6,11-Dihydrodibenzo[b,e]thiepin-11-thiol and 11-acetic acid derivatives; Some 2-methyl-6,11-dihydrodibenzo[b,e]thiepins; Synthesis and pharmacological screening

1979 ◽  
Vol 44 (9) ◽  
pp. 2689-2701 ◽  
Author(s):  
Vladimír Valenta ◽  
František Kvis ◽  
Jiří Němec ◽  
Miroslav Protiva
Keyword(s):  
Acetic Acid ◽  
Zinc Chloride ◽  
Local Anaesthetic ◽  
Diethyl Malonate ◽  
Acetyl Derivative ◽  
Cardiovascular Activity ◽  
Starting Compound ◽  
Pharmacological Screening ◽  
Neurotropic Effects ◽  
Sodium Amide

11-Chloro-6,11-dihydrodibenzo[b,e]thiepin was transformed via the isothiourea V to the thiol IV which was used for the synthesis of aminoalkyl sulfides VII and VIII and of the methylpiperazide X. The same starting compound was used for alkylating diethyl malonate and via the intermediates XIV and XV, 6,11-dihydrodibenzo[b,e]thiepin-11-acetic acid (XVI) was obtained, which was converted to the methylpiperazide XVIII. Oxime XIX and 2-diethylaminoethylimine XX were prepared from 2-methyldibenzo[b,e]thiepin-11(6H)-one (II). Reduction of the ketone II afforded 2-methyl-6,11-dihydrodibenzo[b,e]thiepin (XII) giving by treatment with sodium amide and 3-dimethylaminopropyl chloride the amine XXIII. In the reaction of 6,11-dihydrodibenzo[b,e]thiepin-11-ol with sodium amide and 3-dimethylaminopropyl chloride, C-alkylation took place in addition to the expected etherification resulting in the diamine XXII. Reaction of phthalide with 4-aminothiophenol gave the acid XXIV which was transformed to the 3-dimethylaminopropyl ester XXV and N-acetyl derivative XXVI. Compound XXVI was cyclized with zinc chloride to the ketone III. Some of the compounds prepared exhibit structurally less specific peripheral and vegetative neurotropic effects (local anaesthetic, spasmolytic) and cardiovascular activity (antiarrhytmic).

1-(4-Cyclopentylphenyl)ethylamine and derivatives: Synthesis and pharmacological screening

1981 ◽  
Vol 46 (9) ◽  
pp. 2234-2244 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Jiří Holubek ◽  
Marie Bartošová ◽  
Miroslav Protiva
Keyword(s):  
Local Anaesthetic ◽  
Title Compound ◽  
Starting Material ◽  
Ritter Reaction ◽  
Hypotensive Activity ◽  
Substitution Reactions ◽  
Spasmolytic Activity ◽  
Pharmacological Screening ◽  
Neurotropic Effects ◽  
Derivatives Of

Reduction of 4-cyclopentylacetophenone oxime gave the title compound II which was transformed by a combination of acylation, alkylation, reduction and substitution reactions to compounds III-XI. 2-Benzylcyclopentanone oxime was reduced to 2-benzylcyclopentylamine (XVI) and converted by a reaction with methylmagnesium iodide and by the following Ritter reaction to the formamide derivative XVIII which was used as the starting material for preparing amines XIX-XXI. The local anaesthetic and spasmolytic activity were the most typical neurotropic effects of derivatives of compound II. 2-Benzyl-1-methylcyclopentylamine and derivatives XIX-XXI have some hypotensive activity.

Cyclic amidines derived from benz[c,d]indole and 4,5-dihydro-3H-1-benzazepine including some related compounds: Synthesis and pharmacological screening

1985 ◽  
Vol 50 (8) ◽  
pp. 1888-1898 ◽  
Author(s):  
Miroslav Protiva ◽  
Zdeněk Šedivý ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Jiří Němec
Keyword(s):  
Titanium Tetrachloride ◽  
Aqueous Sodium Hydroxide ◽  
Secondary Amines ◽  
Primary Amines ◽  
Open Chain ◽  
Lithium Aluminium ◽  
Pharmacological Screening ◽  
Antiinflammatory Effects ◽  
Related Compounds ◽  
Sodium Amide

Reactions of naphthostyril (I) with primary and secondary amines and titanium tetrachloride afforded cyclic amidines III-IX. Hydrogenation of I on Pd-C resulted in the 6,7,8,8a-tetrahydro derivative X which gave by treatment with sodium amide and 3-dimethylaminopropyl chloride the N-(aminoalkyl) compound XI. Reduction of I and its N-methyl derivative II with sodium amalgam in aqueous sodium hydroxide gave the 2a,3,4,5-tetrahydro derivatives XII and XIII. Reaction of XIII with sodium amide and 3-dimethylaminopropyl chloride afforded the 2a-(aminoalkyl) compound XIV. 1,3,4,5-Tetrahydro-1-benzazepin-2-one (XV) treated with primary amines and titanium tetrachloride gave the amidines XVI-XVIII. 3-Methyl-7,8,9,9a-tetrahydro-1H-benz[d,e]isoquinoline (XIX) was reduced with sodium borohydride to compound XX which was alkylated with propargyl bromide to 1-methyl-2-propargyl-2,3,3a,4,5,6-hexahydro-1H-benz[d,e]isoquinoline (XXI). An attempt to prepare the 2-(2-phenylethyl) analogue by treatment of compound XX with phenylacetyl chloride and by the following reduction with lithium aluminium hydride resulted in the open-chain amine XXII. The lactams I, II, X, and XIII showed some discoordinating, hypothermic, peripheral vasodilating, hyperglycaemic, diuretic and antiinflammatory effects. The amidines III-IX and XVI-XVIII had local anaesthetic, slight hypotensive, antiarrhythmic, peripheral myorelaxant, papaverine-like spasmolytic and thiopental potentiating effects.

Heterocyclic synthesis from 3-amino-4-cyanopyrazole

1990 ◽  
Vol 55 (3) ◽  
pp. 728-733 ◽  
Author(s):  
Ali Deeb ◽  
Medhat El-Mobayed ◽  
Abdel Naby Essawy ◽  
Adel Abd El-Hamid ◽  
Atef Mohamid Abd El-Hamid
Keyword(s):  
Acetic Acid ◽  
Zinc Chloride ◽  
Quinoline Derivative ◽  
Phenyl Isothiocyanate ◽  
Heterocyclic Synthesis

3-Amino-4-cyanopyrazole I reacts with hydroxylamine and with hydrazine to yield 1H,6H-3-aminopyrazolo[3,4-c]pyrazole (III and IV). Diazotized IV couples with 2-naphthol to give the arylazo derivative VI which cyclizes to 9H-naphthol[2,1-e]pyrazolo[3',4':3,4]pyrazolo[5,1-c]-[1,2,4]triazine VII by means of acetic acid. The pyrazol-5-ylthiourea obtained from I and phenyl isothiocyanate undergoes base-catalyzed cyclization to give pyrazolo[3,4-d]pyrimidinethione derivative IX. Compound I reacts with cyclohexane in the presence of zinc chloride to give the tetrahydropyrazolo[3,4-b]quinoline derivative XI. The reaction of I with pyridine 1-oxide affords 4H,5H-pyrazolo[5',1':2,3] [1,2,4]triazolo[1,5-a]pyridine-3-carbonitrile XII.

Novel Synthesis of 3-Spiroheterocycles-2-methylquinolin-4-one

1993 ◽  
Vol 58 (9) ◽  
pp. 2215-2221 ◽  
Author(s):  
Abd El-Hamid N. Ahmed
Keyword(s):  
Phthalic Anhydride ◽  
Zinc Chloride ◽  
Ethyl Acetoacetate ◽  
Diethyl Malonate ◽  
Novel Synthesis ◽  
Structure Similarity ◽  
New Compounds

2-Methyl[3,1]benzoxazin-4-one (I) is easily accessible , but its chemistry has not been investigated enough. Structure similarity between I and phthalic anhydride encouraged us to investigate the reaction of I with compounds bearing active methylenes namely diethyl malonate, ethyl acetoacetate and acetylacetone in presence of zinc chloride, Thus new compounds II, III and IV were synthesized. Those compounds were used as precursors for the synthesis of various spiroheterocycles.

scholarly journals Synthesis and evaluation of possible mechanism of anti nociceptive potential of novel 2-quinolone fused 3,5-pyrazolidinedione derivatives in experimental animal models

2013 ◽  
Vol 24 (1) ◽  
pp. 5-12
Author(s):  
Abhishek Tiwari ◽  
Anita Singh
Keyword(s):  
Acetic Acid ◽  
Analgesic Activity ◽  
Diclofenac Sodium ◽  
Diethyl Malonate ◽  
Plate Model ◽  
Model Compounds ◽  
Hot Plate ◽  
Standard Drug ◽  
Experimental Animal Models ◽  
Drug Compound

AbstractIn the present synthesis a series of 1-(1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-2-substituted phenylpyrazolidine-3,5-diones were prepared. By the reaction of N-methylbenzenamine with diethyl malonoate 4-hydroxy-1-methylquinolin-2(1H)-one were prepared, which on treatment with posphoryl chloride converted into 4-chloro-1-methylquinolin-2(1H)-one. Subsequently with substituted phenyl hydrazines 1-methyl-4-(2- substitutedphenylhydrazinyl)quinolin-2(1H)-one were obtained, which on reaction with diethyl malonate gave 1- (1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-2-substituted phenylpyrazolidine-3,5-diones. All structures were characterized by IR, 1HNMR & mass spectrometry. Further all the synthesized compounds were evaluated for their anti-nociceptive activity in mice by Eddy’s hot plate and acetic acid induced writhing response. All compounds have shown the activity. In hot plate model compounds QAA-04c and QAA-04d have given more activity than standard, whereas in case of acetic acid induced writhing model compounds QAA-04a and QAA- 04d have given significant analgesic activity which is comparable with the standard drug. Compound QAA-04b has shown least analgesic activity. Compound QAA-04a was almost equal in activity to the standard drug diclofenac sodium and was considered as the lead molecule.

scholarly journals INFLUENCE OF ADDITIVES OF ACID ON STAGE OF TRANSFORMATIONS OF 4-NITRO-2'-HYDROXY-5'-METHYLASOBENZENE ON SKELETONIC NICKEL IN WATER SOLUTION OF 2-PROPANOL

2020 ◽  
Vol 63 (7) ◽  
pp. 41-47
Author(s):  
Hoang Anh ◽  
Olga V. Lefedova ◽  
Alexandra.V. Belova
Keyword(s):  
Aqueous Solution ◽  
Acetic Acid ◽  
Maximum Yield ◽  
Bulk Solution ◽  
Skeletal Nickel ◽  
Acid Addition ◽  
Starting Compound ◽  
Conversion Rates ◽  
Azo Group ◽  
Neutral Aqueous Solution

The article is devoted to the analysis of the reaction kinetics of hydrogenation of 4-nitro-2'-hydroxy-5'-methylazobenzene in an aqueous solution of 2-propanol with acetic acid addition on skeletal nickel at different initial quantity of the starting compound. Clarification of the sequence of transformations of compounds containing several reactive groups, and the development of approaches to controlling the selectivity of processes with their participation is a practically significant task. According to the data obtained, at both low and high initial concentrations the hydrogenation of 4-nitro-2'-hydroxy-5'-methylazobenzene on skeletal nickel in a 2-propanol aqueous solution-0.01 M CH3COOH solvent proceeds in two parallel directions. The largest contribution in the first phase of the reaction is made by the azo group conversion of the starting compound, in contrast to the reaction in an aqueous solution of 2-propanol without acid addition. An increase in the initial quantity of the hydrogenated compound above its solubility limit leads to an increase in the rate of conversion of the azo group in 4-nitro- and 2-amino-2'-hydroxy-5'-methylazobenzene. Consequently, optimum quantity of 4-nitroaniline and 2-amino-2'-hydroxy-5'-methylazobenzene in the bulk solution during hydrogenation of the specified quantity of 4-nitro-2'-hydroxy-5'-methylazobenzene practically didn’t change, in contradiction to the hydrogenation on skeletal nickel in a neutral aqueous solution of 2-propanol. In a neutral aqueous solution of 2-propanol, when passing to high concentrations of the hydrogenated compound, the maximum yield of 4-nitroaniline increases twice as long the better, while as 4-amino-2'-hydroxy-5'-methylazobenzene, is reduced conversely. The results obtained do not contradict the concept of a parallel-sequential scheme for the conversion of 4-nitro-2'-hydroxy-5'-methylazobenzene. One of the directions involves the conversion of 4-nitro-2'-hydroxy-5'-methylazobenzene through 4-nitroaniline and 2-amino-4-methylphenol due to the hydrogenation of the azo group, and the second is the conversion of 4-nitro-2'-hydroxy-5'- methylazobenzene via 4-amino-2'-hydroxy-5'-methylazobenzene by reduction of the nitro group. At the end of the reaction, all the intermediate compounds are reduced to 2-amino-4-methylphenol and 1,4-phenylenediamine. When acetic acid is introduced into the composition of the neutral solvent 2-propanol-water, the contribution of the direction that ensures the formation of 4-nitroaniline and 2-amino-4-methylphenol to the overall reaction rate increases. An increase in the initial amount of 4-nitro-2′-hydroxy-5′-methyl-azobenzene leads to an increase in the rate of conversion of the azo group in the starting compound and to a decrease in the rate of conversion of 4-amino-2′-hydroxy-5′-methylazobenzene. The effect of the acid on the change in the conversion rates of nitro and azo groups to 4-nitro-2′-hydroxy-5′-methylazobenzene does not contradict the previously obtained results for the hydrogenation of its analogue, 2-nitro-2′-hydroxy-5-methylazobenzene, as well as individual compounds containing a nitro and azo group.

Fluorine-Containing Heterocycles: Part I. Synthesis of New 7-(2-thienyl)-9-Trifluoromethylpyrido[3′,2′:4,5]Thieno[3,2-d]Pyrimidines and Related Fused Tetracyclic Systems

2005 ◽  
Vol 2005 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Etify A. Bakhite ◽  
Abdu E. Abdel-Rahman ◽  
Elham A. Al-Taifi
Keyword(s):  
Acetic Acid ◽  
Acetic Anhydride ◽  
Formic Acid ◽  
Hydrazine Hydrate ◽  
Methyl Iodide ◽  
Phosphorus Oxychloride ◽  
Diethyl Malonate ◽  
Triethyl Orthoformate ◽  
Dimroth Rearrangement ◽  
Ethyl Chloroacetate

3-amino-6-(2-thienyl)-4-trifluoromethylthieno[2,3-b]pyridine-2-carboxamide (3) and 2-carbonitrile analogue 5 were prepared by reaction of 3-cyano-6-(2-thienyl)-4-trifluoromethylpyridine-2(1H)-thione (1) with chloroacetamide or chloroacetonitrile respectively. Heating compound 3 with triethyl orthoformate led to the formation of pyridothienopyrimidinone derivative 6. Reaction of 6 with phosphorus oxychloride produced 4-chloropyrimidine derivative 7 which underwent some nucleophilic displacements upon treatment with thiourea, piperidine, morpholine or hydrazine hydrate to give the target 4-substituted pyridothienopyrimidines 8, 10a, 10b and 11 respectively. Reaction of compound 8 with methyl iodide or ethyl chloroacetate gave compounds 9a,b. The condensation of 3-amino-6-(2-thienyl)-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carbonitrile (5) with triethyl orthoformate led to the formation of methanimidate derivative 21 which upon treatment with hydrazine hydrate gave the target 3-amino-3,4-dihydro-4-imino-7-(2-thienyl)-9-trifluoromethylpyrido[3′,2′:4,5] thieno[3,2-d]pyrimidine (22). The reactions of compounds 11 and 22 with some reagents namely; triethyl orthoformate, acetic anhydride, formic acid, acetic acid, acetylacetone benzaldehyde and/or diethyl malonate were carried out and their products were identified, in most cases as [1,2,4]triazolopyridothienopyrimidines via Dimroth rearrangement.

scholarly journals An Unusual Course of a Nitro Sugar Acetylation: Formation of a Crystalline Nitronic Acid – Acetic Acid Mixed Anhydride

1971 ◽  
Vol 49 (19) ◽  
pp. 3236-3238 ◽  
Author(s):  
Werner Rank ◽  
Hans H. Baer
Keyword(s):  
Acetic Acid ◽  
Acetyl Chloride ◽  
Acetyl Derivative ◽  
Acid Anhydride ◽  
Mixed Anhydride ◽  
Nitronic Acid

Whereas acetylation of methyl 4,6-O-benzylidene-3-deoxy-3-nitro-β-D-mannopyranoside (1) and its β-D-galacto isomer 2 with acetyl chloride and triethylamine in ether furnished the expected 2-O-acetylated nitro glycosides, 1a and 2a, the same method applied to the α-D-talo isomer 3 gave the 2-O-acetyl derivative of the corresponding nitronic acid – acetic acid anhydride, 4.

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