Sh. H. Abdel-Hafez

ORGANIC SELENIUM COMPOUNDS. PART I: SYNTHESIS AND APPLICATION OF SOME NEW DIARYL-SELENIDES AND SELENONES CONTAINING AMINO ACID MOIETIES

Abstract 4′-Nitro-4-aminodiphenylselenide (1) reacts with chloroacetyl chloride giving 4′-nitro-4-chloroacetylaminodiphenylselenide (2) which undergo facile reaction with certain amines and hydrazine yielding 4′-glycylamino and hydrazinoacetylamino-4′-nitrodiphenylse lenides (3) and (5). Two moles of (2) react with one mole of piperazine and/or hydrazine to give 1,4-bis [p-N-(p′-nitro-diphenylselenido)aminocarbonylmethylene] piperazine (4) and 1,2-bis[p-N-(p′-nitro-diphenylselenido)aminocarbonyl-methylene]hydrazine (6). Condensation of (5) with aromatic aldehydes in the presence of glacial acetic acid yielded new Schiff bases (7). N-phthaloylglycyl chloride reacts with (1) in dioxane in the presence of trimethylamine to give N-(N′-phthaloylaminoacyl)-4-aminodiphenylselenide (8), hydrazinolyses of which affords N-(aminoacyl)-4-amino-4′-nitrodiphenylselenide (9). Compound (9) undergoes facile condensation with aromatic aldehydes in the presence of piperidine to give Schiff bases (10). Compound (2) interacts with malononitrile in the presence of K2CO3, giving 2-amino-(p′-nitrodiphenylselenido)-5-oxo-Δ2-pyrrolin-3-carbonitrile (11). Oxidation of (3,7) and (10) using H2O2/gl. acetic acid mixtures furnished the corresponding diarylselenones (12,13 and 14).

Selenium-Containing Heterocycles: Synthetic Investigation of 3-Amino-2-Ethylselenopyridine Carboxylate Using Sodium Borohydride

3-amino-4,6-dimethyl-2-ethylseleno[2,3-b]pyridine carboxylate (5) was prepared by a reaction of dipyridyl diselenide derivative (3) with sodium borohydride as a reducing agent followed by α-haloester. The reaction of 5 with hydrazine hydrate afforded the corresponding carbohydrazide 8. The benzylidene derivative 9 provided novel heterocycles of pyrimidoseleno pyridine and thiazinoseleno pyridine derivatives (10–12), upon treatment with triethylorthoformate, acetic anhydride, and carbon disulfide, respectively.

Synthesis of novel selenium containing sulfa drugs and their antibacterial activities

Synthesis of 3-[4-(N-substituted sulfamoyl)phenyl]-3,4-dihydro-4-oxo-7,9-dimethylpyri-do[3′,2′:4,5]selenolo[3,2-d]pyrimidines,7-[4-(N-substituted sulfamoyl)phenyl]-7,8-dihydro-8-oxo-3,4-diphenylpyrimido[4′,5′:4,5]selenolo [2,3-c]pyridazines and 1-[4-(N-substituted sulfamoyl)phenyl]-1,11-dihydro 11-oxo-4-methylpyrimido[4′,5′:4,5]selenolo[2,3-b]quinolines is reported. 4-Amino-N-pyrimidine-2-ylbenzene sulfonamide (a), 4-amino-N-(2,6-dimethylpyrimidin-4-yl)benzene sulfonamide (b), N-[(4-aminophenyl)sulfonyl] acetamide (c) with N-ethoxymethyleneamino of selenolo pyridine, selenolo pyridazine and selenolo quinoline derivatives respectively were obtained starting from 1-amino-N4-substituted sulfanilamides. Spectroscopic data (IR, 1H NMR, 13C NMR and Mass spectral) confirmed the structure of the newly synthesized compounds. Substitutedpyrimidines, pyridazines and quinolines were screened for antibacterial activity against gram-positive and gram-negative bacteria. Selenolo derivative of N-[(4-aminophenyl)sulfonyl] acetamide (substitutent of sulfacetamide c) showed strong bactericidal effect against all the tested organisms. Selenolo[3,2-d]pyrimidin (substitutent a) showed a good bactericidal effect against Serratia marcescens, Staphylococcus aureus and Escherichia coli. Compounds selenolo[2,3-c]pyridazine (substitutent b), selenolo[2,3-b]quinoline(substitutents c)) exhibited a moderate bactericidal effect against Serratia marcescens. None of the synthesized seleno pyridazines has a considerable antimicrobial activity against the tested organisms. The minimum inhibitory concentration (MIC) of the most active compound-3-[4-(N-acetyl sulfamoyl)phenyl]-3,4-dihydro-4-oxo-7,9-dimethylpyrido[3′,2′:4,5]selenolo [3,2-d]pyrimidine was 10 mg ml−1.

Synthesis, Antimicrobial Activity of Some New 2-Amino-4-(4′-phenylsulfanyl-phenyl)-thiazole Derivatives and Theoretical Studies of Their Schiff's Base

2-Amino-4-(4′-phenylsulfanyl-phenyl)-thiazole (2) has been obtained from reaction of 4-chloroacetyl diphenyl sulfide (1) with thiourea. Compound (2) reacted with active methylene derivatives, e.g., diethylmalonate or ethylcyano acetate to give fused thiazolo-pyrimidines (3–6) under variable conditions. Other substituted thiazolo-pyrimidines (7–9) also have been prepared by the reaction of (2) with some arylidine malonitriles (benzylidinemalononitrile and ethylbenzylidinecyano-acetate). On treatment of schiffs bases (10 a–c ) with phenylisothiocyanate, the corresponding thiazolo-s-triazines (11 a–c ) were formed. Reaction of (2) with carbon disulfide in the presence of concentrated aqueous sodium hydroxide and DMF as solvent gave the sodium salt of dithiocarboimidic acid which, on treatment with 1 mmol of ethyl iodide, gave monoethylated product (12). Reaction of (12) with anthranilic acid yielded (13). Interaction of (2) with 2 mmol of ethyl iodide afforded the diethylated product (14) which reacted with potassium salt of anthranilic acid to give (15). Also, (14) reacted with o-phenylenediamine yielded (16). The substituent effect on the stereochemistry of Schiffs bases (10 a–c ) was studied using Hyperchem (version 5). Compounds (2, 4, 6, 10 b , 12, 13, 14, 15) were tested to evaluate their antimicrobial activity.

Synthesis, Antimicrobial Activity, and 77Se NMR of Some New Pyrrole Derivatives Containing a Diphenyl Selenide Moiety

A simple and mild synthesis for pyrrolyl and pyrrolo[2, 3]pyrimidinyl diphenyl selenides is described based on the reaction of active methylene compounds with 4′-nitro-4-acetylaminodiphenyl selenide. The sensitivity of 77Se NMR spectra allowed differentiating the rather similar pyrrole compounds. The synthesized compounds were screened for their antifungal and antibacterial activities.

Condensed Thioxocyclopentapyridine (Isoquinoline)-1,2,4-azines

Pyrido(isoquinolino)-1,2,4-triazepines and pyrido(isoquinolino) pyrazolo-1,2,4triazepines were obtained from a reaction between o-diaminothioxocyclopentapyridine(isoquinoline), chalcones, diketones, esters, and aldehydes, respectively. It is shown that the more basic 1-NH2 (pyrido) and/or 2-NH2 (isoquinolino) group of the starting o-diamines participate in the formation of the azomethine bond of the seven-membered heteroring. Compounds (3, 6, 9, 12, 15, 17, and 19) are individual (TLC) and their structures are confirmed by the data from elemental analysis and spectroscopy.

Organic Selenium Compounds, Part IV: Synthesis and Applications of Some New Diaryl Selenides Containing Azomethine and Oxazole Moieties

3,3′-Diacetyloxy (2), 3,3′-dihydroxy (3), 4,4′-diamino (4), and 4-amino (5) diphenylselenide derivatives were prepared as new precursors for the title studies. Compound 6 was obtained by condensation of 4 with an appropriate aromatic aldehyde. Unsymmetrical diphenylselenides 7 and 8 were obtained by condensation of 4 and/or 5 with an aromatic aldehyde. Compound 7 undergoes facile condensation with the same aldehyde present in its arylidene moiety to yield 6, while condensation with another different aromatic aldehyde yielded unsymmetrical 4-arylideneamino diphenylselenide derivative 9. Oxidation of 6, 8, and 9 using lead tetra acetate and/or N-bromosuccinimide yielded symmetrical bis-(2-aryl benzoxazol-6-yl) (10), unsymmetrical 3′-hydroxy, 2-aryl benzoxazol-6-yl selenides (11), and 2-aryl benzoxazol-6-yl, 2′-aryl′ benzoxazol-6′-yl selenide derivatives (12), respectively. Compound 10 was prepared in one-pot unequivocal synthesis by fusion of 4 with the appropriate aromatic aldehyde, while 12 was prepared by fusion of 4 with two different aromatic aldehydes. In certain cases, 6 and 9 were heated on a direct flame until complete homogeneity afforded the corresponding 10 and 12. The structures of the synthesized compounds are based on physical data, IR, 1H NMR, 13C NMR, chemical means, and mass spectral data. Some of the synthesized compounds were biologically tested. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Organic Selenium Compounds. Part II. Synthesis and Antibacterial Activity of Some New Symmetrical Diarylselenides Containing Thiazolyl, Thiazolidin-4-Onyl, Azetidin-2-Onyl, Triazolin-1-YL and Glycyl Moieties

GRAPHICAL ABSTRACT Abstract 4,4′-Dimonochloroacetyl diphenylselenide (2) was prepared as a new precursor for the title studies by chloroacetylation of diphenylselenide (1). 2 interacts with thiourea to afford 4,4′-di(2″-aminothiazol-4″-yl)diphenylselenide (3). Condensation of 3 with aromatic aldehydes in the presence of a catalytic amount of dry piperidine furnished aldimines (4). Interaction of 4 with mercaptoacetic acid afforded 4,4′-di(2″-(2‴-substituted phenyl-3‴-thiazolo-4‴-thiazolidinon)-3‴-yl)diphenylselenides (6). Schiff bases 4 interact with mono chloroacetyl chloride in dry dioxane and triethylamine produced 4,4′-di(2″-(4‴-substituted phenyl-3‴-chloro-2‴-azetidinon-1‴-thiazolo)-1‴-yl)diphenylselenides (8). 1,3-Dipolar cyclonucleophilic addition of diazomethane to certain of 4 gave 4,4′-di(2″-(5‴-substituted phenyl-Δ2-1‴,2‴,3‴-triazoline thiazolo)-1‴-yl)diphenylselenides (10). 2 interacts with secondary heteroalicyclic amines to afford 4,4′-diglycyl diphenylselenides (11). The structures of the synthesized compounds are based on correct physical data, IR, 1H NMR, 13C NMR, and by chemical means. Some of the synthesized compounds were biologically tested.