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.     

Facile Synthesis of Nicotinic Acid Derivatives with Unsymmetrical Substitution Patterns

Abstract

Two novel methods for synthesis of nicotinic acid derivatives with unsymmetrical substitution patterns were presented via ketene dithioacetals. The ketene N,S-acetals 2 reacted with β-ketoesters or β-cyanoesters to give 4-amino-5-cyano-2-alkyl-6-methylthio-nicotinic acid derivatives 3 or 2,4-diamino-5-cyano-6-methylthio-nicotinic acid ethyl ester 4. However, 6-amino-5-cyano-2-alkyl-4-methylthio-nicotinic acid esters 6 were obtained by the reaction of the ketene dithioacetals 1 and β-amino-crotonates.     

The Synthesis of Some Pyrazolyl- and Thiazolylthienopyridines

2-acetyl-3-amino-4,6-dimethylthieno[2,3-b]pyridine 1 reacted with dimethoxy-tetrahydrofuran in acetic acid and ethyl cyanoacetate in the presence of ammonium acetate or with NaNO₂ in the presence of an AcOH/HCl mixture to produce 2–4. Compound 2 reacted with aromatic aldehydes, semicarbazide hydrochloride, thiosemicarbazide, and phenyl hydrazine or with hydrazine hydrate to give compounds 5a–c and 11a–d, respectively.

Chalcone 5 reacted with hydrazines, hydroxylamine hydrochloride, or thiourea to produce compounds 6–9. Thiosemicarbazone 11b reacted with α -haloester to produce the corresponding thiazolidinone derivatives 12a, b ; also it reacted with ω -bromoacetophenone to give thiazoline derivatives 13a, b .     

A FACILE METHOD FOR THE SYNTHESIS OF NOVEL PYRIDINONE DERIVATIVES VIA KETENE N,S-ACETALS

A simple and easy method is provided for the synthesis of the novel pyridinone derivatives (3a–e), (8a–c) and (10a–c) by the reaction of ketene acetals (2a–e), (7a–c) and (9a–c) with ethyl cyanoacetate respectively. Compounds (3b–d) reacted with triethyl orthoformate to afford the pyridinone derivatives (4-6) respectively. Compound 7a reacted with ethyl acetoacetate or diethyl malonate to give thiazolopyridinone derivative 11 or 12 respectively.     

Acylation of Heterocyclic Ketene Aminals with Propionyl Chloride

Heterocyclic ketene aminals 1 or 2 reacted with propionyl chloride to give both the mono-N-and C-acylated products 4 and 5 or 6 and 7. While N-methyl heterocyclic ketene aminals 3 reacted with propionyl chloride under the same condition, the reaction took place in complexity. Besides N-and C-acylation, the O-attack and heterocyclic ring cleavage also occurred to give products 8 and 9.     

1,3-Disubstitutedpyrazole-4-caboxaldehyde in Heterocyclic Synthesis: A Novel Synthesis of Pyridine-2(1H)-thione and Fused Nitrogen and/or Sulfur Heterocyclic Derivatives

Pyridine-2(1H)-thione 5 was synthesized from the reaction of 3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) and cynothioacetamide (4). Compound 5 reacted with halogented compounds 6a–e to give 2-S-alkylpyridine derivatives 7a–e, which could be in turn cyclized into the corresponding thieno[2,3-b]-pyridine derivatives 8a–e. Compound 8a reacted with hydrazine hydrate to give 9. The latter compound reacted with acetic anhydride (10a), formic acid (10b), acetic acid, ethyl acetoacetate, and pentane-2,4-dione to give the corresponding pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine 13a,b, pyrazolo[3′,4′:4,5]thieno[3,2-d]pyridine 14 and thieno[2,3-b]-pyridine derivatives 18 and 20, respectively. Alternatively, 8c reacted with 10a,b and nitrous acid to afford the corresponding pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine 24a,b and pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine 26 derivatives, respectively. Finally compound 5 reacted with methyl iodide to give 2-methylthiopyridine derivative 27, which could be reacted with hydrazine hydrate to yield the corresponding pyrazolo[3,4-b]-pyridine derivative 29.     

Novel Syntheses and Reactions of Polynuclear Heterocyclic Derivatives Derived From Thioxopyridopyrimidine,With a New Ring System

Pyridopyrimidine derivatives 2 reacted with hydrazonoylchloride derivatives and yielded triazolopyridopyrimidines 6a–f. Compound 4b reacted with aliphatic acids and afforded triazolo-pyridopyrimidines 7a,b, and the reaction with carbon disulfide afforded 10-mercapto-triazolopyridopyrimidine (10). Moreover, the reaction of 4b with β -ketoesters afforded 10-pyrazolyl-pyridopyrimidines derivatives 11, 13, 14, and 15. Compound 4b reacted with nitrous acid to give tetrazolopyridopyrimidine 16, which reduced to 10-amino-derivative 17. On the other hand, the reaction of 4b with aromatic aldehydes afforded arylidines derivatives 18a–c, which were later cyclized to triazolo-pyridopyrimidines deivatives 19a–c. Finally, 4b reacted with α-haloketones to give triazines derivativrs 20, with new ring systems.     

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.     

Efficient method for the synthesis of 1,2,3-triazole functionalized isoxazolidine derivatives by 1,3-dipolar cycloaddition of nitrones with terminal olefins

1-Phenyl-1,2,3-triazole-4-carbaldehyde 1 was treated with different N-alkyl hydroxylamine hydrochlorides 2 using NaHCO₃ to obtain 1,2,3-triazole substituted N-alkyl nitrones 3a–c. The nitrones 3a–c were further reacted with different substituted olefins and furnished 2-alkyl-3-(1-phenyl-1H-1,2,3-triazol-4-yl)-5-(substituted)isoxazolidine derivatives 4a–p in high yields via 1,3-dipolar cycloaddition reaction.     

Regioselectivity and regiospecificity of benzoxazinone (2-isopropyl-4H-3,1-benzoxazinone) derivatives toward nitrogen nucleophiles and evaluation of antimicrobial activity

A novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared. The reaction of the benzoxazinone 3 with various nitrogen nucleophiles such as formamide and hydrazine hydrate and also the reaction of the isopropylquinazolinone 4 with hydrazonyl chloride have been shown to proceed with a high degree of regioselectivity at C(2). Spiro heterocycles have been found to play fundamental roles in biological processes and have exhibited diversified biological activity and pharmacological and therapeutical properties; thus reaction of acetohydrazides 10a–c afforded the spiro compounds 11a–c. The acetohydrazide derivative 7 reacted with carbon electrophiles such as acetylacetone, ethyl acetoacetate, acid chlorides, and benzaldehyde to give some interesting heterocyclic compounds 12–16, respectively. The structures of all the synthesized compounds were inferred by infrared, ¹H NMR, and mass spectra as well as elemental analyses. The antimicrobial activities of some of the synthesized products were preliminarily evaluated.     

2-Keto-3-mercaptocinchoninic Acids as Precursors for Novel Thiazino[6,5-c]quinoline-1,5-dione Derivatives

2-Keto-3-mercaptocinchoninic acid derivatives 1a and b react with Schiff's bases 2a–d in toluene at refluxing temperature to give thiazino[6,5-c]quinoline derivatives 4a–h. Also, refluxing of 1a and b with arylazomalononitriles 5a–d in acetic acid afforded the thiazolo[6,5-c]quinoline derivatives 7a–d. The structure of all the newly synthesized products was confirmed based on elemental and spectral data.     

Synthesis,reactions, and antioxidant activity of 3-(pyrrol-1-yl)-4,6-dimethyl selenolo[2,3-b]pyridine derivatives

Ethyl 4,6-dimethyl-3-(pyrrol-1-yl) selenolo[2,3-b]pyridine-2-carboxylate (2) was synthesized by the reaction of previously prepared ethyl 3-amino-4,6-dimethyl selenolo[2,3-b]pyridine-2-carboxylate (1) with 2,5-dimethoxytetrahydrofuran in acetic acid. The pyrrolyl ester (2) was converted into the corresponding carbohydrazide 3 which reacted with acetyl acetone, aromatic aldehydes, carbon disulfide in pyridine, and sodium nitrite to afford the corresponding dimethyl pyrazolyl 4, arylidene carbohydrazides 5a–d, oxadiazolyl thiole 6, and caboazide compound 8, respectively. The carboazide 8 reacted with different alcohols and amines to give the corresponding carbamates 9a–c and the aryl urea derivatives 10a–d. Heating of carboazide 8 in dry xylene afforded the pyridoselenolo-pyrrolopyrazinone 11. The latter compound was used as a versatile starting precursor for synthesis of other pyridoselenolo-pyrrolopyrazine compounds. The newly synthesized compounds and their derivatives were characterized by elemental analysis and spectroscopy (IR, ¹H-NMR, and mass spectra). Some of the newly synthesized pyrrolyl selenolopyridine compounds showed remarkable antioxidant activity compared to ascorbic acid.     

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.     

Synthesis of New Fused and Spiro Heterocyclic Systems from 3,5‐Pyrazolidinediones

4‐Bromo‐1‐phenyl‐3,5‐pyrazolidinedione 2 reacted with different nucleophilic reagents to give the corresponding 4‐substituted derivatives 3–8 . The cyclized compounds 9–11 were achieved on refluxing compounds 3 , 4 or 6_a in glacial acetic acid or diphenyl ether. 4,4‐Dibromo‐1‐phenyl‐3,5‐pyrazolidinedione 12 reacted with the proper bidentates to give the corresponding spiro 3,5‐pyrazolidinediones 13–15 , respectively. The 4‐aralkylidine derivatives 16_a‐c , were subjected to Mannich reaction to give Mannich bases 17_a‐c‐22_a‐c , respectively. 4‐(p‐Methylphenylaminomethylidine)‐1‐phenyl‐3,5‐pyrazolidinedione 23 or 4‐(p‐methylphenylazo)‐1‐phenyl‐3,5‐pyrazolidinedione 29 were prepared and reacted with active nitriles, cyclic ketones and N,S‐acetals to give pyrano[2,3‐c]pyrazole, pyrazolo[4′,3′:5,6]pyrano[2,3‐c]pyrazole, spiropyrazole‐4,3′‐pyrazole and spiropyrazole‐4,3′‐[1,2,4]triazolane derivatives 24–34 , respectively.     

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.     

SYNTHESIS OF NEW 3-SUBSTITUTED AND SPIRO 1,5-BENZODIAZEPIN-2-ONES UNDER PHASE-TRANSFER CATALYSIS CONDITIONS

1,3-Dihydro-4-phenyl-1,5-benzodiazepin-2-one 1 was treated with bromine in 1:1 molar ratio to get the corresponding 3-bromo derivative 2 which in turn reacted with different nucleophiles to get the corresponding 3-substituted derivatives 3–11. The cyclized compounds 4_a , 5_a , 7_a,b , and 9_a–c were achieved on refluxing compounds 4, 5, 6_a,b , or 8 _a–c respectively in diphenyl ether. Compound 1 was benzoylated with benzoyl chloride to give the corresponding 1-benzoyl derivative 12 which reacted with bromine in 1:2 molar ratio to yield the corresponding 3,3-dibromo derivative 13. Spiro benzodiazepines 14_a–d–16 were obtained by reacting compound 13 with the proper bidentates. Compound 1 was treated with formaldehyde and secondary amines or thiols to give Mannich bases or sulphides 17–21, respectively.     

Facile synthesis and characterization of novel pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one and pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine incorporating 1,3-diarylpyrazole moiety

4-(3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-6-phenyl-2-thioxo-1,2-di hydro-pyridine-3-carbonitrile (1) reacted with ethyl chloroacetate (2) in ethanolic sodium acetate solution to yield the corresponding ethyl (3-cyanopyridin-2-ylsulphanyl)acetate derivative 3. Intramolecular cyclization of compound 3 was achieved by its heating in DMF containing potassium carbonate to afford the corresponding ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate derivative 4 which reacted with hydrazine hydrate in refluxing pyridine to yield the starting material 3-aminothieno[2,3-b]pyridine-2-carbohydrazide derivative 7. Compound 7 reacted with different reagents such as triethylorthoformate, formic acid, acetic acid and acetic anhydride to afford the target molecules pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives 8–10, 12 and 13 in good to excellent yields. On the other hand, pyridine-2(1H)-thione derivative 1 reacted with hydrazine hydrate in refluxing pyridine to give the other starting material 3-amino-1H-pyrazolo[3,4-b]pyridine derivative 20 which reacted with acetylacetone under reflux to afford the target molecule pyrido[2′,3′:3,4]pyrazolo[1,5-a]-pyrimidine derivative 21 in a good yield. The structures of target molecules were elucidated using elemental analyses and spectral data.     

N-糖基-N'-(6-取代色酮-3-基-亚甲氨基)硫脲类化合物的合成

糖基异硫氰酸酯(1a～1c)与无水肼反应, 生成糖基氨基硫脲2a～2c, 再与6-取代-3-甲酰基色酮3a～3d反应, 得到一系列新的N-糖基-N-(6-取代色酮-3-基-亚甲氨基)硫脲类化合物4a～4d, 5a～5d, 6a～6d. 所有新化合物的结构均经IR, ¹H NMR, MS谱和元素分析证实. 所得糖的衍生物构型保持不变, 均为β-型.     

Synthesis and Biological Activity of a Series of New Thieno[2,3-d]Pyrimidines

Ethyl 2-amino-5-ethylthiophene-3- carboxylate 1, obtained from the reaction of butyraldehyde, ethyl cyanoacetate, sulfur, and triethylamine, reacted with benzoylisothiocyanate to give the corresponding ureido derivatives 2 in a high yield. Further reactions of the compound 2 with an aqueous-alcohol solution of potassium hydroxide and then with hydrochloric acid gave the 2-thio-thieno[2,3-d]pyrimidine-4-ones 3, which were reacted with RX to give novel compounds 4a–4i. Treating the compound 3 with dibromoalkane led to the formation of triacylic compounds 5j–5m. Their structures were clearly verified by IR, ¹H NMR, EI-MS spectroscopy, and elemental analysis. The results of a preliminary bioassay indicated that some compounds possess excellent inhibitory activities against the root and the stalk of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L.

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.     

Regiospecific Synthesis of N-Sulfanilyl Heterocyclic Ketene Aminals

Heterocyclic ketene aminals 1 or 2 reacted with N-acetylsulfanilyl chloride 3 in the presence of sodium hydride to afford N-sulfanilyl heterocyclic ketene aminals 4 or 5 regiospecifically.