Hydrazino Compound Research Articles

Novel Synthesis and Antimicrobial Activity of 3‐Substituted 5‐bromo‐7‐methyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles

4‐Methyl acetanilide (1) on treatment with bromine in acetic acid, followed by hydrolysis with dilute HCl/NaOH solution, yielded 2‐bromo‐4‐methyl aniline (2), which on treatment with sodium thiocyanate in acetic acid afforded 2‐amino‐4‐bromo‐6‐methyl benzothiazole (3). Compound 3 in ethylene glycol was heated at 150°C with 80% hydrazine hydrate to get 4‐bromo‐2‐hydrazino‐6‐methyl benzothiazole (4). This hydrazino compound 4 on heating with formic acid for 3 h yielded 4‐bromo‐2‐hydrazinoformyl‐6‐methyl benzothiazole (5). Same compound 4 when heated independently with formic acid for 6 h/urea for 3 h/carbon disulfide in alkali afforded 5‐bromo‐7‐methyl (6)/5‐bromo‐3‐hydroxy‐7‐methyl (7)/5‐bromo‐3‐mercapto‐7‐methyl (8)‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles, respectively. Compound 4 on heating with acetic acid/acetic anhydride gave acetyl benzothiazolyl derivative 9, which on cyclization with orthophosphoric acid yielded 5‐bromo‐3,7‐dimethyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazole (10). All these newly synthesized compounds were screened for antimicrobial activity against Escherichia coli (Gram −ve), Bacillus subtilis (Gram +ve), Erwinia carotovora, and Xanthomonas citri using ampicillin, streptomycin, and penicillin as a standard for comparison.

ChemInform Abstract: Synthesis of Some Thiazolo(5,4-d)pyrimidines.

Abstract 4-Amino-3-phenyl-2-thioxothiazol-5-carboxamide (1) reacts with aromatic aldehydes to form thiazolo-pyrimidines (2a,b ), and with acetic anhydride to thiazolopyrimidine (2C ). Thiazolocarboxamides (1a,b ) were converted to thiazolotriazines (3a,b ) by reaction with nitrous acid. When thiazolopyrimidine (2C ) was refluxed with POCl3, the corresponding chlorothiazolopyrimidine (4) was isolated. The produced chloro compound (4) can be converted into the corresponding thiazolopyrimidindithiones (5) or substituted aminothiazolopyrimidines (6,7), when allowed to react either with thiourea, aromatic amine or hydrazine hydrate. S-alkylated thiazolopyrimidines (8a-k ) were produced when compound (5) was reacted with halo compounds or acrylonitrile. Hydrazino compound (7) reacts with acetylacetone to produce the pyrazolylthiazolopyrimidine (9).

Promising antimicrobial agents: Synthetic approaches to novel tricyclic and tetracyclic pyrimidinones with antimicrobial properties

Abstract magnified image New tricyclic pyrimidinone derivatives were obtained from the corresponding thiazolopyrimidinone or hydrazino systems. The annelation of tricyclic hydrazino compound with 1,2,4‐triazole and tetrazole moieties gave novel tetracyclic condensed pyrimidinones. The investigation of the antimicrobial properties of tricyclic and tetracyclic pyrimidinones, by agar‐well diffusion assay, was carried out against six pathogenic bacteria (Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp, and Salmonella typhyrium) and four pathogenic fungi (Aspergillus flavus, Aspergillus niger, Aspergillus fumigatus, and Trichderma horozianum). Most of the compounds tested exhibited some degree of antimicrobial activity against microorganisms. Among these compounds, 4‐benzylidenhydrazino‐8‐cyano‐7‐(furan‐2‐yl)thiazolo[3,2‐a:4,5‐d′]dipyrimidin‐9‐one (12) showed the most favorable antibacterial activity, while compound 17 showed the highest effect on fungi. Interestingly, tetrazole derivative 19 displayed a remarkable effect on fungi much more than the corresponding 3‐substituted triazole derivatives on the one hand, whereas the lowest effect on bacteria on the other. J. Heterocyclic Chem., (2010).

Synthesis and Antimicrobial Activities of Some New Thieno and Furopyrimidine Derivatives

Fused pyrimidines, 8,9-dimethyl[1,2,4]triazolo[4,3-c]thieno[3,2-e]pyrimidine 5, 3,8,9-trimethyl[1,2,4]triazolo[4,3-c]thieno[3,2-e]pyrimidine 6, 4-benzylidinehydrazono-5,6 dimethylthieno[2,3-d]pyrimidine 7, 4-[4/-hydroxybenzylidine]hydrazono-5,6-dimethylthi-eno[2,3-d]pyrimidine 8, 4-[4/-tolylidin]hydrazono-5,6-dimethylthieno[2,3-d]pyrimidine 9, 4-[4/-nitrobenzylidine]hydrazono-5-ethyl-6-methylthieno[2,3-d]pyrimidine 10 and 4-[4/-chlorobenzylidine]hydrazono-5-ethyl-6-methylthieno[2,3-d]pyrimidine 11 are prepared in good yield by an initial treatment of 2-amino-4,5-dimethylthiophene-3-carbonitrile 1 with formic acid, affording 5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one 2, which is chlorinated with thionyl chloride and then hydrazinated with hydrazine hydrate. Finally hydrazino compound 4 is reacted with formic acid, acetic anhydrate, benzaldehyde, p-hydroxybenzaldehyde, p-toluayldehyde, p-nitrobenzaldehyde and p-chlorobenzaldehyde to give thienotriazolopyrimidines 5-6 and thienopyrimidines 7-11 respectively. All the compounds have been screened for their antimicrobial activity. Keywords: Fused pyrimidines; Hydrazino compound; Thienotriazolopyrmidines; Thienopyrimidines; Antimicrobial activity.© 2009 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.DOI: 10.3329/jsr.v1i2.2299

Synthesis of some new 4-styryltetrazolo[1,5- a]quinoxaline and 1-substituted-4-styryl[1,2,4]triazolo[4,3- a]quinoxaline derivatives as potent anticonvulsants

4-Methyltetrazolo[1,5- a]quinoxaline ( 3) was prepared by the azide cyclocondensation of 2-chloro-3-methylquinoxaline ( 2). The reaction of 3 with aromatic aldehydes furnished 4-styryltetrazolo[1,5- a]quinoxalines ( 4a– f). Compound 2, on treatment with hydrazine hydrate gave 2-hydrazino-3-methylquinoxaline ( 5). The ring closure of 5 was achieved by the reaction of orthoesters and trifluoroacetic acid to yield 4-methyl-1-(substituted)[1,2,4]triazolo[4,3- a]quinoxalines ( 7a– c). Further, reaction of 7a– c with different aromatic aldehydes furnished the title compounds, 4-styryl-1-(substituted)[1,2,4]triazolo[4,3- a]quinoxalines ( 8a– i) in good yield. In another scheme, the hydrazino compound 5 was treated with different aromatic aldehydes to yield corresponding N-arylidenehydrazino quinoxalines ( 6a– d). Further, the oxidative cyclization of hydrazones by nitrobenzene yielded 1-aryl-4-methyl[1,2,4]triazolo[4,3- a]quinoxalines ( 7d– g), which on condensation with aromatic aldehydes gave the title compounds, 1-aryl-4-styryl[1,2,4]triazolo[4,3- a]quinoxalines ( 8j– u). The newly synthesized compounds have been characterized by FTIR, 1H NMR, 13C NMR and mass spectral data, followed by elemental analysis. Some of the compounds were screened for in vivo anticonvulsant activity. Few of them exhibited promising results.

Synthesis of Certain Fused Thienopyrimidines of Biological Interest

4-(4-Acetylphenylamino)cycloocteno[4,5]thieno[2,3-d]pyrimidine (4) was prepared and condensed with certain aldehydes, phenylhydrazine, malononitrile to obtain 5a-d, 6 and 7, respectively. 4-Hydrazino & 4-substituted amino derivatives of 2-arylcycloocteno[4,5]thienopyrimidines 10a-c & 11a-i were synthesized. Cyclization of the hydrazino compounds 10a-c with orthoalkanoate esters or the arylidene derivatives 12a-c with bromine in acetic acid afforded the fused triazolo system 13a-i. Reaction of the hydrazino compound 10c with acetic anhydride gave 15 while the reaction of 10b,c with acid chlorides gave 16a-d. Furthermore, the tetrazolothienopyrimidines 17a-c were synthesized. Some of the newly synthesized compounds were tested for their antimicrobial activity.

Synthesis and Reactions of Novel Pyrimido[4,5‐c]pyridazine and s‐Triazolo[3′,4′:2,3]pyrimido[4,5‐c]pyridazine Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and Reactions of Novel Pyrimido[4,5-c]pyridazine and s-Triazolo[3?,4?:2,3]pyrimido[4,5-c]pyridazine Derivatives

The reaction of 3-chloro-5,6-diphenylpyridazine-4-carbonitrile with potassium thiocyanate gave the corresponding isothiocyanate derivative. This was reacted with aromatic amines in ethanol to afford pyrimido[4,5-c]pyridazine derivatives. The reaction of the latter compounds with hydrazine hydrate led to the formation of 6-hydrazino derivatives. One hydrazino compound was reacted with a variety of reagents to produce other new pyrimidopyridazines as well as a number of s-triazolo derivatives.

Synthetic Approach to 6-Benzoyl-2H-[1,2,4]triazine-3,5-dione and 6-Benzyl-5-thioxo-3,4-dihydro-2H-[1,2,4]triazin-3-one and Studies on Their Transformation to Fused[1,2,4]triazine Systems

Reaction of phenylpyruvic acid with semicarbazide afforded 6-benzyl-2H-[1,2,4]triazine-3,5-dione ( 1 ) which upon oxidation with potassium dichromate furnished 6-benzoyl-2H-[1,2,4]triazine-3,5-dione ( 2 ) in good yield. Constructing pyrazolo[3,4-e][1,2,4]triazine system ( 4 ) was achieved by reacting 2 with arylhydrazines in ethanolic solution. However treatment of 2 with the less reactive heteroarylhydrazines gave only the corresponding hydrazones ( 3 ). Attempt for constructing 1,2,4,5,10-pentaaza-dibenzo[a,d]cyclohept-3-one ( 7 ) from 2 was failed and (benzoimidazol-2-yl) [1,2,4] triazine derivative ( 6 ) was the only product. Reaction of 1 with phosphorus pentasulphide afforded compounds 8 and 9 . Compound 8 was transformed to the hydrazino compound 14 , which led to the construction of triazolo[4,3-d] [1,2,4]triazine system. Thus compounds 15 and 16 were obtained by reacting 14 with carbon disulfide or acetic anhydride respectively. Attempt to couple 8 with chloroacetic acid failed, while it's known isomer 10 led to the formation of thiazolo [2,3-c] [1,2,4]triazine derivative ( 13 ). Simple theoretical calculation using AM1 and PM3 semiempirical Hamitonian provided rational ways to correlate the reactivity with structure proposed.

Hypervalent Iodine Mediated Synthesis of 1,2,4‐Triazolo[4,3‐a][1,8]naphthyridines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Chiral Zirconium-Catalyzed Asymmetric Mannich-Type Reactions Using Acylhydrazones as Imine Equivalents

Abstract In the presence of a catalytic amount of a new zirconium catalyst, prepared from zirconium(IV) t-butoxide and (R)-3,3′-dibromo-1,1′-bi-2-naphthol, 4-trifluoromethylbenzoylhydrazones reacted with silyl enolates to afford the corresponding adducts, β-N′-acylhydrazinocarbonyl compounds, in good yields with high enantiomeric excesses. Reductive cleavage of the nitrogen-nitrogen bond of the hydrazino compound using samarium diiodide gave a chiral β-aminocarbonyl compound. In addition, the hydrazino compound was also successfully converted to chiral β-lactam and pyrazolidinone derivatives.

SYNTHESIS OF SOME THIAZOLO[5,4-D] PYRIMIDINES

Abstract 4-Amino-3-phenyl-2-thioxothiazol-5-carboxamide (1) reacts with aromatic aldehydes to form thiazolo-pyrimidines (2a,b ), and with acetic anhydride to thiazolopyrimidine (2C ). Thiazolocarboxamides (1a,b ) were converted to thiazolotriazines (3a,b ) by reaction with nitrous acid. When thiazolopyrimidine (2C ) was refluxed with POCl3, the corresponding chlorothiazolopyrimidine (4) was isolated. The produced chloro compound (4) can be converted into the corresponding thiazolopyrimidindithiones (5) or substituted aminothiazolopyrimidines (6,7), when allowed to react either with thiourea, aromatic amine or hydrazine hydrate. S-alkylated thiazolopyrimidines (8a-k ) were produced when compound (5) was reacted with halo compounds or acrylonitrile. Hydrazino compound (7) reacts with acetylacetone to produce the pyrazolylthiazolopyrimidine (9).

Heterocyclic studies. Part 44. Novel tricyclic compounds containing the pyrimido[5,4-d]-1,2,3-triazine system

Treatment of methyl 8-amino-5-chloro-2,3-dihydroimidazo[1,2,-c]pyrimidine-7-carboxylate with suitable amines and then nitrous acid gave derivatives (4) of the novel heterocyclic system imidazo[1′,2′:1,6]pyrimido[5,4-d][1,2,3]triazine. The same heterocyclic system in the form of an 8-oxide derivative (5) resulted from nitrous acid treatment of 8-amino-5-methylamino-7-methyl-2,3-dihydroimidazo[1,2-c]pyrimidine hydrochloride. In a similar way nitrous acid treatment of suitable imidazo- and pyrimido-[1,2-a]pyrimidine hydrochlorides (6; n= 1 or 2) yielded examples of the new heterocyclic systems imidazo- and pyrimido-[2′1′:2,3]pyrimido[5,4-d][1,2,3]triazine (7; n= 1 or 2).The synthesis of some triazolo-[4,3-a]- and -[1,5-a]-pyrimidines is described and one of these was converted into the 5-morpholino-8-oxide derivative of the novel [1,2,4]triazolo[3′,4′:2,3]pyrimido-[5,4-d][1,2,3]triazine system, compound (14). Acylation of 4-hydrazino-6,8-bisdimethylamino-pyrimido[5,4-d]-1,2,3-triazine (15; R1= R2= NMe2, R3= NHNH2) and cyclisation of the products gave derivatives of the new pyrimido[4,5-e]-1,2,4-triazolo[4,3-c][1,2,3]triazine system (16; R = H, Me, Et, CHCl2, or NH2). However, the benzoylhydrazino compound failed to cyclise in polyphosphoric acid and gave, instead, an oxadiazolyl pyrimidine (18; Scheme 2). The hydrazino compound (15; R1= R2= NMe2, R3= NHNH2) gave a pyrimidotetrazolotriazine (22) on treatment with nitrous acid, and a novel pyrimido[4,5-e][1,2,4]triazino[4,3-c][1,2,3]triazine (23) on treatment with pyruvic acid.

Linearly fused isoquinolines. Part II. The synthesis of the s‐triazolo[4,3‐b]isoquinoline system

Abstract3‐Hydrazinoisoquinoline (2) was synthesized via its N‐oxide derivative by removal of the N‐oxide funçtion with titanium trichloride. Acylation of the hydrazino compound (2) led to suitable starting materials (4 and 6) for cyclization to the novel, linearly fused ring system: tri‐azolo[4,3‐b]isoquinoline, which was more stable in the form of its perchlorate salt. The structure of the first representatives of the new ring system was proved by ir, nmr and ms spectroscopy.

Studies of Acenaphthene Derivatives. XVII. The Reaction of Benzylideneacenaphthenone with Hydrazines

Abstract The reactions of benzylideneacenaphthenones with hydrazines are reported. The reaction of benzylideneacenaphthenone with hydrazine hydrate in methanol at 40°C gave 1-hydroxy-2-hydrazinobenzylacenaphthylene, which was then cyclized to the 1-acetylpyrazoline by treating it with acetic anhydride. The hydrazino compound reacted with phenyl isocyanate to give the 1:2-adduct, which, when then treated with hydrochloric acid, suffered ring closure to the pyrazoline compound. Under severe conditions with hydrazine hydrate, however, the reductive cleavage reaction took place, giving the hydrazones of both acenaphthenone and benzaldehyde. Similar phenomena were also observed in the reaction with p-substituted benzylideneacenaphthenones. On the other hand, the reaction with phenylhydrazines in ethanol containing sulfuric acid afforded directly the expected pyrazolines, from which pyrazoles were then prepared by treating them with lead tetraacetate. Furthermore, the corresponding pyridazine was formed in the reaction of phenacylideneacenaphthenone with hydrazine hydrate, while the reaction with 2,4-dinitrophenyl-hydrazine gave the pyrazoline compound.

Effect of analogs of phenylalanine and tryptophan on kinetics of DOPA decar☐ylase in rat brain

A simple reaction vessel was designed to study the kinetics of DOPA decar☐ylase by trapping labeled CO 2 liberated from car☐yl- 14C- dl-DOPA. The effect of some analogs of phenylalanine and tryptophan on the rate of action of this enzyme was evaluated. The rate of decar☐ylation of l-DOPA by rat brain homogenates was 540 μg per g of tissue per h (V max) at pH 7.3 and 37°. The value of K m was1.5 × 10 −4 M. 5-HTP had a higher affinity for the enzyme than had l-DOPA, as determined by the percent inhibition of decar☐ylation of the latter produced by the addition of 5-HTP to the reaction mixture. α-Methyl DOPA was a competitive inhibitor, producing a 50% inhibition at10 −5 M. α-Hydrazino- α-methyl DOPA produced a 50% inhibition at1 × 10 −6 M with 10 μg/ml and a 75% inhibition with 1 μg/ml of pyridoxal-5-phosphate. The hydrazino compound exerted its effect by partly inactivating the coenzyme. Phenylalanine, tyrosine, o-fluorophenylalanine, m-fluorophenylalanine exerted weak inhibitory effects (10 to 20% at1 × 10 −3 M). Of 11 tryptophan analogs (including 5-HTP), the most active inhibitors were 6-amino- dl-tryptophan (20% at1 × 10 −4 M) and 5-benzyloxy- dl-tryptophan (15% at1 × 10 −4 M).

Potential anti-cancer agents. XII. Synthesis of 4-azido-3,6-dimethoxypyridazine derivatives.

4-Azido-3, 6-dimethoxypyridazine (X) was synthesized from 4-chloro-3, 6-dimethoxypyridazine (VII) through the hydrazino compound and X was converted to 4-azido-3, 6-dimethoxypyridazine 1-oxide (XII). Besides, some reactions of 4-chloro-3, 6-dimethoxypyridazine 1-oxide (I) and XII were examined.

ピラジン関連化合物の合成 (第4報)

2-Chloro-3-R-quinoxaline (R=OCH3, OC2H5, OCH(CH3)2, OC4H9, OCH2CH(CH3)2, OCH(CH3)(C2H5)) is prepared by addition of sodium alkoxide to 2, 3-dichloroquinoxaline. Addition of hydrazine hydrate to it easily gives 2-hydrazino-3-R-quinoxaline. This hydrazino compound undergoes cyclization to 1-substituted 4-R-s-triazolo[4, 3-a]quinoxaline by reaction with ortho-ester and acetic anhydride. Although it undergoes cyclization to the triazole compound by reaction with formic acid, R is hydrolyzed when it is OCH(CH3)2 and OCH(CH3)(C2H5), and forms s-triazolo[4, 3-a]quinoxalin-4-ol. Heating of 1-methyl-4-methoxy-s-triazolo[4, 3-a]quinoxaline to above its melting point results in rearrangement of the methyl group in methoxyl to the nitrogen in 5-position to form 1, 5-dimethyl-s-triazolo[4, 3-a]quinoxalin-4(5H)-one.

チオセミカルバチッド関連化合物の合成 (第1報)

1) Eighteen kinds of new 5-substituted (CH3, H) 2-benzylidenehydrazino-1, 3, 4-thiadiazoles were prepared by the condensation of 5-substituted 2-hydrazino-1, 3, 4-thiadiazole and aromatic aldehydes, and their antibacterial power were examined.2) 5-Substituted 2-hydrazino-1, 3 4-thiadiazoles were obtained either from 5-substituted 2-amino-1, 3, 4-thiadiazoles by diazotization through 5-chloro compound and application of hydrazine hydrate, or from 5-nitrosamino or 5-nitramino compound by reduction with zinc dust and acetic acid to the hydrazino compound.3) Ethyl thiosemicarbazonoformate was obtained by the reaction of thiosemicarbazide and ethyl orthoformate and this was led to 2-amino-1, 3, 4-thiadiazole and 3-mercapto-4, 1, 2-triazole.