Synthesis and Antimicrobial Activities of Novel 2‐[substituted‐1H‐pyrazol‐4‐yl] Benzothiazoles,Benzoxazoles, and Benzimidazoles

In an endeavor to find a new class of antimicrobial agents, a series of novel substituted benzimidazole, benzoxazole, and benzothiazole derivatives 6 containing pyrazole moiety have been synthesized by reaction of 3‐aryl‐4‐formyl pyrazole 4 with substituted phenylenediamine or o‐aminophenol or o‐aminothiophenol 5 . Reaction of phenyl hydrazine or 2‐hydrazinopyridine 1 with substituted acetophenones 2 gave the corresponding hydrazones 3 , which on Vilsmeier–Haack reaction with POCl₃–DMF gave substituted 3‐aryl‐4‐formyl pyrazoles 4 . All final compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k were evaluated for in vitro antibacterial activities against Escherichia coli and Staphylococcus aureus strains and in vitro antifungal activity against Candida albicans and Aspergillus niger strains by using serial dilution method. The antimicrobial activities were expressed as the minimum inhibitory concentration in µg/mL. The compound containing benzimidazole and benzoxazole moiety gave better antibacterial and antifungal activities than benzothiazole compounds.     

Utility of (p‐Sulfonamidophenyl)azomalononitrile,and Ethyl Acetoacetate in Synthesis of Fused Azole and Azines Derivatives II

[(p‐Sulfonamidophenyl)azo]malononitrile ( 1a,b ) reacted with N‐cyclohexanemethylidene‐2‐cyanoacetohydrazide, N'‐arylmethylidene‐2‐cyanoacetohydrazide ( 3a‐c ), S‐methylthiourea and hydrazine hydrate to afford [1,2,4]triazolo‐[1,5‐a]pyridinone derivatives ( 2a,b ) & ( 4a‐c ), substituted pyrimidines 5a,b and 6a,b. The corresponding pyridazinones 7a,b were synthesized from the reaction of 1c,d with ethyl cyanoacetate. Compound 7a,b reacted with elemental sulfur to yield 8a,b . Compound 6a underwent cycloaddition with α‐cinnamonitrile 9a‐e to yield 11a‐c, 14 and 15 . Also, compound 6a reacted with β‐ketoester and 1,3‐diketones to give 16, 17 and 18 .     

Synthesis of Pyrano‐ and Pyrido‐Anellated Pyranosides as Precursors for Nucleoside Analogues

The push‐pull activated methyl (3Z)‐4,6‐O‐benzylidene‐3‐[(methylthio)methylene]‐3‐deoxy‐α‐D‐erythro‐hexopyranosid‐2‐ulose (1) reacted with dialkyl malonate in the presence of potassium carbonate to give the alkyl (2R,4aR,6S,10bS)‐4a,6,8,10b‐tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxylates 2 and 3. Treatment of 1 with 3‐oxo‐N‐phenyl‐butyramide, N‐(4‐methoxy‐phenyl)‐3‐oxo‐butyramide, and 3‐oxo‐N‐o‐tolyl‐butyramide, respectively, in the presence of potassium carbonate and 18‐crown‐6 yielded the (2R,4aR,6S,10bS)‐9‐acetyl‐7‐aryl‐4,4a,7,10b‐tetrahydro‐6‐methoxy‐2‐phenyl[1,3]dioxino‐[4′,5′:5,6]pyrano[3,4‐b]pyridin‐8(6H)‐ones 4–6. (2R,4aR,6S,10bS)‐4,4a,8,10b‐Tetrahydro‐6‐methoxy‐8‐oxo‐2‐phenyl‐4H‐pyrano[3′,2′:4,5]pyrano[3,2‐d][1,3]dioxine‐9‐carboxamide (7) was prepared by anellation reactions of 1 either with malononitrile or with cyanoacetamide.     

Synthesis,Characterization, and Cytotoxicity Evaluation of Some New Benzo[f]coumarin Derivatives

Interaction of 2‐(bromoacetyl)‐3H‐benzo[f]coumarin ( 1 ) with salicylaldehyde afforded 2‐(2‐oxo‐2‐(3H‐benzo[f]coumarin‐2‐yl)ethoxy)benzaldehyde ( 2 ) which underwent self‐condensation in refluxing dimethylformamide (DMF) to afford 2‐(2‐benzofuroyl)‐3H‐benzo[f]coumarin (3). Treatment of 1 with o‐aminothiophenol ( 4 ) gave 2‐(2‐((2‐aminophenyl)thio)acetyl)‐3H‐benzo[f]coumarin (5) . Refluxing of 5 in DMF led to formation of 2‐(4H‐[1,4]‐benzothiazin‐3‐yl)‐3H‐benzo[f]coumarin (6). Treatment of 1 with aryl amines 7a–d in boiling DMF gave 1‐aryl‐3‐hydroxybenzo[5,6]chromeno[4,3‐b]pyrrol‐4(1H)‐one ( 10a–d ) . Condensation of 11 with o‐phenylenediamine gave 2‐(2‐methyl‐2,3‐dihydro‐1H‐benzimidazol‐2‐yl)‐3H‐benzo[f]coumarin ( 12 ). Interaction of 2‐acetyl‐3H‐benzo[f]coumarin ( 11 ) with arylidene malonononitrile gave 4‐hydroxy‐2‐(3H‐benzo[f]coumarin‐2‐yl)‐5H‐dibenzo[c,f]chromen‐5‐one ( 16) . All reaction products were characterized by analytical and spectral data. Novel compounds bioactivity as antitumor were examined for in vitro cytotoxicity against HepG‐2 and MCF‐7.     

Synthesis and Antifungal Activities of ω‐[4‐Aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenones

New 4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thiones 3 have been synthesized by the intramolecular cyclization of 4‐aryl‐1‐(1‐phenyl‐5‐methyl‐1,2,4‐triazol‐4‐formyl)thiosemicarbazides 2 with an 8% NaOH solution, and then 3 reacted with ω‐bromo‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenone to afford ω‐[4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)‐acetophenones 4 . The preliminary biological test showed that the representative compounds possess some anti fungal activities.     

Synthesis of Some New Heterocycles Derived from Phenylacetyl Isothiocyanate

Phenylacetyl isothiocyanate (1) was reacted with benzoyl hydrazine (2a) in acetonitrile to give thiosemicarbazide derivative 3 which was cyclized by polyphosphoric acid to give 1,2,4-triazoline-5-thione derivative 4. Treatment of 1 with thiosemicarbazide (2b) yielded another 1,2,4-triazoline-5-thione derivative 5. Similar treatment of 1 with phenyl hydrazine (2c) in acetonitrile gave a differently substituted 1,2,4-triazoline-5-thione derivative 6 in one pot-reaction. On the other hand, when the reaction was carried out in acetone, a mixture of 6 and thiadiazolidine derivative 7 was obtained. However, reaction of 1 with hydrazine hydrate (2d) gave hydrazine derivative 8. Reaction of isothiocyanate 1 with anthranilic acid (9) gave benzo[d][1,3,6]oxazin-1-one derivative 10. Treatment of 1 with 2-aminothiophenol (11a), 2-aminophenol (11b) or o-phenylenediamine (11c) produced benzothiazole derivative 12a, benzoxazole derivative 12b and benzimidazole derivative 12c, respectively. The structures of all the products were confirmed by micro-analytical and spectral data.     

Novel aluminium compounds derived from Schiff bases: Synthesis,characterization and catalytic performance in hydroboration

Seven novel aluminium complexes supported by Schiff base ligands derived from o‐diaminobenzene or o‐aminothiophenol were synthesized and characterized. The reactions of AlMe₃ with L¹ (N,N′‐bis(benzylidine)‐o‐phenylenediamine) and L² (N,N′‐bis(2‐thienylmethylene)‐o‐phenylenediamine) gave the complexes L¹AlMe₃ ( 1 ) and L²AlMe₂ ( 2 ), respectively, which involved two types of reaction mechanisms: one was proton transfer and ring closure, and the other was alkyl transfer. Complexes L³AlMe₂ (HL³ = 4‐chlorobenzylidene‐o‐aminothiophenol) ( 3 ), L⁴AlMe₂ (HL⁴ = 2‐thiophenecarboxaldehyde‐o‐aminothiophenol) ( 4 ), L³AlH(NMe₃) ( 5 ), L⁴AlH(NMe₃) ( 6 ) and L⁵AlH(NMe₃) (HL⁵ = 4‐methylbenzylidene‐o‐aminothiophenol) ( 7 ) were prepared by reacting HL^3–5 with equimolar AlMe₃ or H₃Al?NMe₃, respectively. Compounds 3 – 7 feature an organic–inorganic hybrid containing CNAlSC five‐membered ring. All complexes were characterized using ¹H NMR and ¹³C NMR spectroscopy, X‐ray crystal structure analysis and elemental analysis. The efficient catalytic performances of 1 – 7 for the hydroboration of carbonyl groups were investigated, with compound 4 exhibiting the highest catalytic activity among all the complexes.     

Synthesis of Coumarin Substituted Triazolothiadiazine Derivatives via Ring Transformation Reaction

A novel ring transformation reaction for the synthesis of 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones has been described. Reaction of 3‐(2‐bromoacetyl)coumarins ( 1 ) with 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol ( 2 ) gave ketones ( 4a–h ). The in situ formed ketones ( 4a–h ) were reacted with hydrazine hydrate to give 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones ( 3a–h ) and not 5 or 6 . The compounds ( 3a–h ) can also be prepared by the reaction of 3‐(2‐bromoacetyl)coumarins ( 1 ) with 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol ( 2 ) in anhydrous ethanol to give corresponding 3‐(2‐(5‐aryl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐2H‐chromen‐2‐ones ( 4a–h ). These on reaction with hydrazine hydrate in acetic acid gave corresponding 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones ( 3a–h ).     

Synthesis of new annulated pyridazine derivatives and studying their antioxidant and antimicrobial activities

Benzil was reacted with cyanoacetohydrazide under microwave irradiation to give 3-oxo-5,6-diphenyl-2,3-dihydropyridazine-4-carbonitrile 1 which used as starting material for the synthesis of new heterocyclic compounds. Chlorination of pyridazinone 1 with POCl₃ afforded the chloro-pyridazine derivative 3, which then condensed with 2-aminothiazole or hydrazine hydrate to produce 3,4-diphenyl-5H-thiazolo[3′,2′:1,2]pyrimido[4,5-c]pyridazin-5-one 5 or 3-hydrazinyl-5,6-diphenylpyridazine-4-carbonitrile 6, respectively. New Schiff bases were obtained by condensation reactions of compound 6 with different aldehydes. On the other hand, compound 6 reacted with different carbon electrophiles naming acetyl acetone, diethyl malonate, and phenyl isothiocyanate producing new pyarazolo-pyridazine derivatives 11, 12, and 14, respectively. Chemical structures of all newly synthesized compounds were confirmed on the basis of spectral data and had been screened for antimicrobial and antioxidant activity.     

Synthesis of Novel (3a,S)‐1‐Aryl/aryloxy/alkoxy‐3a,4‐dihydro‐3H‐1λ5‐[1,3,2]oxazaphospholo [3,4‐a] indole‐1‐ones,Thiones, and Selenones

Synthesis of novel (3a,S)‐1‐aryl/aryloxy/alkoxy‐3a,4‐dihydro‐3H‐1λ⁵‐[1,3,2]oxazaphospholo [3,4‐a] indole‐1‐ones, thiones, and selenones was achieved in two steps with high yields from 2,3‐dihydro‐1H‐indol‐2(S)yl methanol (1) and dichlorophenyl phosphine/ethyl dichlorophosphite (2a and b) in the presence of triethylamine in dry THF followed by treatment with hydrogen peroxide, sulfur, and selenium. The compounds 4g–k have been synthesized by the direct cyclocondensation of 1 with different substituted phenyl phosphorodichloridates (2c–e, g) and bis(2‐chloroethyl) phosphoramidic dichloride (2f).     

4-芳基-6-芳氧甲基吗啉-3-酮衍生物的合成及其对A549肺癌细胞生长抑止活性的评价

A series of 4-aryl-6-aryloxymethylmorpholin-3-one derivatives were synthesized very efficiently from readily available starting compounds in two steps. Ring opening reactions of epoxides with aniline compounds on alumina gave corresponding β-aminoalcohols （3）. The resulting β-aminoalcohols were reacted with 2-chloroacetyl chloride to yield the desired 4-aryl-6-aryloxymethylmorpholin-3-one derivatives （5）. All compounds 5 were assayed for inhibitory activity against A549 lung cancer cell growth, and the inhibitory effect of the novel morpholin-3-ones on cell viability was dose-dependent.     

Synthesis and Biological Study of Some 4-oxo-Thiazolidine Derivatives of 2-Aminothiazole

Conventional and microwave assisted synthesis of new series of N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐5‐(substituted benzylidene)‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 5a–5m have been developed. The cycloaddition reaction of thioglycolic acid with N‐{2‐(substituted benzylidenehydrazino)‐ethyl}‐2‐aminothiazole 3a–3m in the presence of anhydrous ZnCl₂ afforded new heterocyclic compounds N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 4a–4m . The later product on treatment with several selected substituted aromatic aldehydes in the presence of C₂H₅ONa undergoes Knoevenagel reaction to yield 5a–5m . The structures of compounds 1 , 2 , 3a–3m , 4a–4m and 5a–5m were confirmed by IR, ¹H NMR, ¹³C NMR, FAB‐Mass and chemical analysis. All above compounds were screened for their antimicrobial activities against some selected bacteria and fungi and antituberculosis study against M. tuberculosis.     

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 and Structure of Novel Thieno[2, 3‐d]Pyrimidine Derivatives Containing 1, 3, 4‐Oxadiazole Moiety

The reaction of 5‐(1‐pyrrolyl)‐4‐methyl‐2‐phenylthieno[2, 3‐d]pyrimidine carbohydrazide 5 with CS₂ in the presence of pyridine afforded the 6‐(2, 3‐dihydro‐2‐mercapto‐1, 3, 4‐oxadiazol‐5‐yl)‐4‐methyl‐5‐(1‐pyrrolyl)‐2‐phenylthieno[2, 3‐d]pyrimidine 6 , which reacted with methyl iodide in the presence of sodium methoxide to yield the 6‐(2‐methylthio‐1, 3, 4‐oxadiazol‐5‐yl)‐4‐methyl‐5‐(1‐pyrrolyl)‐2‐phenyl‐thieno[2, 3‐d]pyrimidine 7. The 6‐(2‐substituted‐1, 3, 4‐oxadiazol‐5‐yl)‐2‐phenylthieno[2, 3‐d]pyrimidine derivatives 9, 11 and 13 were obtained by the condensation of 6‐(2‐methylthio‐1, 3, 4‐oxadiazol‐5‐yl)‐2‐phenylthieno[2, 3‐d]pyrimidine 7 with appropriate secondary amines. The structure of the new compounds was substantiated from their IR, UV‐vis spectroscopy, ¹H NMR, mass spectra, elemental analysis and X‐ray crystal analysis.     

Synthesis of 1‐Amino‐5,6‐diaryl‐3‐cyano‐1H‐pyridin‐2‐ones and 6,7‐Diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines from Isoflavones

The one‐step cyclocondensation of substituted isoflavones (=3‐phenyl‐4H‐1‐benzopyran‐4‐ones) with cyanoacetohydrazide in the presence of KOH afforded a mixture of 1‐amino‐5,6‐diaryl‐3‐cyano‐1H‐2‐pyridin‐2‐ones and 6,7‐diaryl‐4‐cyano‐3‐hydroxy‐1H‐[1,2]diazepines.     

Heterocycles Derived from 5‐(2‐Aminothiazol‐4‐yl)‐8‐hydroxyquinoline: Synthesis and Antimicrobial Activity

5‐(2‐Aminothiazol‐4‐yl)‐8‐hydroxyquinoline 2 has been synthesized by treating thiourea with 5‐chloroacetyl‐8‐hydroxyquinoline 1 . The amine 2 was treated with aromatic aldehydes to furnish schiff bases 6a‐c which on treatment with phenyl isothiocyanate gave the corresponding thiazolo‐s‐triazines 7a‐c . Reaction of 2 with phenyl isothiocyanate gave the corresponding aminocarbothiamide derivative 8 which on reaction with malonic acid in acetyl chloride afforded thiobarbituric acid derivative 9 . Coupling of 9 with diazonium salt gave the phenyl hydrazono derivative 10 . However, reaction of 2 with carbon disulphide and methyl iodide afforded dithiocarbamidate 12 which on treatment with ethylenediamine, o‐aminophenol and/or phenylenediamine gave the aminoazolo derivatives 13–15 , respectively. Other substituted fused thiazolopyrimidines 16–20 have been also prepared by the reaction of 2 with some selected dicarbonyl reagents. The characterisation of synthesized compounds has been done on the basis of elemental analysis, IR, ¹H‐NMR and mass spectral data. All the newly synthesized compounds have been screened for their antimicrobial activities.     

Domino‐Heck Reactions of Carba‐ and Oxabicyclic,Unsaturated Dicarboximides: Synthesis of Aryl‐Substituted,Bridged Perhydroisoindole Derivatives

The C? C coupling of the two bicyclic, unsaturated dicarboximides 5 and 6 with aryl and heteroaryl halides gave, under reductive Heck conditions, the C‐aryl‐N‐phenyl‐substituted oxabicyclic imides 7a – c and 8a – c (Scheme 3). Domino‐Heck C? C coupling reactions of 5, 6 , and 1b with aryl or heteroaryl iodides and phenyl‐ or (trimethylsilyl)acetylene also proved feasible giving 8, 9 , and 10a – c , respectively (Scheme 4). Reduction of 1b with LiAlH₄ (→ 11 ) followed by Heck arylation and reduction of 5 with NaBH₄ (→ 13 ) followed by Heck arylation open a new access to the bridged perhydroisoindole derivatives 12a , b and 14a , b with prospective pharmaceutical activity (Schemes 5 and 6).     

Synthesis of 2,2′‐Bi‐2H‐3,3′‐diaryl‐1,4‐benzothiazines from α,α‐Dibromoacetophenones and o‐Aminothiophenol

Some 2,2′‐bi‐2H‐3,3′‐diaryl‐1,4‐benzothiazines (5a–f) were synthesized from α,α‐dibromoacetophenones and o‐aminothiophenol.     

Synthesis,Pharmacological, and Biological Screening of Novel Derivatives of Benzodiazepines

A series of novel 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine have been synthesized from 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one. 3‐(Substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one was prepared by condensing 2‐acetyl thiophene with various aromatic aldehydes in the presence of 20% NaOH as base. Different 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one on cyclization with o‐phenylenediamine in the presence of NaOH as base resulted in 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine derivatives. The structures of synthesized compounds are confirmed by IR, ¹H NMR, mass spectra, and elemental analysis. All the compounds have been screened for their antimicrobial, analgesic, and anti‐inflammatory activities.     

Enantiopure Trioxadecalin Derived Liquid Crystals: Influence of the Nature of the Phenyl Substituent on the Mesogenic Properties

Reaction of pseudo‐glucal 1 with Grignard reagents derived from 1‐bromo‐4‐(trimethylsilyloxy)benzene, 1‐bromo‐4‐methoxybenzene, 1‐bromo‐4‐methoxymethoxybenzene, 1‐bromo‐4‐dimethylaminobenzene, in the presence of a catalytic amount of NiCl₂(dppe), gives the corresponding unsaturated β‐C‐aryl glycosides 2. Desilylation and hydrogenation of 2 leads to β‐C‐aryl glycosides 4, which can be used as chiral precursor compounds in the synthesis of chiral liquid crystals. Combination of 4 with arylaldehydes leads to compounds 5–7, whereas reaction with p‐alkoxysubstituted phenylboronic acids gives the trioxaboradecalins 8–11. The mesogenic properties of these compounds are strongly influenced by the nature of the substituent on the phenyl ring in the molecule.