Reaction of N-(4-Pyridylrnethyl)benzamide N-oxides and N-[(α-acetoxy)-4-pyridylmethyl]benzamides with 1,3-diphenyl-1,3-propanedione

Reaction of N-(4-pyridylmethyl)benzamide N-oxides 2 with 1,3-diphenyl-1,3-propanedione in the presence of acetic anhydride afforded 1,1-dibenzoyl-2-(4-pyridyl)-2-(benzoylamino)ethanes 4 in low yield. Treatment of N-[(α-acetoxy)4-pyridylmethyl]benzamides 3 with 1,3-diphenyl-1,3-propanedione in the presence of triethylamine and chloroform as a solvent provided 4 in high yield. Reaction of 4 with nucleophiles as hydrazine, methyl and phenylhydrazine gave the corresponding pyrazoles 5 .     

Reactions of 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones with arylamines and hydrazine hydrate

Depending on the reaction condition, 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones reacted with aromatic amines to yield 3-arylamino-3-pyrrolin-2-ones or 4-[aryl (arylamino) methylene]tetrahydropyrrole-2,3-diones. Reactions of 1-(4-aminosulfonylphenyl)-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones with hydrazine hydrate afforded pyrrolo[3,4-c]pyrazol-6-ones.     

A new synthesis of novel 1-aryl-3-heteroaryl-1H-pyrazolo[3,4-b]quinoxalines via a Key Intermediate

The chlorination of the α-hydrazonoester 4 with phosphoryl chloride/pyridine gave 3-[α-(o-chlorophenylhydrazono)methoxycarbonylmethyl]-2-chloroquinoxaline 5 , whose cyclization with 1,8-diazabicyclo[5,4,0]-7-undecene afforded 3-methoxycarbonyl-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 6 . The reaction of 6 with hydrazine hydrate provided 3-hydrazinocarbonyl-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 7 , whose reactions with methyl and allyl isothiocyanates furnished 3-(2,3-dihydro-4-methyl-3-thioxo-4H-1,2,4-triazol-5-yl)-1-(o-chlorophenyl)-1H-pyrazolo[3,4-b]quinoxaline 2 and 3-(4-allyl-2,3-dihydro-3-thioxo-4H-1,2,4-triazol-5-yl)-1-(o-chloropheny)-1H-pyrazolo[3,4-b]quinoxaline 8 , respectively. Moreover, the reactions of 7 with triethyl orthoformate and orthoacetate gave 1-(o-chlorophenyl)-3-(1,3,4-oxadiazol-5-yl)-1H-pyrazolo-[3,4-b]quinoxaline 9a and 1(o-chlorophenyl)-3-(2-methyl-1,3,4-oxadiazol-5-yl)-1H-pyrazolo[3,4-b]quinoxaline 9b , respectively.     

Synthesis of pyridazino[4,5-b]indole derivatives from 2-(3-carboxy-1-methylindole)acetic acid anhydride

2-(3-Carboxy-1-methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α-hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2-aryl-4-carbohydrazido-5-methyl-1-oxo-1,2-dihydro-5H/-pyridazino[4,5-b]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2-(3-carboxy-1-methylindole)aceta-mide 5 or the respective 2-aryl-4-carboxamido-5-methyl-5H-pyridazino[4,5-b]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4-chlorophenyl) with 5% sodium hydroxide gave (80%) 2-(3-carboxy-1-methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2-(3-carboxy-1-methylindolyl)-2-(4-chlorophenylhydrazono)acetic acid ( 8 ).     

Thiourea Derivatives,Simple in Structure but Efficient Enzyme Inhibitors and Mercury Sensors

In this study six unsymmetrical thiourea derivatives, 1-isobutyl-3-cyclohexylthiourea (1), 1-tert-butyl-3-cyclohexylthiourea (2), 1-(3-chlorophenyl)-3-cyclohexylthiourea (3), 1-(1,1-dibutyl)-3-phenylthiourea (4), 1-(2-chlorophenyl)-3-phenylthiourea (5) and 1-(4-chlorophenyl)-3-phenylthiourea (6) were obtained in the laboratory under aerobic conditions. Compounds 3 and 4 are crystalline and their structure was determined for their single crystal. Compounds 3 is monoclinic system with space group P2₁/n while compound 4 is trigonal, space group R³:H. Compounds (1–6) were tested for their anti-cholinesterase activity against acetylcholinesterase and butyrylcholinesterase (hereafter abbreviated as, AChE and BChE, respectively). Potentials (all compounds) as sensing probes for determination of deadly toxic metal (mercury) using spectrofluorimetric technique were also investigated. Compound 3 exhibited better enzyme inhibition IC₅₀ values of 50, and 60 µg/mL against AChE and BChE with docking score of −10.01, and −8.04 kJ/mol, respectively. The compound also showed moderate sensitivity during fluorescence studies.     

Synthesis and reactions of 4-(arylhydrazino)coumarins

The interaction of 4-hydroxycoumarin with phenyl-, 2-chlorophenyl- and 4-bromophenyhydrazine hydrochlorides in the presence of triethylamine led in all cases to the corresponding 4-(arylhydrazino)-coumarins and 1-aryl-3-(2-hydroxyphenyl)-2H-pyrazolin-5-ones. 4-(Arylhydrazino)coumarins reacted with 4-chlorobenzaldehyde in the presence of piperidine acetate to give the corresponding 2-aryl-3-(4-chlorophenyl)[1]benzopyrano[4,3-b]pyrazol-4-ones. The reaction of 4-(4-bromophenylhydrazino)-coumarin with 4-chlorobenzaldehyde in the presence of piperidine acetate and an excess of piperidine gave 2-(4-bromophenyl)-5-(4-chlorophenyl)-3-(2-hydroxyphenyl)-4-(piperidinocarbonyl)pyrazole, but the reaction of phenyl- and 4-(2-chlorophenylhydrazino)coumarins with 4-chlorobenzaldehyde gave 1-aryl-5-(4-chlorophenyl)-3-(2-hydroxyphenyl)-4-(1-piperidino)carbonyl-4,5-dihydropyrazoles.     

Manganese(III)-mediated intermolecular cyclization reactions of alkenes and active methylene compounds

The reactions of 1,1-diphenylethene, 1,1-bis(4-chlorophenyl)ethene, 1,1-bis(4-methylphenyl)ethene, and 1,1-bis(4-methoxyphenyl)ethene with 3,5-diacetyl-2,6-heptanedione in the presence of manganese(III) acetate in acetic acid at 80° yielded 4,6-diacetyl-8,8-diaryl-1,3-dimethyl-2,9-dioxabicyclo[4.3.0]non-3-enes (41-48%), 5-acetyl-2,2-diaryl-6-methyl-2,3-dihydrobenzo[b]furans (20–21%), 3-acetyl-5,5-diaryl-2-methyl-4,5-dihydrofurans (5–10%), and benzophenones (3–7%). Similarly, the reactions of 1,1-diarylethenes with dimethyl 2,4-diacetyl-1,5-pentanedioate or diethyl 2,4-diacetyl-1,5-pentanedioate gave the corresponding 4,6-bis(alkoxycarbonyl)-8,8-diaryl-1,3-dimethyl-2,9-dioxabicyclo[4.3.0]non-3-enes in moderate yields.     

Reactions of zinc enolates derived from 1-aryl-2-bromo-alkanones and 1-aryl-2-bromo-2-phenylethanone with 3-aroyl-6-bromochromen-2-ones and 2-benzoylbenzo[f]chromen-3-one

3-Aroyl-6-bromochromen-2-ones and 2-benzoylbenzo[f]chromen-3-one reacted with zinc enolates derived from 1-aryl-2-bromoalkanones and 1-aryl-2-bromo-2-phenylethanone to give, respectively, 4-(1-alkyl-2-aryl-2-oxoethyl)-3-aroyl-6-bromochroman-2-ones and 1-(2-aroyl-1-methyl-2-oxoethyl)-2-benzoyl-1,2-dihydrobenzo[f]chromen-3-ones as a single stereoisomer. Treatment with acetic anhydride of the intermediate product obtained from 3-benzoyl-6-bromochromen-2-one and [1-(4-chlorophenyl)-2-phenylethen-1-yloxy]-zinc(II) bromide resulted in the formation of 3-(1-acetoxy-1-phenylmethylidene)-6-bromo-4-[2-(4-chlorophenyl)-2-oxo-1-phenylethyl]chroman-2-one.     

4,5-Dihydropyrazolo[3,4-f]quinazolines

By reaction of 6-dimethylamino-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinazoline with hydrazine, phenylhydrazine, 4-bromo-, 4-chlorophenylhydrazines, and also reaction of 6-dimethylaminomethylene-5-oxo-2-(4-pyridyl)-5,6,7,8-tetrahydroquinazoline with hydrazine, 4-methoxy- and 2-carboxyphenylhydrazines, we have obtained the corresponding 7-phenyl(4-pyridyl)-substituted 1H(2H)- or 1-aryl-4,5-dihydropyrazolo[3,4-f]quinazolines. Methylation of 7-phenyl-4,5-dihydro-1(2H)-pyrazolo[3,4-f]quinazoline by methyl iodide led to its 2-methyl derivative.     

Synthesis and Crystal Structure of N—tert—butyl—N′—（2，4—dichlorobenzoyl）—N—[1—（4—chlorophenyl）—1,4—dihydro—6—methylpyridazine—4—oxo—3—carbonyl]hydrazine

1 INTRODUCTIONPyridazinone derivatives represent one of the most active classes of compounds possessing a wide spectra of biological activity. They are widely used in pharmaceuticals and agrochemicals[1,2]. Rohm- Haas Company had reported that N-tert-butyl- dibenzoylhydrazine exhibits excellent insecti- cides[3, 4] and t-butyl plays an important role in the insecticide activity [5]. In the previous paper, we had reported that 1-aryl-1,4-dihydro-3- acylhydrazino- carbonyl-4-one-6-methylpy…     

β-三氯锗基丙酸及β-三苯锗基丙酸与苯基溴化镁的反应

三氯锗基丙酸(1a)和三苯锗基丙酸(2a)与过量苯基溴化镁起反应时,这两个分子中的羧基表现出一些奇特性质。当1a和2a与不同浓度的苯基溴化镁起反应时,都能生成相应的酮(3a)和醇(4a)。在稀盐酸作用下,4a极易脱水生成1,1-二苯基-3-三苯锗基丙烯-1(5a)。当1a与苯基溴化镁起反应,然后再用稀盐酸处理也同样得到5a。5a的Ge-C键能被LiAlH~4高选择性地切断,生成三苯基锗烷(6a)和1,1-二苯基丙烯(6b)。     

Reaction of azulene with 1,2-bis[4-(dimethylamino)phenyl]-1,2-ethanediol in a mixed solvent of methanol and acetonitrile in the presence of hydrochloric acid: a facile one-pot synthesis and properties of new triarylethylenes possessing an azulen-1-yl group

Reaction of azulene (1) with 1,2-bis[4-(dimethylamino)phenyl]-1,2-ethanediol (2) in a mixed solvent of methanol and acetonitrile in the presence of 36% hydrochloric acid at 60 °C for 3 h gives 2-(azulen-1-yl)-1,1-bis[4-(dimethylamino)phenyl]ethylene (3) (8% yield), 1-(azulen-1-yl)-(E)-1,2-bis[4-(dimethylamino)phenyl]ethylene (4) (28% yield), and 1,3-bis{2,2-bis[4-(dimethylamino)phenyl]ethenyl}azulene (5) (9% yield). Besides the above products, this reaction affords 1,1-di(azulen-1-yl)-2,2-bis[4-(dimethylamino)phenyl]ethane (6) (15% yield), a meso form (1R,2S)-1,2-di(azulen-1-yl)-1,2-bis[4-(dimethylamino)phenyl]ethane (7) (6% yield), and the two enantiomeric forms (1R,2R)- and (1S,2S)-1,2-di(azulen-1-yl)-1,2-bis[4-(dimethylamino)phenyl]ethanes (8) (6% yield). Furthermore, addition reaction of 3 with 1 under the same reaction conditions as the above provides 6, in 46% yield, which upon oxidation with DDQ (=2,3-dichloro-5,6-dicyano-1,4-benzoquinone) in dichloromethane at 25 °C for 24 h yields 1,1-di(azulen-1-yl)-2,2-bis[4-(dimethylamino)phenyl]ethylene (9) in 48% yield. Interestingly, reaction of 1,1-bis[4-(dimethylamino)phenyl]-2-(3-guaiazulenyl)ethylene (11) with 1 in a mixed solvent of methanol and acetonitrile in the presence of 36% hydrochloric acid at 60 °C for 3 h gives guaiazulene (10) and 3, owing to the replacement of a guaiazulen-3-yl group by an azulen-1-yl group, in 91 and 46% yields together with 5 (19% yield) and 6 (13% yield). Similarly, reactions of 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (12) and 1,1-bis{4-[2-(dimethylamino)ethoxy]phenyl}-2-(3-guaiazulenyl)ethylene (13) with 1 under the same reaction conditions as the above provide 10, 2-(azulen-1-yl)-1,1-bis(4-methoxyphenyl)ethylene (16), and 1,3-bis[2,2-bis(4-methoxyphenyl)ethenyl]azulene (17) (93, 34, and 19% yields) from 12 and 10 and 2-(azulen-1-yl)-1,1-bis{4-[2-(dimethylamino)ethoxy]phenyl}ethylene (18) (97 and 58% yields) from 13.     

Synthesis and Synthetic Application of Phosphonoketene Dithioacetals. New Synthesis of Dithioallenes and (alpha-Dithiocarboxyvinyl)phosphonates

Phosphonoketene dithioacetals 3a-e were obtained in good yields by the reaction of ethyl phosphonoacetates 1a,b with 2-4 equiv of thiols 2a-c in the presence of an alkylaluminum dichloride or dialkylaluminum chlorides. Reaction of 2,2-dithio-1-phosphonovinyl anions with aldehydes afforded allylic alcohols 4-7, 11-18 in good to moderate yields. Treatment of the alcohols 4-6 with t-BuOK in THF led to symmetrical [2 + 2] cycloadducts 20-22 of 1,1-(ethylenedithio)allenes in moderate yields, while a similar reaction of the alcohols 11-13 produced a mixture of symmetrical and unsymmetrical [2 + 2] cycloadducts of 1,1-(trimethylenedithio)allenes,23a-25a and 23b-25b, in 55-94% yields. The alcohol 15 on a similar treatment gave 3-tert-butyl-1,1-bis(ethylthio)allene (26) in quantitative yield. The structures of 20 and 23b were determined by X-ray analysis. Treatment of the alcohols 15 and 18 with trifluoromethanesulfonic acid/n-Bu(4)NX (X = Br, I) or triphenylphosphine/CBr(4) in CH(2)Cl(2) afforded alpha-phosphonodithioacryclic acid esters 34 and 35 in 25-52% yields. The tandem Michael-Wittig reaction of 35 with sodium salt of 2-pyrrolecarbaldehyde in DMF gave ethyl 3-phenyl-3H-cyclopenta[a]pyrrole-2-dithiocarboxylate (36) in 25% yield.     

Synthesis of podands modified with thiosemicarbazide and fluoroalkyl(hydroxy)pyrazoline fragments

1,8-Bis(diisothiosemicarbazido)-3,6-dioxaoctane have been synthesized by subsequent treatment of 2,2′-(ethylenedioxy)bisethylamine with carbon disulfide, sodium chloroacetate, and hydrazine hydrate. 1,8-Bis- (diisothiosemicarbazido)-3,6-dioxaoctane has reacted with lithium 1,1-difluoropenta-2,4-dionate in glacial acetic acid to yield 1,8-bis[5R*,5′R*(5-hydroxy-5-difluoromethyl-4,5-dihydro-3-methyl-1H-pyrazol-1-yl)-1-carbothioamido]-3,6-dioxaoctane. The molecular and crystal structure of the product has been determined by X-ray diffraction analysis.     

Synthesis and some transformations of methyl [4-(oxoacetyl)phenyl]carbamate

The oxidation of methyl (4-acetylphenyl)carbamate with selenium dioxide in dioxane–water (30: 1) gave methyl [4-(oxoacetyl)phenyl]carbamate whose condensation with ethyl acetoacetate or diethyl malonate and hydrazine hydrate afforded ethyl 3-methyl-6-[4-(methoxycarbonylamino)phenyl]pyridazine-4-carboxylate and methyl {4-[5-(hydrazinecarbonyl)-6-oxo-1,6-dihydropyridazin-3-yl]phenyl}carbamate, respectively. The reaction of methyl [4-(oxoacetyl)phenyl]carbamate with o-phenylenediamine in dimethylformamide–ethanol on heating led to the formation of methyl [4-(quinoxalin-2-yl)phenyl]carbamate. Methyl {4-(5,7-dioxo- 4,4a,5,6,7,8-hexahydropyrimido[4,5-c]pyridazin-3-yl)phenyl}carbamate and methyl {4-(5-oxo-7-sulfanylidene- 4,4a,5,6,7,8-hexahydropyrimido[4,5-c]pyridazin-3-yl)phenyl}carbamate were synthesized by reactions of methyl [4-(oxoacetyl)phenyl]carbamate with barbituric and thiobarbituric acids, respectively, and hydrazine hydrate in the presence of zirconyl chloride octahydrate at room temperature.     

Reactions of 5,8-dichloro-2,3-dicyanoquinoxaline with amines and hydrazines. A new and efficient synthetic approach to 3-amino-5,8-dichloroflavazoles

Reactions of 5,8-dichloro-2,3-dicyanoquinoxaline with primary amines and hydrazines under different experimental conditions were investigated. Alkylamines provided novel 3-alkylamino-5,8-dichloro-2-cyanoquinoxalines and N-alkyl-(5,8-dichloro-3-alkylamino-2-quinoxalinyl)carboxamidines in high yields. Alkylhydrazines and lithium arylhydrazinides gave previously unattainable 1-alkyl-3-amino-5,8-dichloroflavazoles and 3-amino-1-aryl-5,8-dichloroflavazoles in good to near quantitative yields whose molecular structure was confirmed by X-ray crystallography of 3-[N,N-bis(4-chlorobenzoyl)amino]-5,8-dichloro-1-phenylflavazole. Reaction with hydrazine gave 5,8-dichloro-3-hydrazino-2-quinoxalinylcarboxamidrazone quantitatively, which was converted to the parent compound of this class of flavazoles, 3-amino-5,8-dichloroflavazole, in high yield by a pyrolytic process involving loss of hydrazine.     

Synthesis of glyco-1-ynitols via 1,1-dibromo-1-alkenes from partially and unprotected aldoses

We report the synthesis of 1,1-dibromo-1-alkenes from partially and unprotected aldoses and the synthesis of glyco-1-ynitols from these dibromocompounds. The 1,1-dibromo-1-alkenes were obtained by the reaction of dibromomethyl-triphenylphosphonium bromide in the presence of zinc in refluxing 1,4-dioxane. As an example, when the reaction is performed on 2-deoxy-5-O-trityl-d-ribofuranose (1) the corresponding 1,1-dibromo-1-olefin, (2R,3S)-6,6-dibromo-1-O-trityl-hex-5-ene-1,2,3-triol (12), is obtained in 89% yield. These smooth reaction conditions led also to the achievement of the other olefins from other sugars with good yields (44-90%). The reaction of these olefins with n-butyllithium in THF at low temperature afforded the corresponding alkynes. So the reaction of (2R,3S)-6,6-dibromo-1-O-trityl-hex-5-ene-1,2,3-triol (12) with this alkyllithium reagent led to (2R,3S)-1-O-trityl-hex-5-yne-1,2,3-triol (23) in 87% yield. Other glyco-1-ynitols were obtained with satisfying yields (64-87%).     

Cyclocondensations of (+)-camphor derived enaminones with hydrazine derivatives

Reactions of 3-[(E)-(dimethylamino)methylidene]-(+)-camphor and (1R,5S)-4-[(E)-(dimethylamino)methylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one with hydrazine derivatives were studied. Treatment of 3-[(E)-(dimethylamino)methylidene]-(+)-camphor with hydrazines afforded the corresponding fused pyrazoles. Similarly, fused pyrazoles were obtained upon reaction of (1R,5S)-4-[(E)-(dimethylamino)methylidene]-1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one with ortho-unsubstituted phenylhydrazines, while reactions with ortho-substituted phenylhydrazines and with hydrazine hydrochloride resulted in ‘ring switching’ type of transformation to furnish 2-aryl-4-[(1S,3R)-3-hydroxy-2,2,3-trimethylcyclopentyl]-1,2-dihydro-3H-pyrazol-3-ones.     

Studies on Reactions of Cyclic Oxalyl Compounds with Hydrazines or Hydrazones. 2. Synthesis and Reactions of 4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic Acid

4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid, obtained from the corresponding furan-2,3-dione and N-benzylidene-N'-(4-nitrophenyl)hydrazine, was converted via reactions of its acid chloride with various alcohols or N-nucleophiles into the corresponding ester or amide derivatives. The nitrile of the starting acid and 1-(4-aminophenyl)-4-benzoyl-5-phenyl-1H-pyrazole-3-carboxylic acid were also obtained. While cyclocondensation reactions of the two acids and the nitrile mentioned with hydrazines lead to pyrazolo[3,4-d]pyridazine derivatives, the reaction of starting acid with 2-hydrazinopyridine provided the hydrazonopyrazole acid derivative.     

Sequential synthesis of a new analogue of amlodipine bearing a short amino polyethyleneglycol chain

3-Ethyl 5-methyl 2-[(2-(2-(2-aminoethoxy)ethoxy)ethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate as new analogue of amlodipine was prepared in five steps with an overall yield of 22%. The 1,4-dihydropyridine nucleus was built in two steps via Knoevenagel reaction and the amino group of this analogue has been prepared in good yield by Staudinger reduction of the azido 1,4-dihydropyridine precursor in the last step.