --CH2N--), and sevemal signals at 7-8.2 ppm (5H; C~H~ and 2-H). In the mass spectra of these compounds, there is a molecular ion peak that, in general, has maximum intensity.

Synthesis and study of the properties of 4-substituted 3-aminomethylcoumarins

The aminomethylation of 4-hydroxycoumarin gave 3-pyrrolidinomethyl- and 3-piperidinomethyl-4-hydroxycoumarins, which were converted to 4-chloro derivatives by the action of phosphorus oxychloride. A number of 3-pyrrolidinomethyl- and 3-piperidinomethyl-4-aminocoumarins were synthesized by reaction of the 4-chloro derivatives with various amines, and some of their properties were studied.

Investigations on pyran and related compounds

The reaction of 2-acylaminochromones with formaldehyde and primary amines leads to derivatives of 1,2,3,4-tetrahydrochromeno[2,3-d]pyrimidine, and with aromatic aldehydes in the presence of triethylamine, to arylidene-3,3′-bis(2-acylaminochromone)s. The chlorination of 2-acylaminochromones has yielded the corresponding 3-chloro derivatives. The aminomethylation of 2-aminochromone takes place in position 3.

New methods for the synthesis of amides of benzo[b]thiophene-2carboxylic acid

The reaction of 3-bromothiocoumarin with nitrogen bases, during which the thiocoumarin system is converted to a benzothiophene system, was studied. A new method for the synthesis of amides of benzo[b]thiophene-2-carboxylic acid is proposed.

Synthesis and pharmacological activity of 4-amino-3-nitrocoumarins

The synthesis of compounds Ia-d, f, g, i, J, m, and n has already been described [6]. The remaining compounds Ie, h, k, Z, and o-q were prepared according to the method described in [6], by reacting 4-chloro-3-nitrocoumarin (II) with 2 moles of the corresponding amine dissolved in absolute benzene or dimethyl sulfoxide (see Table i). Reaction takes place very rapidly and the products are formed in high yield; they are all intensely yellow, crystalline substances. Their structures were confirmed by elemental analysis and by spectroscopic means. The infrared spectrum of I in chloroform has absorption bands characteristic of the carbonyl group (1720-1730 cm-1), the nitro group (~as 1550-1560 and ~s 1310-1320 cm-1), and the double bond of the coumarin ring (1605-1615 cm-1).

Synthesis and Neurotropic Activity of 1-Substituted 4H-[1]Benzopyrano[3,4-d][1,2,3]triazol-4-ones

Some of the compounds belonging to condensed systems containing a coumarin ring annelated at positions 3 and 4 with various nitrogen-containing heterocycles were reported to possess a high affinity to benzodiazepine receptors [1 – 6]. Previously [7], we have synthesized 4H-[1]benzopyrano[3,4-d]imidazol-4-one derivatives exhibiting a neurotropic activity of either depriving or stimulating types, depending on the substituent at the nitrogen atom. In continuation of the search for new compounds possessing neurotropic activity, we have synthesized and biologically tested a series of new compounds belonging to the still insufficiently studied system of 4H-[1]benzopyrano[3,4-d][1,2,3]triazol-4-one with various dialkylaminoalkyl radicals in position 1 of the triazole ring. The target products were synthesized using an earlier developed scheme [8] proceeding from 3-nitro-4-chlorocoumarin (I). Reactions of this initial compound with the corresponding dialkylaminoalkylamines in dichloroethane solutions yield 3-nitro-4-dialkylaminoalkylamino)coumarins (IIa – IIh). Hydrogenation of these products in ethanol in the presence of 10% Pd on charcoal leads to the corresponding 3-amino derivatives (IIIa – IIIh). Treatment of the latter compounds with sodium nitrite in a 18% aqueous hydrochloric acid solution yields the target 1-(dialkylaminoalkyl)-4H[1]benzopyrano[3,4-d][1,2,3]triazol-4-one hydrochlorides (IVa – IVh). The proposed structures of the synthesized compounds are confirmed by the results of elemental analyses and by the data of IR and H NMR spectroscopy. The IR spectra of compounds IIa – IIh contain the characteristic absorption bands due to carbonyl groups (1725 – 1702 cm – ), double bonds of the coumarin cycle (1620 – 1600 cm – ), and nitro groups (1560 and 1320 cm – ). In the spectra of compounds IIIa – IIIh, the frequency of carbonyl vibrations decreases to 1685 – 1660 cm – 1 and a new band (assigned to the bending vibrations of 3-NH2 group) appears at 1630 – 1610 cm – . The IR spectra of compounds IIa – IIh and IIIa – IIIh measured in chloroform solutions display absorption bands due to stretching vibrations of the NH groups in position 4 (3300 – 3100 cm – ).

Properties of 4H-[1]benzopyrano[3,4-c]-[1,2,5]-selenodiazol-4-one

Abstract4H-[1]benzopyrano[3,4-c][1,2,5]selenodiazol-4-one has been synthesized by the reaction of 3,4-diaminocoumarin with selenous acid and its reaction with several nucleophiles (alkali, ammonia, amines, hydrazine hydrate) and its nitration have been studied. Using PMR spectroscopy, a comparative kinetic study of the opening of the lactone ring in 6,8-dinitro-4H-[1]benzopyrano[3,4-c][1,2,5]seleno- and thiadiazol-4-ones has been carried out.

N-[3-nitro(amino)coumarin-4-yl]anthranilic acid amides. Synthesis of 6,7,8,13-tetrahydro[1]benzopyrano[4,3-b][1,4] benzodiazepine-6,8-dione

The reaction of 3-nitro-4-chlorocoumarin with anthranilic acid was used to synthesize N-(3-nitro-4-coumarinyl)-anthranilic acid, from which, through the acid chloride, we obtained a number of amides, which were reduced to N-(3-amino-4-coumarinyl)anthranilic acid amides The latter are cyclized under the influence of hydrochloric acid to 6,7,8,13-tetrahydro[1]benzopyrano-[4,3-b][1, 4]benzodiazepine-6,8-dione, which was also obtained from N-(3-amino-4-coumarinyl)anthranilic acid by its thermolysis or treatment with hydrochloric acid.

Synthesis of 4H-[1]benzopyrano[3,4-c][1,2,5]thyadiazol-4-one and its reactions with some nucleophilic and electrophilic agents

The reaction of 3,4-diaminocoumarin with thionyl chloride gave 4H-[1]benzopyrano[3,4-c][1,2,5]thiadiazol-4-one (II), which was cleaved by the action of nucleophilic agents to the corresponding 4-(2-hydroxyphenyl)-1,2,5-thiadiazole-3-carboxylic acid derivatives. The nitration of II leads to the 8-nitro or 6,8-dinitro derivative; the latter was isolated in the form of 4-(2-hydroxy-3,5-dinitrophenyl)-1,2,5-thiadiazole-3-carboxylic acid.