Reactions of 2-aryl-4-methoxy-9-oxocyclohepta[b]pyrylium perchlorates with hydroxylamine and hydrazines

2-Aryl-4-methoxy-9-oxocyclohepta[b]pyrylium perchlorates 1a-c reacted with hydroxylamine hydrochloride and hydrazine sulfate in the presence of triethylamine to afford 2-aryl-4,9-dihydrocyclohepta[b]pyran-4,9-dione 4-oximes 3a-c and 4-hydrazones 4a-c in good yields, respectively. On the other hand, the reactions with methylhydrazine and phenylhydrazine gave respectively 1-methyl- and 1-phenyl-substituted 5-aryl-3-(3-tropolonyl)pyrazoles 5a-c and 6a-c in excellent yields. Treatment with 4-nitrophenylhydrazine gave 2-aryl-4,9-dihydrocyclohepta[b]pyran-4,9-dione 4-(4-nitrophenyl)hydrazones 7a-c in good yields.     

Microwave assisted synthesis and unusual coupling of some novel pyrido[3,2-f][1,4]thiazepines

3-Amino-3-thioxopropanamide (1) reacted with ethyl acetoacetate to form 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide (2), which reacted with α-haloketones 3 to produce 2,3-disubstituted-8-hydroxy-6-methyl-2H,5H-pyrido[3,2-f]-[1,4]thiazepin-5-ones 4a-c. Benzoylation of 4c led to the formation of the dibenzoate derivative 9. Compounds 4a-c could be prepared stepwise through the formation of S-alkylated derivatives 10a-c. Compounds 2, 4a-c, 9 and 10a-c were prepared using microwave as a source of heat, and gave better yields in shorter times than those achieved by traditional methods. Coupling of 4a-c with arenediazonium chlorides proceeded unusually to give the 6-hydroxy-4-methyl-2-(arylazo)thieno[2,3-b]pyridin-3(2H)-one ring contraction products 14. Structures of the newly synthesized compounds were proven by spectral and chemical methods.     

5-(2’-羧乙基)-6-烷基-3,4-二氢吡喃酮的合成

吡喃酮是许多天然产物的结构单元,我们曾由4-异丁酰基庚二酸在过量醋酸酐及乙酰氯存在下回流得到7-氧代-8,8-二甲基-△~9-六氢香豆素.本文由二氰乙基-β-二酮进行酮解水解反应得到4-酰基庚二酸1_(a-c)。 在过量醋酸酐、乙酰氯存在下由1_a、1_c为底物进行反应没有得到双环的香豆素衍生物.其产物和单纯以乙酐为缩合剂时的产物2_a、2_c相同,产率分别为68％、63％。2_c可在硫酸铁催化     

Synthesis, reactions and antimicrobial activities of 8-ethoxycoumarin derivatives

Condensation of 3-acetyl-8-ethoxycoumarin (3) with thiosemicarbazide gave ethylidenehydrazinecarbothioamide 5, which was transformed into the thiazolidin-4-one derivatives 6,7. Interaction of 3 with DMF/POCl(3) gave b-chloroacroline derivative 8. Treatment of 3 with malononitrile gave benzo[c]chromone and 2-aminobenzonitrile derivatives 9 and 10, respectively with respect to the reaction conditions. Condensation of 3-(2-bromoacetyl)-8-ethoxycoumarin (4) with o-phenylenediamine gave 3-(quioxaline-2-yl)-8-ethoxycoumarin hydrobromide (11), while 4 reacted with 2-aminopyridine to give chromenopyridopyrimidine derivative 12. Condensation of 4 with potassium thio-cyanate/methanol gave an unexpected derivative, 2H-chromeno-3-carboxy(methyl-carbonimidic)thioanhydride 16, which upon treatment with (NH(2))(2)·H(2)O gave 3-ethoxy-2-hydroxybenzaldehyde azine 19. Interaction of 4 with thiourea derivatives gave thiazole derivatives 20a-c. The structures of the newly synthesized compounds were confirmed by their spectra data. The newly synthesized compounds were also screened for their antimicrobial activity.     

Synthesis and antimicrobial activity of new 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole,thiopyrane, thiazolidinone,and azepine derivatives

4-oxo-4-phenylbutanehydrazide 3 was reacted with aryl or alkyl isothiocyanates to give the corresponding N-substituted-2-(4-oxo-4-phenylbutanoyl) hydrazine-1-carbothioamide 4a-c . Cyclization of thiosemicarbazides 4a-c with sodium hydroxide led to the formation of 3-(4-sub-5-thioxo-1,2,4-triazol-3-yl)-propanone 5a-c . Desulfurization of thiosemicarbazides 4a-c by mercuric oxide afforded 3-(5-(sub-amino)-1,3,4-oxadiazol-2-yl)-propanone 6a-c . The reaction of 4a-c with phosphorus oxychloride gave 3-(5-(sub-amino)-1,3,4-thiadiazol-2-yl)-propanone 7a-c . Treatment of 4a-c with ethyl-bromoacetate or α-bromopropionic acid gave N′-(3-sub-thiazolidin-2-ylidene)-butanehydrazide 8a-c and (N′-(3-sub-oxothiazolidin-2-ylidene)-butanehydrazide 9a-c . Chlorination of oxothiazolidine-hydrazide 9a-c by phosphorus oxychloride afforded N-(3-sub-4-oxothiazolidine)-butane-hydrazonoyl-chloride 10a-c . The reaction of 10a-c with mercaptoacetyl-chloride yielded 2-((4-benzoyl-thiopyrane) hydrazono)-3-sub-thiazolidinone 11a-c . Also, reacted of 10a-c with hydrazine hydrate afforded N″-(3-sub-oxothiazolidine)-butane-hydrazon-hydrazide 12a-c . The 3-sub-2-((pyridazine) hydrazono) thiazolidinone 13a-c was obtained by cyclization of 12a-c via refluxing in DMF. The reaction and cyclized of 9a-c with chloroacetyl-chloride in ethanolic KOH afforded 1-((3-sub-4-oxothiazolidine) amino)-azepine-dione 14a-c . The chemical structures of the new compounds have been confirmed by diverse spectroscopy analyses such as IR, NMR, MS, and elemental analysis. The synthesized compounds were tested for their antimicrobial activity and these compounds were considered (Pyridazin-hydrazono-thiazolidinone 13a-c , oxothiazolidin-azepinedione 14a-c , N-thiazolidin-hydrazon-hydrazide 12a-c , and thiopyran-hydrazono-thiazolidinone 11a-c ) the most effective as antimicrobial activity.     

Synthesis of new thiazolium betaines and the ring expansion reaction via 1,4-dipolar cycloaddition

The 1,4-dipolar cycloaddition of 3-phenyl-7-[N-pheny(carbamoyl)]-5,6-dihydroimidazo[2,1-b]thia-zolium betaine (7d) with a series of aliphatic alkylating agents such as ethyl bromoacetate, α-chloroacetone, and ethyl 4-chloroacetoacetate gave a variety of new ring-expanded cycloadducts 10a-c instead of ring transformation compounds 9 . This result was derived from the difference of reactivity between N- and S-alkylations of thiazolium betaines 7a,d. The advantage of our method is to prepare the triheterocyclic compounds 10a-c of complicated structure using reactive thiazolium betaine 7d in a one-pot without isolation of intermediates. Treatment of N-bridged thiazolo compounds 1a-c with benzoyl isothiocyanate led to new thiazolium betaines 2a-c , which were reacted with methyl iodide to afford the S-alkylated quarternary ammonium salts 3a-c. Synthesis of new 2-iminothiazolinium betaines 5a,b also was carried out.     

The reaction of isothiocyanates with 2-cyanoethanoic acid hydrazide. A novel synthesis of 1,3,4-thiadiazoles

Benzoyl and ethoxycarbonyl isothiocyanates reacted with 2-cyanoethanoic acid hydrazide 2 to afford 1-cyanoacetyl-4-substituted thiosemicarbazide ( 5a,b ). Compound 5a afforded the pyrazolo[1,5-a]-s-triazine derivative 6 on treatment with 5% potassium hydroxide, and cyclised to 2-benzoylamino-5-cyanomethyl-1,3,4-thiadiazole ( 8 ) when boiled under reflux in glacial acetic acid. Compound 8 condensed with aromatic aldehydes to yield the corresponding arylidene derivatives 9a-c . It undergoes coupling with aromatic diazonium salts to afford the hydrazones 11a-c . Similarly, it coupled with diazotised aminopyrazole to afford the cyclic product 12 .     

Synthesis of new pyrazoles,oxadiazoles, triazoles,pyrrolotriazines, and pyrrolotriazepines as potential cytotoxic agents

4-Oxo-4-phenylbutanehydrazide (1) reacted with many active methylene reagents such as acetylacetone, diethylmalonate, ethylacetoacetate, ethylcyanoacetate, benzoyl-acetonitrile, and malononitrile under neat conditions to afford the corresponding pyrazoles (2–7) , also, treatment of butanehydrazide (1) with electrophilic reagents as triethylorthoformate, dimethylformamide-dimethylacetal, acetic anhydride, and carbon disulfide to give 1,3,4-oxadiazoles (8,10,11) and N′-acetyl-butanehydrazide (9) . Reacted of butanehydrazide (1) with potassium thiocyanate gave 1,2,4-triazoles (12) . Similarly, treatment of (1) with chloroacetamide gave 1,2,4-triazinones (13) . The pyrrolotriazinones (14) was obtained by cyclization of (13) . Also, butanehydrazide ( 1 ) was utilized as a starting material for the synthesized of new Schiff bases as N′-(4-sub-benzylidene)-phenylbutane-hydrazide (15a-c) , which are used as an initiative to prepare new compounds such as 1,2,4-triazepinones (16a-c) , pyrrolotriazepinones (17a-c) , 1,2,4-triazines (18a-c) , and pyrrolotriazines (19a-c) by reacted of (15a-c) with each chloroacetamide or formamide. The chemical structure of the newly prepared compounds was determined through the spectrum data, including IR, NMR, and MS. The prepared compounds were tested for their in vitro antitumor activities. The compounds 17a-c , 16a-c , and 19a-c displayed activity against several types of cancer cell lines.     

三种保护的二糖苯丙素苷的合成研究

本文采用先成苷法，从已合成的2-对烯丙氧苯乙基-4,6-O-亚苄基-β-D-葡萄糖苷(1)出发，经2位选择性乙酰化、3位引入三乙酰基保护的鼠李糖基、4，6位脱去亚苄基，得到了关键的中间体4；在化合物4的葡萄糖4、6位分别引入对位取代的肉桂酰基，便得到了保护的二糖苯丙素苷5、7、8。与后成苷法相比，路线缩短一步，收率有所提高。     

Synthesis and analgesic activity of some new pyrazoles and triazoles bearing a 6,8-dibromo-2-methylquinazoline moiety

2-(6,8-Dibromo-2-methylquinazolin-4-yloxy)-acetohydrazide (4) was prepared by the reaction of 6,8-dibromo-2-methylbenzo-[d][1,3]oxazin-4-one with formamide to afford quinazolinone 2, followed by alkylation with ethyl chloroacetate to give the ester 3. Treatment of ester 3 with hydrazine hydrate and benzaldehyde afforded 4 and styryl quinazoline 5. The hydrazide was reacted with triethyl orthoformate, acetylacetone and ethyl acetoacetate and benzaldehyde derivatives to afford the corresponding pyrazoles 6, 7, 9 and hydrazone derivatives 10a-c. Cyclization of hydrazones 10a-c with thioglycolic acid afforded the thiazole derivatives 11a-c. Reaction of the hydrazide with isothiocyanate derivatives afforded hydrazinecarbothioamide derivatives 12a-c, which cyclized to triazole-3-thiols and thiadiazoles 13a-c and 14a-c, respectively. Fusion of the hydrazide with phthalimide afforded the annelated compound 1,2,4-triazolo[3,4-a]isoindol-5-one (15). The newly synthesized compounds were characterized by their spectral (IR, 1H-, 13C-NMR) data. Selected compounds were screened for analgesic activity.     

An efficient synthesis and reactions of novel indolylpyridazinone derivatives with expected biological activity

Reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with indole gave the corresponding butanoic acid 2. Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide gave the pyridazinone derivatives 3a-d. Reaction of 3a with POCl(3) for 30 min gave the chloropyridazine derivative 4a, which was used to prepare the corresponding carbohydrate hydrazone derivatives 5a-d. Reaction of chloropyridazine 4a with some aliphatic or aromatic amines and anthranilic acid gave 6a-f and 7, respectively. When the reaction of the pyridazinone derivative 3a with POCl(3) was carried out for 3 hr an unexpected product 4b was obtained. The structure of 4b was confirmed by its reaction with hydrazine hydrate to give hydrazopyridazine derivative 9, which reacted in turn with acetyl acetone to afford 10. Reaction of 4b with methylamine gave 11, which reacted with methyl iodide to give the trimethylammonium iodide derivative 12. The pyridazinone 3a also reacted with benzene- or 4-toluenesulphonyl chloride to give 13a-b and with aliphatic or aromatic aldehydes to give 14a-g. All proposed structures were supported by IR, (1)H-NMR, (13)C-NMR, and MS spectroscopic data. Some of the new products showed antibacterial activity.     

Synthesis of heierocyclic compounds from 2-phenyl-1, 2,3-triazole-4-formylhydrazine

2-Phenyl-1, 2, 3-triazole-4-formylhydrazine (2) was prepared by hydrazinolysis of the corresponding ester 1. Reaction of 2 with CS2/KOH gave the oxadiazole derivatives (3) which via, Mannich reaction with different dialkyl amines furnished 3-N, N-dialkyl derivatives (4a-c). Also, condensation of 2 with appropriate aromatic acid in POCl3 yielded oxadiazole derivatives (5a-c), or with aldehydes and ketones afforded hydrazones (6a-c). Cyclization of (6a-c) with acetic anhydride gave the desired dihydroxadiazole derivatives (7a-c). On the other hand, reaction of dithiocarbazate (8) with hydrazine hydrate gave the corresponding triazole derivative (9) which on treatment with carboxylic acids in refluxing POCl3 yielded s-triazole[3,4-b]-1, 3, 4-thiadiazole derivatives (10a-b). The structures of all the above compounds were confirmed by means of IR, 1H NMR, MS and elemental analysis.     

Retro-ene reactions in heterocyclic synthesis,III. A new route to 4,5-dihydrooxazoles and 5,6-dihydro-4H-1,3-oxazines

Methyl (E)-4,4-dimethyl-5-oxo-2-pentenoate ( 1 , X = O) reacted with 1,2- or 1,3-aminoalcohols 3 to yield oxazolidines 4a-c or tetrahydro-1,3-oxazines 4d,e. The corresponding imino ester 1 (X = NBu-t) also gave 4 on reaction with 3 . Compounds 4 on heating at 230° yielded 4,5-dihydrooxazoles 5a-c or 5,6-dihydro-4H-1,3-oxazines 5d,e along with methyl 4-methyl-3-pentenoate ( 6 ).     

Mn(III)/Cu(II)-mediated oxidative radical cyclization of alpha-(Methylthio)acetamides leading to erythrinanes

Treatment of N-[2-(3,4-dimethoxyphenyl)ethyl]-alpha-(methylthio)acetamide 3 with Mn(OAc)3 in the presence of Cu(OAc)2 gave tetrahydroindol-2-one 4, which then cyclized with Mn(OAc)3 to give 4-acetoxyerythrinane 5. A similar reaction of the 3,4-methylenedioxyphenyl congener 8 also gave tetrahydroindol-2-one 9, which, however, gave only a trace amount of the Mn(OAc)3-mediated cyclization product 11 and afforded the oxidation product 10. On the basis of these results, formation of 5 from 4 was thought to proceed via nucleophilic attack of the pyrrole ring on the cation-radical lX, generated by a single electron-transfer reaction of the acetoxy-substituted intermediate V. Treatment of compound 16 with Mn(OAc)3/Cu(OAc)2 gave no erythrinane derivative with recovery of the starting material, indicating that the presence of a methylthio group of 4 is essential for effecting the formation of erythrinane 5. On the other hand, treatment of 3 with Mn(OAc)3 using Cu(OTf)2 as an additive in place of Cu(OAc)2 gave another erythrinane 17. This method was applied to a formal synthesis of 3-demethoxyerythratidinone (20), a naturally occurring Erythrina alkaloid.     

Reactions of 3-acetyltropolone with benzaldehydes in trimethyl orthoformate in the presence of perchloric acid: Synthesis of 2-aryl-4-methoxy-9-oxocyclohepta[b]pyrylium perchlorates

3-Acetyltropolone ( 1 ) reacted with benzaldehydes in trimethyl orthoformate in the presence of perchloric acid to afford 2-aryl-4-methoxy-9-oxocyclohepta[b]pyrylium perchlorates 3a-c in 25–37% yields. From the filtrates, 3-(3,4-diaryl-3-butenoyl)tropolones 4a,b and 3-(2-methoxycinnamoyl)tropolone ( 5 ) were also isolated.     

Synthesis and anticancer activity of some novel tetralin-6-yl-pyrazoline, 2-thioxopyrimidine, 2-oxopyridine, 2-thioxo-pyridine and 2-iminopyridine derivatives

The title compounds were prepared by reaction of 6-acetyltetralin (1) with different aromatic aldehydes 2a-c, namely 2,6-dichlorobenzaldehyde, 2,6-diflouro-benzaldehyde, and 3-ethoxy-4-hydroxybenzaldehyde, to yield the corresponding a,b-unsaturated ketones 3a-c. Compound 3b was reacted with hydrazine hydrate to yield the corresponding 2-pyrazoline 4, while compounds 3a,b reacted with thiourea to afford the 2-thioxopyrimidine derivatives 5a,b, respectively. The reaction of 1, and the aromatic aldehydes 2a-c with ethyl cyanoacetate, 2-cyano-thioacetamide or malononitrile in the presence of ammonium acetate yielded the corresponding 2-oxopyridines 6a,b, 2-thioxopyridines 7a-c or 2-iminopyridines 8a,b, respectively. The newly prepared compounds were evaluated for anticancer activity against two human tumor cell lines. Compound 3a showed the highest potency with IC(50) = 3.5 and 4.5 μg/mL against a cervix carcinoma cell line (Hela) and breast carcinoma cell line (MCF7), respectively.     

Bridged tetraquaternary salts from N,N'-polyfluoroalkyl-4,4'-bipyridine

4,4'-Bipyridine (1) with excess of polyfluoroalkyl bromide or iodides 2a-d at 100-110 degrees C without solvent gave the monoquaternary salts 3a-d in >90% yields. However, 1 with 2.5 equiv of 2a-c in DMF at 110 degrees C resulted in the diquaternary salts 5a-c in >85% yields. In DMF, 5a-c were obtained in comparable yields when a molar excess of 2a-c reacted with 3a-c. 1,4-Dibromobutane with 3a,b in DMF at 100 degrees C led to the tetraquaternary salts 7a,b in approximately 85% yields. In water or acetone/water as a solvent, salts 3a-d and 5a-c were metathesized with LiN(SO(2)CF(3))(2) and KSO(3)CF(3) to produce monoquaternary ionic liquids 4a-h in >88% yields and diquaternary ionic liquids 6a-f in >86% yields, respectively. Tetraquaternary ionic liquids 8a,b were obtained when LiN(SO(2)CF(3))(2) was reacted with salts 7a,b. These compounds were stable to 340 degrees C as determined by DSC. They are the first N-mono-, N,N'-di-, and N,N,N',N'-tetra-4,4'-polyfluoroalkylbipyridinium quaternary salts and ionic liquids.     

Polycondensed nitrogen heterocycles. XXII. A new synthesis of 5,6-dihydro-7H-pyrazolo[1,5-d][1,4]benzodiazepin-6-ones

A new synthesis of 2-methyl-9-R'-10-R-5,6-dihydro-7H-pyrazolo[1,5-d][1,4]benzodiazepin-6-ones ( 4a-c ) is deserved. Reaction of ethyl hydrazinoacetate hydrochloride with 1,3-diketones 1a-c gave both 3-methyl-5-(4R'-5-R-2-nitrophenyl)pyrazol-1-yl-acetate acids ( 2a-c ) and the corresponding ethyl esters 3a-c . Reduction with the appropiate reducing agent of compounds 2a-c and 3a-c directly gave the title compounds. Compound 4a showed insecticidal properties against the house fly.     

Synthesis of new 4-amino-5-(1,4-benzodioxan-2-yl)-4<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazole-3-thiol derivatives

Acylation and cyclization reactions of 4-amino-5-(1,4-benzodioxan-2-yl)-4H-1,2,4-triazole-3-thiol were studied. Acylation of the title compound with substituted benzoyl chlorides gave the corresponding amides, whereas its reactions with substituted benzoic acids in the presence of POCl3 were accompanied by cyclization with formation of triazolothiadiazoles containing a 1,4-benzodioxane substituent. 4-Amino-5-(1,4-benzodioxan-2-yl)-4H-1,2,4-triazole-3-thiol reacted with substituted benzaldehydes to afford the corresponding Schiff bases, and its alkylation with chloroacetic acid in ethanol in the presence of sodium acetate gave S-ethoxycarbonylmethyl derivative.     

Synthesis of 3-cyano-2-pyridone derivative and its utility in the synthesis of some heterocyclic compounds with expecting antimicrobial activity

New 2-pyridone derivatives bearing p-methoxyphenyl and p-bromophenyl substituents at C-4 and C-6 were prepared smoothly by the one-pot reaction in high yield, and in a comparatively short time, it reacted with phosphorous oxychloride to produce the corresponding chloro compound. The latter was reacted with several nitrogen nucleophiles such as sodium azide, hydrazine, acetohydrazide, and benzohydrazide to give tetrazolo, hydrazino, and triazolo derivatives, respectively. The reaction of hydrazino derivative with cyclopentanone, furan-2-carbaldehyde afforded the corresponding hydrazone derivatives. Cyclocondensation of the latter compounds with thioglycolic acid afforded the nicotinamide derivatives. 2-Pyridone reacted with ethyl chloroacetate to afford chloroacetate and ethyl acetate derivatives. Ethyl acetate-derivative reacted with hydrazine hydrate and gave the acetohydrazide derivative, it was condensed with p-anisaldehyde and gave the 4-methoxybenzylidene acetohydrazide derivative. Also, 2-pyridone reacted with chloroacetic acid and or benzoyl chloride, afforded the benzoate derivative and 2-((6-(4-bromophenyl)-3-cyano-4-(4-methoxyphenyl) pyridin-2-yl) oxy) acetic acid, respectively. Structures of the products were confirmed using spectroscopic data and elemental analyses. Antibacterial activity of the synthesized compounds was evaluated against Escherichia coli and Staphylococcus aureus.