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.     

Pyridazine Derivatives and Related Compounds,Part 12: Synthesis of Some Pyridazino [4 ′ ,3 ′ :4,5]thieno[3,2-d]1,2,3-triazines

Abstract

The syntheses of pyridazino[4′,3′:4,5]thieno[3,2?d]-1,2,3-triazinones 2, 3, 6, derivatives of the ring system thieno[2,3-c]pyridazine, have been accomplished by a diazotization reaction. Reaction of triazine 3 with phosphorous oxychloride led to 4-chloro derivative 7 which, on further displacement reactions, gives 4-substituted derivatives. All new compounds were characterized by elemental analyses and spectral data.     

Thieno[2,3-b]pyridine-2-carbohydrazide in Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine,Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine,and Pyrazolyl,Oxadiazolylthieno[2,3-b]pyridine Derivatives

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reacted with cinnamonitrile derivatives 6a, b, triethylorthoformate, formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the corresponding shiff base 7a, b and pyrido[3′,2′;-4,5]thieno[3,2-d]pyrimidine derivatives 10–13 in respective manner. On the other hand, compound 5 also reacted with carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5 reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylacetone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.     

One pot synthesis of ethyl carboxylate and acetyl selenolo[2,3-b]quinoline derivatives and their tetra/pentacyclic systems

Abstract

Ethylcarboxylate and acetyl selenoloquinoline derivatives were prepared in a one pot synthesis via reaction of sodium hydrogen selenide and 2-chloro-3-cyano-4-methylquinoline followed by reactions with ethyl chloroacetate and chloro acetone respectively which used as precursors to synthesize many of tetra and pentacyclic systems. A new series of pyrimido [4′,5′:4,5]selenolo[2,3-b]quinoline, thiazino[2’,3’:4,5]selenolo[2,3-b]quinoline, oxazino[2',3':4,5]selenolo[3,2-b]quinoline, pyrido[2′,3′:4,5]selenolo[2,3-b]quinoline, pyrido[2′,3′:4,5]selenolo[2,3-b]quinoline-2-substituted selenyl and selenolo[2′,3′:5,6]pyrido[2″,3″:4,5]selenolo[2,3-b]quinoline derivatives were prepared. Elemental analysis, IR, ¹H NMR, ¹³ Abdel-Hafez, S. H.; Gobouri, A. A.; Alshanbari, N. A.; Gad El-Rab, S. M. F. Synthesis of Novel Vitamin E Containing Sulfa Drug Derivatives and Study Their Anti-Bacterial Activity. Med. Chem. Res. 2018, 27, 2341–2352. DOI: 10.1007/s00044-018-2240-7.[Crossref], [Web of Science ®] , [Google Scholar]C NMR and mass spectra confirmed the structures of the newly synthesized compounds.     

2-[4-(2-Thienyl)-1,3-thiazol-2-yl]ethanenitrile in Heterocyclic Synthesis of Biological Interist

Abstract

Thiazolylacetonitrile was used in the synthesis of coumarin, pyrazolo[4,3]pyrimidines, 1,3,4-thiadiazolines, aminothiophenes, and thiazoles in a good yields. Also, pyrazolo[4,5-d]triazolino[4,5-a]pyrimidines, pyrazolo[4,5-d]thiazolino[3,2-a]pyrimidines, and pyrazolo[4,5-d]tetrazolino[1,5-a]pyrimidines were synthesized from pyrazolo[4,5-d]pyrimidine. Structures of the newly synthesized were elucidated by elemental analysis, spectral data, and alternative synthesis routes whenever possible. Some synthesized compounds were tested for their antimicrobial activity.     

Synthesis of Some New Imidazo[4,5-B]Pyridine Derivatives Using 2-Cyanomethyl-1-Methyl-1H-Imidazo[4,5-B]Pyridine

Abstract

The reactions of 2-cyanomethyl-1-methyl-1H-imidazo[4,5-b]pyridine with isothiocyanates, nitroso compounds, acid chlorides, and thioglycolic acid were investigated. New imidazo[4,5-b]pyridine derivatives with various substituents in 2-position and derivatives of the new pyrrolo[2′,1′:2,3]imidazo[4,5-b]pyridine ring system were synthesized. The compounds obtained were tested in vitro for their tuberculostatic activity.     

Pyrimidinthiones (Part I): Utility of 2-Thioxopyrimidin-6-(1H)ones as Ring Transformer in the Synthesis of Fused Bi- and Tri-Cyclic Heterocyclic Compounds and Their Potential Biological Activities

The pyrimidinethiones have wide biological and pharmaceutical activities, that have attracted considerable interest in recent years especially as antiviral inhibiting production of hepatitis B virus (HBV), and in vitro insulin-mimetic. Activity of the complexes of pyrimidinone derivatives evaluated from 50% inhibitory concentration promoted us to study the transformation of the 2-thioxopyrimidin-6(1H) ones to fused bi- and tri-cyclic heterocyclic compounds having the pyrimidine moieties and screening their biological activity.

The reactivity of 2-mercapto-4-aryl-5-cyanopyrimidin-6(1H)ones (1) towards alkylation by different mono and bifunctional halo-organic compounds has been investigated to give S-monoalkylated products 2, 7 and 9; S- and N-dialkylated products 3, 13 and 14. Treatment of 1 and/or 2 with hydrazine hydrate as a nitrogen nucleophile have been investigated to give 4, treatment of 4 with CS₂ and sodium nitrite in the presence of acetic acid (0°C) produced 1,2,4-triazolopyrimidin-5(1H)one derivatives (5)and tetrazolo[1,5-a]pyrimidin-5(1H)ones (6), respectively. Also cyclization of 7 and 9 gave [1,3]thiazolo[3,2-a]pyrimidin-5(1H)one and [1,3]thiazolo[3,2-a]pyrimidin-3,5-dione derivatives 8 and 10 respectively, treatment of 10 with aromatic aldehyde produces 11 which reacted with guanidine HCl to give pyrimido[4,5-d]thiazolo[3,2-a]pyrimidin-6(1H)one derivative 12. Reaction of 14 with o-phenylenediamine was investigated and gave [1,4]quinoxalino[2,3-b][1,3]thiazolo[3,2-a]pyrimidin-9(1H)one derivative 15.     

Reaction of 4-Nitrobenzenesulfenamide with Liquid Ammonia

Abstract

Although numerous investigations on the chemistry of organic sulfenamides, for example, studies on the S–N torsional barrier,¹ the electronic nature of the S–N bond² and some nucleophilic substitutions on sulfur or nitrogen atom³ have been known, no example of nucleophilic substitution on arylcarbon of aromatic sulfenamides has been reported.     

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.     

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.     

Synthesis and Crystal Structure of 2-(4''-Methylphenoxy)-5,8,9-trimethyl-3-phenyl Thieno[3'',2'':5,6]pyrido[4,3-d]pyrimidin-4-(3H)-one Hydrochloride

The title compound 2-(4′-methylphenoxy)-5,8,9-trimethyl-3-phenyl thieno[3′,2′:5,6]pyrido[4,3-d]pyrimidin-4(3H)-one hydrochloride (C26H23Cl4N3O2S, Mr = 583.33) has been deter- mined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21/c with a = 14.8442(11), b = 11.5131(8), c = 17.2010(13) (A), β = 113.7250(10)o, V = 2691.3(3) (A)3, Z = 4, Dc = 1.440 g/cm3, S = 1.094, μ = 0.547 mm-1, F(000) = 1200, the final R = 0.0571 and wR = 0.1458. X-ray analysis reveals that the title compound combines with a molecule of dichloromethane by an intramolecular hydrogen bond. The thienopyridine ring is almost coplanar, and the dihedral angle between the thiophene plane and the pyridine plane is 0.6o.     

Synthesis,Reactions, and Characterization of 6-Amino-4-(Benzo[b]Thiophen-2-YL)-2-Thioxo-1, 2-Dihydropyridine-3, 5-Dicarbonitrile

Abstract

Benzothiophene -2- carbaldehyde 1 reacted with 2-cyanoethanethioamide 2 in 1:2 molar ratios to give the corresponding 6-amino-4-(benzo[b]thiophen-2-yl)-2-thioxo-1, 2-dihydropyridine-3,5-dicarbonitrile 6. The synthetic potentiality of compound 6 was investigated via its reaction with active halogen-containing reagents to afford the corresponding thieno[2,3-b]pyridine derivatives 11a,b, 14, 16, and 19. Also, compound 6 reacted with hydrazine hydrate to give the pyrazolo[3,4-b]pyridine derivative 21. Compound 21 condensed with 4-(2-thienyl)benzaldehyde to afford pyrazolo[3,4-b]pyridine derivative 23. Structural elucidation of all the newly synthesized heterocyclic compounds was based on elemental analyses, IR, ¹H NMR, and mass spectra.

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.     

Zur Reaktion von 4-Alkylaminodihydro-2(1H)-pyridinthionen bzw. -onen mit Ethylmalonsäure-bis-trichlorphenylester

4-Alkylamino-2(1H)-pyridinethiones (1) react with bis-trichlorphenylethylmalonate (3) to give four isomeric products: 5-thioxo-1,6-naphthyridine-2(1H)-ones (4), 7,7-dimethyl-4H-thiopyrano[2,3-b]pyridine-4-ones (6), 2,2-dimethyl-2H-thiopyrano[2,3-b]pyridine-5,7-dioles (7) and 2,2-dimethyl-2H-thiopyrano[2,3-b]pyridine-5(3H)-ones (8). On treatment with alkali the thioxogroup of4 is hydrolyzed and 1,6-naphthyridinediones (5) are formed. Compound5 can also be synthesized by heating the alkylaminopyridones (2) together with3.6 can be hydrolyzed to 2-thioxo-3-pyridylpropylketones (12). On treatment with diluted alkali or conc. acid the aminogroup of7 and8 is hydrolyzed and10 is formed. By heating in 20% NaOH10 is transformed to the dihydroxymercapto-3-pyridylmethylketone (11).

Herrn Prof. Dr.Erich Ziegler mit den besten Wünschen zum 70. Geburtstag gewidmet.     

Evaluation of Neurotropic Activity and Molecular Docking Study of New Derivatives of pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidines on the Basis of pyrano[3,4-c]pyridines

Background: Heterocyclic compounds and their fused analogs, which contain pharmacophore fragments such as pyridine, thiophene and pyrimidine rings, are of great interest due to their broad spectrum of biological activity. Chemical compounds containing two or more pharmacophore groups due to additional interactions with active receptor centers usually enhance biological activity and can even lead to a new type of activity. The search for new effective neurotropic drugs in the series of derivatives of heterocycles containing pharmacophore groups in organic, bioorganic and medical chemistry is a serious problem. Methods: Modern methodology of drugs involves synthesis, physicochemical study, molecular modeling and selection of active compounds through virtual screening and experimental evaluation of the biological activity of new chimeric compounds with pharmacophore fragments. For the synthesis of new compounds, classical organic methods were used and developed. For the evaluation of neurotropic activity of new synthesized compounds, some biological methods were used according to indicators characterizing anticonvulsant, sedative and antianxiety activity as well as side effects. For docking analysis, various soft ware packages and methods were used. Results: As a result of multistep reactions, 11 new, tri- and tetracyclic heterocyclic systems were obtained. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures as well as some psychotropic effects. The biological assays evidenced that nine of the eleven studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of the compounds is low, and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity, it was found that the selected compounds have an activating behavior and anxiolytic effects on the “open field” and “elevated plus maze” (EPM) models. The data obtained indicate the anxiolytic (antianxiety) activity of the derivatives of tricyclic thieno[2,3-b]pyridines and tetracyclic pyridothieno[3,2-d]pyrimidin-8-ones, especially pronounced in compounds 3b–f and 4e. The studied compounds increase the latent time of first immobilization on the “forced swimming” (FS) model and exhibit antidepressant effects; compounds 3e and 3f especially exhibit these effects, similarly to diazepam. Docking studies revealed that compounds 3c and 4b bound tightly in the active site of γ-aminobutyric acid type A (GABA_A) receptors with a value of the scoring function that estimates free energy of binding (∆G) at −10.0 ± 5 kcal/mol. Compound 4e showed the best affinity ((∆G) at −11.0 ± 0.54 kcal/mol) and seems to be an inhibitor of serotonin (SERT) transporter. Compounds 3c–f and 4e practically bound with the groove of T4L of 5HT_1A and blocked it completely, while the best affinity observed was in compound 3f ((∆G) at −9.3 ± 0.46 kcal/mol). Conclusions: The selected compounds have an anticonvulsant, activating behavior and anxiolytic effects and at the same time exhibit antidepressant effects.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis of New 2-[(Substituted-pyrazol-1-yl)carbonyl]-thieno[2,3b]pyridine Derivatives Using 1,3-Diketones,Alkylethoxymethylenes and Ketene Dithioacetals

The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide ( 1 ) with appropriate 1,3-diketones 2a-2d in glacial acetic acid afforded 3-amino-2-[(3,5-disubstituted-pyrazo)-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 3a-3d. 3-Amino-2-[(5-amino-3,4-disubstituted-pyrazol-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 5a-5h were also prepared by treatment of carbohydrazide 1 with appropriate alkylethoxymethylenes and ketene dithioacetals 4a-4h , respectively.     

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 New 3-(3,5-Diamino-1-substituted-pyrazol-4-yl)azo-thieno[2,3-b]pyridines and 3-(2-Amino-5,7-disubstituted-pyrazolo[1,5-a]pyrimidine-3-yl)azothieno[2,3-b]pyridines

Coupling the diazonium salt of 3-amino-2-cyano-4,6-dimethylthieno[2,3-b]pyridine 1 with malononitrile 2 gave 2-cyano-3-(hydrazonomalononitrile)-4,6-dimethylthieno[2,3-b]pyridine 3 which then reacted with hydrazine compounds 4a-4h to yield corresponding 2-cyano-3-(3,5-diamino-1-substituted-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 5a-5h. The 2-cyano-3-(2-amino-5,7-disubstituted-pyrazolo-[1,5-a]pyrimidine-3-yl)azo-4,6-dimethylthieno[2,3-b]pyridines 7a-7f were obtained in good yield by the cyclocondensation reaction of 2-cyano-3-(3,5-diamino-pyrazol-4-yl)azo-4,6-dimethylthieno[2,3-b]pyridine 5a with the appropriate 1,3-diketones 6a-6f under acidic condition.     

2,3-Dihydro-5,6-tetramethylenespiro(cyclohexane-2-thieno[2,3-d]pyrimidine)-4(1H)-thione. A Novel Synthetic Route and Crystalline Structure

Self-condensation of cyclohexylidenecyanothioacetamide gave 2,3-dihydro-5,6-tetramethylenespiro(cyclohexane-2-thieno[2,3-d]pyrimidine)-4(1H)-thione, the structure of which was proved by X-ray analysis. A mechanism is proposed for its formation and its alkylation has been studied.     

Cyanothioacetamide in Heterocyclic Chemistry: Synthesis of Piperidine-3-carbonitrile,Pyrazolopyridine, Thiinopyridine-3-carbonitrile Derivatives,and Their Theoretical Calculations

Cyanothioacetamide ( 1 ) reacted with acrylonitrile ( 2 ) to afford the corresponding 6-oxo-2-sulfanylpiperidine-3-carbonitrile ( 6 ), which oxidized to give compounds 7 and 8 under different conditions. Moreover, compound 6 was used as a starting material to synthesize 12a-c , 16a-d , 26a-c , 27a-c , and 30a-c via reactions with aromatic aldehydes 9a-c , diazonium chlorides 13a-d , and 3-arylpropennitrile derivatives 18a-i respectively. Considering the data of IR, 1 H NMR, mass spectra, elemental analyses, and theoretical calculations, all the structures of the newly synthesized heterocyclic compounds were elucidated.