Studies of Thiazolopyridines,Part 6: Synthesis and Antimicrobial Evaluation of Some Novel Thiazolo[3,2-a] Pyridine and Thiazolo[2′,3′:6,1]-pyrido[2,3-d]pyrimidine Derivatives

Condensation of thiazolinone 1 with aromatic aldehydes yielded the corresponding methylidene derivatives 2a–f. Cyclization of compounds 2a–f with arylidenemalononitrile 3 (1:1 molar ratio) in ethanol in the presence of piperidine furnished the novel thiazolo[3,2-a]pyridines 5a–v, via Michael adduct 4. Compounds 5p, r were cyclized with malononitrile in the presence of piperidine to yield thiazolo[3,2-a][1,8]naphthryidines 7a, b. Thiazolo-[2′,3′:1,6]pyrido[2,3-d]pyrimidine 9a–cwere obtained by cyclization of compounds 5c, p, r with formic acid. The structure of the synthesized compounds was established by analytical and spectral data. Also, some of the synthesized compounds were screened for antimicrobial activity in vitro.     

Acetoacetanilides in Heterocyclic Synthesis,Part 1: An Expeditious Synthesis of Thienopyridines and Other Fused Derivatives

3-Oxo-N-{4-[(pyrimidin-2-ylamino)sulfonyl]phenyl}butanamide 1 reacts with arylidinecyanothioacetamide in refluxing ethanolic TEA to give the pyridinethione 2 rather than thiopyrane 4. Compound 2 reacts with α-haloketones to give the s-alkylated derivatives 7a–e. Compound 7a–e undergoes cyclization into thieno[2,3-b]pyridine derivatives 8a–e. The saponification of 8a gives the amino acid 9, which affords 10 when refluxed in Ac₂O. The treatment of 10 with NH₄OAc/AcOH gives 11. Compound II is also obtained when 8e is refluxed in Ac₂O. The reaction of 8a with hydrazine hydrate gives 12 and with formamide gives 13. Compound 13 also is obtained from the reaction of 8e with triethylorthoformate. The acetylation of 8a with Ac₂O gives the amide derivative 14, which, on treatment with aromatic amines, affords 15a–c. Compounds 15a–c are cyclized with H₂SO₄ to 16a–c. Compound 16 is obtained also from the acetylation of compound 8c, d by Ac₂O. Reactions of compound 8e with CS₂ in refluxing dioxane afford 17. The diazotization and self-coupling of 8e give the pyridothienotriazine 18. Finally, the chloronation of compound 13 with POCl₃ affords the chloride derivative 19.     

Studies on Quinazolines. Part III. Synthesis of Some Fused-Ring Cationic and Mesoionic Derivatives of the 1,3-Thiazolo[3,2-c]quinazoline Ring System

4-Allylthio-2-arylquinazolines 4a–c undergo cyclization by action of bromine to furnish 5-aryl-3-bromomethyl-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium bromide 5a–c. Compounds 5a–c undergo ring opening by action of water under acid catalysis to afford the corresponding dibromide derivatives 6a–c. Bromination of 3-allyl-2-aryl-4(3H)quinazolinethiones 7a–c leads to 5-aryl-2-bromomethyl-2,3-dihydrothiazolo[3,2-c]quinazolin-4-ium bromides 8a–c. However, 5-aryl-1,3-thiazolo[3,2-c]quinazolinium-3-olate 10a–c were prepared by the cyclodehydration of the corresponding thioglycolic acids 9a–c with Ac₂O.     

DIBUTADIENYL PIPERAZINE,DIBUTADIENYL HOMOPIPERAZINES AND BUTADIENYL-SUBSTITUTED PIPERIDINES FROM MONOSUBSTITUTED HALODIENES

Compounds 3a–k were obtained from the reactions of compounds 1a–k with homopiperazine (2) in CH ₂ Cl ₂ . Compounds 1a–b, 1d–f, and 1h–l gave compounds 5a–b, 5d–f, and 5h–l with 2-methylpiperazine (4) in dichloromethane. Compounds 7c and 9c were obtained from the reactions of compound 1c with 4-ethoxycarbonyl piperazine (6) and 4-piperidinol (8) in CH ₂ Cl ₂ . Compounds 1a and 1f gave compounds 11a and 11f with 4-methylpiperazine (10), and compound 13f was obtained from the reactions of compound 1f with 4-methylpiperidine (12) in CH ₂ Cl ₂ .     

Pyridine-2(1H)-thione in Heterocyclic Synthesis: Synthesis of Some New Nicotinic Acid Ester,Thieno[2, 3-b]pyridine,Pyrido[3′, 2′: 4, 5]thieno [3, 2-d]pyrimidine,and Thiazolylpyrazolo[3, 4-b]pyridine Derivatives

Nicotinic acid esters 3a–c were prepared by the reaction of pyridine-2(1H)-thione derivative 1 with α-halo-reagents 2a–c. Compounds 3a–c underwent cyclization to the corresponding thieno[2, 3-b]pyridines 4a–c via boiling in ethanol/piperidine solution. Compounds 4a–c condensed with dimethylformamide-dimethylacetal (DMF-DMA) to afford 3-{[(N,N-dimethylamino)methylene]amino}thieno[2, 3-b]- pyridine derivatives 6a–c. Moreover, compounds 4a–c and 6a–c reacted with different reagents and afforded the pyrido[3′,2′:4, 5]thieno[3, 2-d]pyrimidine derivatives 10a–d, 11a–c, 12a,b, 14a,b, 17, and 19. In addition, pyrazolo[3, 4-b]pyridine derivative 20 (formed via the reaction of 1 with hydrazine hydrate) reacted with ethylisothiocyanate yielded the thiourea derivative 21. Compound 21 reacted with α-halocarbonyl compounds to give the 3-[(3H-thiazol-2-ylidene)amino]-1H-pyrazolo[3, 4-b]pyridine derivatives 23a–c, 25, and 27a,b.     

THE SYNTHESIS OF FLUOROHETEROCYCLIC KETENE AMINALS

The synthesis of fluoroheterocyclic ketene aminals was investigated. Fluorobenzyl ketene dithioacetals 1c reacted with nitric acid in the presence of concentrated sulfuric acid to give compound 2c. 1 reacted with diamines to afford 3–4. C-fluorobenzylation of 3–4 give the corresponding 5–8.     

Facile Synthesis of Some New Pyrazole-Based 2-Thioxo-4-thiazolidinone

5-Ethoxymethylene-2-thioxo-4-thiazolidinone (1) reacts with hydrazine hydrate at room temperature to afford 5-(hydrazinylmethylene)-2-thioxo-4-thiazolidinone (3). Compound 3 condensed with different aromatic aldehydes 6a–d in ethanol in the presence of a few drops of piperidine to give the corresponding Schiff’s bases 7a–d. On the other hand, compound 3 reacts with o-hydroxybenzaldehyde derivatives 8a and 8b in refluxing ethanol catalyzed by a few drops of piperidine to yield 1H-inadzolyl-2-thioxo-4-thiazolidinones 9a and 9b. Reaction of compound 3 with α-ketoesters 10a and 10b or α-diketones 10c–e in refluxing glacial acetic acid furnished the pyrazolyl-2-thioxo-4-thiazolidinone derivatives 11a–e. Also, compound 3 reacts with some different enaminones 12a–f in refluxing glacial acetic acid to afford the new pyrazolyl-2-thioxo-4-thiazolidinone derivatives 13a–f. Pyrazoles 15a–d was obtained via reaction of compound 3 with chalcones 14a–d in dimethylformamide (DMF). The structures of all the newly synthesized products were confirmed on the basis of their elemental and spectral data, and a plausible mechanism has been postulated to account for their formation.     

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS VI1–5: Utility of Lawesson's Reagent for Synthesis of Thiaphosphorine,Thioxanthene, and Thiaphosphole Derivatives

Arylidene malonate derivatives 2a–c reacted with Lawesson's reagent (1) LR in equimolar ratio to yield the oxathiaphosphorine derivatives 3a–c. The behaviour of LR towards cyclic ketones was also examined and yielded the thioxanthene derivatives 5a,b. On the other hand, arylidene pyrazolone 8 reacted with LR to give the phosphole 10. Aminobenzenethiophene 11 reacted with LR under reflux to produce the corresponding thiazaphosphorine 12.     

Green synthetic approaches: solventless synthesis of polyfunctionally substituted aromatics as potential versatile building blocks in organic synthesis utilizing enaminones and enaminonitriles as precursors

Abstract

A variety of 1,3,5-trisubstituted benzenes could be obtained upon heating enaminones in absence of solvent over montmorillonite-K-10. Heating mixtures of two different enaminones 2a–d have also afforded 1,3,5-trisubstituted benzenes 7b–d and 8b–d resulting from self-condensation of one enaminone with two molecules of the other enaminone. Heating enaminone 2b with ethyl propiolate afforded a mixture of triaroylbenzene 3b in addition to diaroylbenzoic acid esters 11 and 1,3,5-aroylbenzene dicarboxylate 12. On the other hand, reaction of enaminone derivative 2b with dimethyl acetylenedicarboxylate has afforded 2-oxopyran-4-carboxylic acid derivative 15. 2-Aminoprop-1-ene-1,1,3-tricarbonitrile 16 was reacted with enaminones to yield polysubstituted benzenes 19a–c. Likewise the reaction of 2-aminoprop-1-ene-1,1,3-tricarbonitrile 16 with benzylidenemalononitrile has afforded polysubstituted benzenes 24.     

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.     

Some Observations on the Base-Catalyzed Cyclocondensation of 2,6-Dihalobenzaldehydes,Ethyl Cyanoacetate,and Thiourea

The reaction of 2,6-difluorobenzaldehyde, 2-chloro-6-fluorobenzaldehyde, or 2,6-dichlorobenzaldehyde and ethyl cyanoacetate and thiourea, in the presence of potassium carbonate, yielded a mixture of the cis- and trans-5,6-dihydro-2-thiouracil derivatives 4a–c. Compounds 4a–c, which were found to be resistant to atmospheric oxidation even at high temperatures, were successfully dehydrogenated to 5a–c via prolonged heating with chloranil in toluene. Meanwhile, oxidation of the dihydro derivative 4b by heating in dimethylsufphoxide for 10 min yielded the corresponding 2-thiouracil 5b in 73% yield, in addition to the disulfide derivative 7 as a minor product.     

THE NOVEL MACROCYCLIC AND LINEAR-CHAIN THIOETHERS FROM PERCHLOROBUTADIENE AND DITHIOLES

Compounds 3a–c, 4a, b, 5a–c, and 6a, c were obtained from the reactions of perchlorobutadiene (1) with 1,4-butanedithiol (2a), 1,5-pentanethiol (2b), and 2.2′-(ethlene-dioxyl)diethanethiol (2c) in ethanol in the presence of sodium hydroxide. Compounds 7a, b were obtained from the reactions of thioethers 3a, b with m-chlorperbenzoic acid in CHCl ₃ .     

New Approach to 4‐ and 5‐Aminopyrazole Derivatives

3‐Oxo‐3‐(pyrrol‐2‐yl)‐propanenitrile 1 coupled with aromatic diazonium salts to yield the corresponding 2‐arylhydrazones 2a–c. The latter products reacted with chloroacetonitrile and ethyl chloroacetate to yield 4‐aminopyrazole derivatives 5a–f. Reaction of 2 with hydrazine hydrate led to formation of 5‐amino‐4‐arylazopyrazole 6a–c. Compound 1 reacted also with trichloroacetonitrile to yield enamine 7, which in turn reacted with hydrazine hydrate to yield 5‐amino‐3‐(pyrrol‐2‐yl)‐pyrazole‐4‐carbonitrile 8.     

Some Cyclization Reactions with 2-Ethoxycarbonylmethylidene-4,5-Dihydro-4-Thiazolinone

2-Ethoxycarbonylmethylidine-4,5-dihydro-4-thiazolinone (1) was condensed with bis aromatic aldehydes such as terephthalaldehyde or 4,4′-bisformyl-diphenylether (2a,b) (2:1 molar ratio) and furnished bis-4-thiaozlidinones (3a,b). The reaction of (3a,b) with malononitrile and aromatic aldehydes (1:2:2 molar ratio) gave bis thiazolopyridines (4a–d). Bis-(thiazolopyridine) derivative (6) was obtained by reaction of 4-thiaozlinone (5c) with bis aldehyde (2b) in refluxing ethanol containing piperidine. Cyclization of 4-thiazolinones (5a,b) with different α-cyanocinnamonitriles gave thiazolo[3,2-a]pyridines (7a–d). Compound 9 was produced via the reaction of 8 with thioglycolic acid, which reacted with p-chlorobenzaldehyde to produce 10. Compound 10 was condensed with hydrazine hydrate and afforded 11. Compounds 12 and 16a,b were produced by the reaction of 9 with isatin and α-ethoxycarbonylcinnamonitriles, respectively.     

2-Ethanethioamide in Heterocyclic Synthesis: Synthesis and Characterization of Several New Pyridine and Fused Azolo- and Azinopyridine Derivatives

Pyridine-2(1H)-thione derivatives 3a,b were synthesized from the reaction of 1-(phenyl-sulfanyl)acetone (1) and cinnnamonitrile derivatives 2a,b. Compounds 3a,b reacted with different halogenated reagents 7a–f to give 2-S-alkylpyridine derivatives 8a–l, which could be, in turn, cyclized into the corresponding thieno[2,3-b]pyridine derivatives 9a–l. Compounds 9d,j reacted with acetic anhydride, formic acid, carbon disulfide, phenyl isothiocyanate, and nitrous acid to yield the corresponding pyrido[3′,2′:4,5]thieno[2,3-d]pyrimidine 12a,b, 15a,b, 17a,b, 20a,b, and pyrido[3′,2′:4,5]thieno[2,3-d][1,2,3]triazinone derivatives 22a,b, respectively.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

NOVEL N,S-SUBSTITUTED DIENES BY THE REACTION OF 2-NITROTHIOSUBSTITUTED HALODIENES AND PRIMARY AMINES

Mono(thio)substituted 1a–c gave compounds 3a–c and 5a with o-toluidin (2) and m-toluidin (4) in ether. Compounds 9a–c and 11a, b were obtained from the reaction of compounds 1a–c with p-fluorophenylamine (8) and p-fluorobenzylamine (10). Compounds 7a and 15c were obtained from the reaction of 1a and 1c with p-phenylendiamine (6) and o-phenylendiamine (14). Compound 13c was synthesized from the reaction of compound 1c with benzidine (2).     

2-氨基-4,6-二芳基吡啶的微波辐射促进合成

氯化N-氰甲基吡啶在微波辐射下于醋酸铵/醋酸体系中和4种查尔酮反应, 或直接与芳香醛和取代苯乙酮一锅煮反应, 高产率地生成了2-氨基-4,6-二芳基吡啶衍生物. 化合物的结构经过IR, ¹H NMR和HPLC-MS的表征.     

Studies on Pyrazine Derivatives,XLVI: The Synthesis of New Pyrazine Derivatives with N′-(Pyrazine-2-carbonyl)-hydrazinecarbodithioic Acid Methyl Ester Usage

4-Ω-alkylsubstituted derivatives of 1,2,4-triazole-2-thiones 2–7 were obtained using the high reactivity of N′-(pyrazine-2-carbonyl)-hydrazinecarbodithioic acid methyl ester 1 towards amines. In the reaction with cysteamine 1,3-thiazaethylene-1,2,4-triazole 8 formed. Aromatic amines and N-aminocycloalkylamines gave thiosemicarbazide derivatives 9–12 under the same conditions. The solution of sodium hydroxide caused the decomposition of compounds 11 and 12 and resulted in 4-piperidino- and 4-morpholino-thiosemicarbazides 13 and 14. Compounds 11 and 12 were cyclized to appropriate 4-substituted 1,2,4-triazole-2-thiones 16 and 17 under the influence of DBU or potassium carbonate solution. The heating of derivative 12 with sulfuric acid led to disubstituted 1,3,4-thiadiazole 18.     

Synthesis,characterization and antimicrobial study via new heterocyclic derivatives of trimethoprim

New compounds of trimethoprim heterocyclic derivatives were synthesized. These compounds were synthesized through the condensation reaction between trimethoprim with bromoacetic acid to yield compound 1. Several Schiff bases 2–7 have been synthesized by the condensation different aromatic aldehydes with compound 1. Compound 8 were formed from the reaction of sodium nitrite and acetyl acetone in presence of conc. hydrogen chloride to obtain the hydrazono derivative; then, Cyclocondensation of compound 8 with hydrazine hydrate, phenyl hydrazine and dinitrophenyl hydrazine respectively to yield compounds 9–11 in ethanol affording the pyrazoline derivatives. This work involves the synthesis of some 1,2,3-Triazoles derived from compound 1 by the action of sodium azide on the diazonium chloride salt to yield 5-azido-8-(3,4,5-trimethoxybenzyl)imidazo[1,2-c]pyrimidin-3(2H)-one 12. Finally, by reaction of 12 with acetyl acetone and ethyacetoacetate; respectively in sodium ethoxide/ethanol as a solvent to form compounds 13, 14. The structures of the compounds 1–14 were characterized by elemental analysis, spectral data and antimicrobial evaluation of the some newly synthesized compounds and found that the synthesized compounds are active against tested Gram positive and Gram negative bacteria like Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Proteus.     

Facile Synthesis of Triarylpyrimidines with Microwave‐Irradiated Reactions of N‐Phenacylpyridinium Chloride

In a system of ammonium acetate and acetic acid under microwave irradiation, N‐phenacylpyridinium chloride 1 reacted with 2 mol of aromatic aldehydes 2a–h to give 2,4,6‐triarylpyrimidine 3a–h, reacted with pyridinecarboxaldehyde 4a–c and acetophenone 5 to yield bipyridine derivatives 6a–c. The structure of the products was characterized with ¹H NMR, ¹³C NMR, IR, and mass spectroscopy.