Atef Hamed

The reaction of 2,4,6-tris(trimethylsiloxy)-1,3,5-triazine with chlorocarbenium ions: a new access to 1-oxa-3-azabutatrienium and 2-azaallenium salts

Abstract Chlorocarbenium salts 2a - d of the Vilsmeier-Arnold type react with the silylated isocyanuric acid 3 to give 1-oxa-3-azabutatrienium salts 1 under mild conditions. From reactions of diarylchloromethenium salts 2h - 1 with 3 and ketones or tertiary carboxamides high yields of 2-azaallenium salts 9 were obtained. A few chloro substituted 2-azaallenium salts 5 were prepared from 1b and carbonyl compounds. The mechanisms of the new reactions are discussed.

Synthesis of Acyclo C-Nucleosides OF Phenanthro[9,10-e][1,2,4]Triazino[3,4-c]-[1,2,4] Triazoles, and Their Precursors

Reaction of 3-hydrazinophenanthro [9, 10-e] [1, 2, 4] triazine (1) with aliphatic and aromatic aldehydes as well as monosaccharides gave the corresponding hydrazones 2a-g. The D-glucose analogue exists in the cyclic pyranosyl structure 5. Acetylation and partial acetylation of the sugar hydrazones were carried out. Cyclization of a number of hydrazones including the partially acetylated sugar hydrazones by thionyl chloride gave regioselectively the respective angular isomer 1-substituted phenanthro [9, 10-e] [1, 2, 4] triazino [3, 4- and not the linear isomer. The cyclization of 1 with acetic acid, however, gave regioselectively the linear isomer 19. The structural assignments were based on a model study whereby the angular 16a was found to be different from the linear isomer 19a obtained by the condensation of 4, 5-diamino-3-methyl-1, 2, 4-triazole with 9, 10-phenanthraquinone. Periodate oxidation of 2d gave 20 whose reaction with 1 gave 21.

The ritter reaction of α-chlorocarbenium ions; a synthesis of chloro substituted 2-azoniaallene salts

Abstract α-Chlorocarbenium ions, 9 , stabilized by allylic resonance, react with nitriles, 10 , to give chloro substituted 2-azoniaallene salts, 12 . The cation 12k abstracts chloride from the counterion SbCl 6 − to furnish the chloroimine 13k together with SbCl 5 . The hexachloroantimonates 12 can be transformed into unpolar chlorides, 13b,1 , and 17 , with ammonium chlorides. Compounds 13 and 17 are hydrolyzed to give N-acyl imidoyl chlorides, 14a,b , respectively the allophanate 18 . Electron-rich nitriles insert into the CCl bond of the 2-azoniaallene salts 12 to afford imidoyl chlorides, 151-p,16 .

Reactions of 1-oxa-3-azoniabutatriene salts with 1,3-dipoles

Abstract The nitrile N-oxide 4 undergoes a reversible cycloaddition to the carbonyl group of the 1-oxa-3-azoniabutatriene salts 3a–c to give the geminal dioxy substituted 2-azoniaallene salts 5a–c. Azibenzil 7 and 3a,d afford the 2-azoniaallene salts 8a,d. With the nitrone 11 the cumulene 3d reacts to yield the open-chain addition product 12. The salt 3a reacts with two equivalents of diazofluorene to give the β-lactamium salt 13, which can be hydrolyzed to afford the N-formyl-β-lactam 15. X-ray structural analyses of 5b and 8d confirm the proposed constitutions.1

Some reactions of 3-chloroisoindolium salts with nucleophiles: access to isoindole derivatives and ellipticine analogues as potential antiviral agents

3-Chloro-2-substituted-1-oxoisoindolium hexachloroantimonate (1) reacted with water, ethanol and dimethyl-cyanamide to give the corresponding phthalimide derivatives 2, 3 and 4 respectively. Reaction of 1a with nitriles afforded the intermediate 2-azoniaallene salts 5 which underwent cyclisation reaction upon heating to furnish the ellipticine analogues 6. The biological activities of 6a–e against HIV-1 and HBV viruses were determined.

Convenient Route to Efavirenz Analogues as Potential non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

Abstract Treating 2-chloro-4-(4-chlorophenyl)-6-methylbenzo[d]-3,1-oxazinium hexachloroantimonate (1) with one equivalent of alcohol or mercaptane led, after hydrolysis with aq. NaOH, to the formation of 4,4-disubstituted-1,4-dihydro-2H-6-methyl-3,1-benzoxazin-2-ones (3). Large excess addition of alcohol afforded either 4’-chloro-2-isocyanato-5-methylbenzophenone disubstitutedketal (4) or N-{2- [(4-chlorophenyl)dialkoxymethyl]-4-methylphenyl} alkylcarbamate (5). Reaction of 4 with primary amines furnished 1-{2-[(4-chlorophenyl)dialkoxymethyl]-4-methylphenyl}-3-substituted urea (6).

4′, x-Seco And 4′,x-4′,5′-Diseco C-Nucleosides From 2-Hydrazino-(3H)- Thieno [2,3-D] Pyrimidin-4-Ones

Cyclization of 2-hydrazino-5,6-dimethyl-3H-thieno[2,3-d]pyrimidin-4-one (1) with acetic acid gave 3,6,7-trimethyl-l,2,4-triazolo[3,4-a]thieno[2,3-d] pyrimidin-5-one (5) whose Dimroth rearrangement gave 2,6,7-trimethyl-l,2,4-triazolo[3,4-a]thieno[2,3-d]pyrimidin-5-one (11). Alternatively, 5 was obtained from the dehydrogenative cyclization of acetaldehyde 5,6- dimethyl-4-3H-oxo-thieno[2,3-d]pyrimidin-2-yl hydrazone (7). Reaction of 1 and 2 with a number of sugars gave the respective hydrazones 19 and 20. Those of the D-glucose exist in the cyclic pyranosyl structure in addition to minor amounts of the acyclic structure. Dehydrogenative cyclization of the sugar hydrazones gave the respective fused tricyclic compounds 25 and 26

On the Reaction of α,α-Dichlorocarbenium Ions with Isocyanates

Trichlormethanes 4 react with two equivalents of n-alkyl isocyanates R2-NCO in the presence of SbCl5 to furnish the 2,2-dichloro-5,6-dihydro-6-oxo2H-1,3,5-oxadiazinium salts (9). The structure of these heterocycles is confirmed by an X-ray analysis of 9d (R1 = ClC = CCl2, R2 = Et). p-Tolyl isocyanate is Friedel-Crafts alkylated by 4b in the presence of SbCl5. Subsequent ring closure affords the quinolinium salt 13, which is hydrolyzed to give inter alia the quinolone 16.

Facile Synthesis of Non-nucleoside Compounds Starting from α-Chlorocarbenium Ions and Isocyanates as Potential HIV-1 Reverse Transcriptase Inhibitors

Chloro(phenyl)carbenium hexachloroantimonate salts react with isocyanates to afford either isoindolium (1) or benzoxazinium salts (2). Addition of one equivalent of alcohol to 2 led, after hydrolysis with aq. NaOH, to the formation of benzoxazin-2-ones 3. Treatment with a large excess of alcohol transformed the salts 1 and 2 to the corresponding isoindol-1-ones 11 and the isocyanates 5, respectively. Reaction of 5 with primary amines furnished the urea derivatives 6 in good yield. The biological activity of 6a - o against HIV-1 was determined. Graphical Abstract Facile Synthesis of Non-nucleoside Compounds Starting from α-Chlorocarbenium Ions and Isocyanates as Potential HIV-1 Reverse Transcriptase Inhibitors

On the Reaction of alpha,alpha-Dichlorocarbenium Ions with Isocyanates

Trichlormethanes 4 react with two equivalents of n-alkyl isocyanates R2-NCO in the presence of SbCl5 to furnish the 2,2-dichloro-5,6-dihydro-6-oxo2H-1,3,5-oxadiazinium salts (9). The structure of these heterocycles is confirmed by an X-ray analysis of 9d (R1 = ClC = CCl2, R2 = Et). p-Tolyl isocyanate is Friedel-Crafts alkylated by 4b in the presence of SbCl5. Subsequent ring closure affords the quinolinium salt 13, which is hydrolyzed to give inter alia the quinolone 16.