A. M. Hussein

POLYCYCLIC PYRIDINES: SYNTHESIS OF PYRIDOTHIENOPYRIMIDINES PYRIDOTHIENOTRIAZINES AND PYRIDOTHIENOTRIAZEPINES

Abstract Thienopyridines 3a-c were acetylated with Ac2O to afford the pyridothienopyrimidines 4a-c. Also 3a-c were treated with carbon disulfide in dioxan solution to give 5a-c. Diazotization of 3a-c gave the triazine derivatives 6a-c. Treatment of 3a-c with triethyl orthoformate in acetic acid gave 7a-c in good yield. Chlorination of 7a by POCl3, afforded the chlorine derivatives 8. Similarly diazotization of the ortho-aminohydrazide 3d give the corresponding azide 9 which was subjected to Curtius rearrangement in boiling xylene to give the imidazothienopyridine 10. Compound 12 was obtained by the reaction of 3d with either formic acid or trimethyl orthoformate. Compond 14 was also obtained by the reaction of 3d with ethyl chloroformate. Refluxing of 3d with methyl isothiocyanate gave 15. The interaction of 3d with acetylacetone furnished the pyrazolyl derivative 16. The ortho-aminonitrile 3e reacts with mixture of formic acid and formamide (1:1) to give 7a. whereas 3e reacts with formamide alone give 17. Treatment of 3e with carbon disulfide in boiling pyridine afforded 18. Also, acetylation of 3e with acetic anhydride afforded 4a. Finally, treatment of 3e with triethyl orthoformate in acetic anhydride afford 19. The reaction of 3e with phenyl isothiocyanate gave 20.

SOME RING CLOSURE REACTIONS WITH CYANOTHIOFORMAMIDES: NEW ROUTE FOR THE SYNTHESIS OF (IMIDAZOLIDINE, OXAZOLIDINE & PYRROLINE)-IMINOTHIONES, BENZOTHIAZOLOQUINAZOLINONES AND IMIDAZOQUINOXALINES

Abstract Cyanothioformarnides were reacted with isocyanates, isothiocyanates, aldehydes, acetylenedicarboxylic acid and anthranilic acids to produce imidazolidines, oxazolidines pyrroline, quinazolinones and benzothiazoloquinazolinones, respectively. Interaction of imidazolidineimino(thiones and dithiones) with o-phenylenediamines gave rise to imidazoquinoxalines and imidazoquinoxalinethiones, respectively.

SOME CYCLIZATION REACTIONS WITH 4-THIOHYDANTOIN: SYNTHESIS OF SOME NOVEL THIOPYRANOIMIDAZOLES, THIENOIMIDAZOLES AND IMIDAZOQUINOLINES AND SOME METAL COMPLEXES WITH BIOLOGICAL INTEREST

Abstract 4-Thiohydantoin (II) with chloroacetic acid, chloroacetanilides and cyanothioformamides gave thieno[2,3-d)imidazoles (IV, V and IX), respectively. α,β-Unsaturated nitriles and anthranilic acids reacted with (II) to produce thiopyrano[2,3-d]imidazoles (III) and imidazo[4,5-b]quinolines (VII). Some metal complexes were prepared and the antimicrobial activity of some selected compounds was also reported.

Studies with polyfunctionally substituted heteroaromatics: A facile route for the synthesis of polyfunctionally substituted N-aminopyridines, 1,2,4-triazolo[1,5-a]pyridines and isoquinolines

The reactions of formaldehyde and acetaldehyde with active methylene compounds, followed by reaction with cyanoacetic acid hydrazide 2, afforded N-aminopyridine-2-one derivatives 5a-f. In contrast, the reactions of cyanoacetic acid hydrazide 2 with aliphatic aldehydes and cyanothioacetamide afforded pyridinethione derivatives 11a-b. Also, the reactions of active methylene compounds with formaldehyde and cyanoacetamide afforded pyridin(1H)-2-one derivatives 12a-c. The reactions of 5b with aldehydes and ketones afforded compounds 13a, b, 14, and 15, respectively. The reactions of 5b with arylidinemalononitriles 16a,b afforded isoquinoline derivatives 19a,b. Compound 19b by hydrolysis gave the final product 20. Compound 20 could also be formed by hydrolysis of 5b to give 21, followed by the reaction with 16b.

Phenylacetone as Building Blocks in Heterocyclic Synthesis: Synthesis of Polyfunctionally-Substituted Pyridines, and fused Pyridines

Many pyridinethiones are biologically active. In view of our interest in developing efficient syntheses of polyfunctionally substituted heteroaromatics utilizing the readily obtainable enaminone 3 as starting materials. So, treatment of enaminone 3 with cyanothioacetamide or cyanoacetamide afforded the pyridinethione 5a and pyridone 5b. compound 5a reacted with α -halo- ketones in refluxing sodium ethoxide to give the thienopyridine derivatives 9a – e . Compound 5a reacted with methyl iodide to give 2-methylthiopyridine 10. Condensation of pyridinethione 5a with dimethylformamide-dimethylacetal gave the adduct 11 and with hydrazine hydrate afforded 12 . Compound 5a reacted with arylidenemalonitrile to give styryl derivatives 14a – d . Compound 14a – d also prepared from the condensation of 5a with the aromatic aldehydes under the same condition. Reflux of thienopyridine derivatives 9a – d with triethylorthoformat, acetic anhydride, carbon disulfide and sodium nitrite to give compounds 19 – 23 , respectively. The aminopyrazole 12 reacted with dimethylaminopropiophenone hydrochloride 24 or enaminone 30 in refluxing DMF to yield compound 26a – d . Treatment of 12 with 32 afforded 34 . Compound 34 can be also prepared from the reaction of 37 with aroylacetonitrile 31. Compound 12 reacted with DMF-DMA to give 37 , which reacted with compound 1 to give 38 prepared directly from reaction of 12 with enaminone 2 . Diazotization of 12 with nitrous acid followed by coupling with different active methylene reagents afforded the pyridothienotriazines 42a , b . Reaction of benzylideneacetophenone with 12 yielded the pyridopyrazolopyrimidine 44. Also, compound 12 reacted directly with active methylene to give the pyridopyrazolopyrimidine derivatives 46a , b .

POLYCYCLIC PYRAZOLES : ROUTES TO NEW PYRAZOLOAZINES

A number of substituted pyrazolo[3,4-b]pyridines and pyrazolo[4′,3′:5,6]pyrido[2,3-d]-pyrimidinones and -1,2,3-triazinones have been made, starting from 5-amino-3-methyl-1-phenylpyrazole-4-carbaldehyde.

N-1-Naphthyl-3-oxobutanamide in Heterocyclic Synthesis: A Facile Synthesis of Nicotinamide, Thieno[2,3-b]pyridine, and Bi- or Tricyclic Annulated Pyridine Derivatives Containing Naphthyl Moiety

N-1-Naphthyl-3-oxobutanamide (1) reacts with arylidinecyanothioacetamide 2a–c in ethanol/piperidine solution under reflux to yield the pyridine-2(1H)-thiones 6a–c. Compound 6a reacts with α-haloketones 7a–e to give the 6-thio-N-1-naphthyl-nicotinamides derivatives 8a–e, which cyclized to thieno[2,3-b]pyridine derivatives 9a–e. The reaction of compound 9a with hydrazine hydrate and formamide gives the thieno[2,3-b]pyridine carbohydrazide derivative 10 and pyridothienopyrimidine derivative 11, respectively. Reaction of 9a with benzoyl isothiocyanate gave thiourea derivative 12. Compound 12, upon treatment with alcoholic NaOH, gave pyridothienopyrimidine 13. Saponifications of 9a gave the amino acid 15, which affords 16 when refluxed in Ac2O. Treatment of compound 16 with AcONH4/AcOH gave 17. Diazotization and self-coupling of 9b gave the pyridothienotriazine 18. Also, diazotization of the ortho-aminohydrazide 10 give the corresponding azide 19, which was subjected to Curtius rearrangement in boiling xylene to give imidazothienopyridine 20. Reaction of 10 with either formic acid or triethylorthoformate and phenyl isothiocyanate gave the corresponding pyridothienotriazepines 22 and 23, respectively. The interaction of 10 with acetylacetone furnished the pyrazolyl derivative 24. The structures of the synthesized compounds were established from their analytical and spectral data.

STUDIES ON THE SYNTHESIS OF SOME PYRAZOLO[1,5=a]PYRIMIDINES BEARING SULFONAMIDO MOIETIES

Abstract A novel synthesis of pyrazolo[1,5-a]pyrimidine derivatives 4,5 and 9 bearing sulfonamide moieties from the reaction of aminopyrazoles 1 with [bis(methy1sulfanyl)methylidene]malononitrile 2, [arylamino(methylsulfanyl)methylidene]malonoNtrile 6 and ethyl [bis(methylsulfanyl)methylidene]cyano acetate 7 is reported.

The reactions of 4‐substituted‐7‐aminothieno‐[3,4‐d]pyridazines and 2‐methyl‐6‐aminothienopyridine‐5‐thione with electron‐poor olefins and acetylenes

Cycloadditions of thienopyridazines and a thienopyridine with electron-poor olefins and acetylenes as dienophiles are described. The nonisolable adducts undergo subsequent loss of hydrogen sulfide to give substituted phthalazines and substituted isoquinolines, respectively.

MOLECULAR REARRANGEMENTS OF SULFUR COMPOUNDS PART VIII. PYROLYSIS OF 2-(N-SUBSTITUTED CARBOXAMIDO-METHYLTHIO)-5-ARYLAMINO-1,3,4-THIADIAZOLE DERIVATIVES

Abstract Pyrolysis of 2-(N-substitutedcarboxamidomethylthio)-5-arylamino-1,3,4-thiadiazoles(I-III) at ca 210°C in boiling tetralin for 8 hrs or neat at ca 250°C for 5 hrs affords hydrogen sulfide, aryl isothiocyanate, arylcyanamide, benzimidazole derivatives, 4-aryl-1,2,4-triazole, thioglycolicanilides, 4-aryl-δ2-triazoline-5-thione and 3-aryl-2-thiohydantoin derivatives. A free radical mechanism has been suggested to account for the obtained products.