Phosphonylation of a polypentenamer and preparation of its hydrogenated derivatives

Phosphonylated derivatives of a polypentenamer (PP) containing 82% trans and 17% cis double bonds have been prepared by the free-radical addition of dimethylphosphite to the double bonds and subsequent hydrogenation of the residual unsaturation. In this way derivatives were prepared containing approximately 5 and 10 mole % dimethylphosphonate side groups. These side groups were further reacted by hydrolysis or neutralization to form phosphonic acid and cesium phosphonate salts. Reaction conditions were so chosen that no backbone degradation occurred, and side reactions leading to crosslinking were avoided. The derivatives were characterized by gel-permeation chromatography (GPC), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy, and nuclear magnetic resonance spectroscopy. It was found that increasing substituent concentration decreases the melting point T_m in the case of the hydrogenated derivatives and increases the glass transition temperature T_g in the case of the unhydrogenated derivatives. The free acid derivatives are the least thermally stable of all those studied and the hydrogenated derivatives are generally more stable than the unhydrogenated derivatives.     

Cycloaddition Reactions of Benzonorbornadiene and Homonorbornadiene: New Isoxazoline and Pyridazine Derivatives

Ten new isoxazoline derivatives were synthesized from the reactions of benzonorbornadiene and homonorbornadiene derivatives with nitrile oxides formed from benzaldehyde and 4‐substituted benzaldehyde. Two new pyridazine derivatives were also synthesized from the reaction of the homonorbornadiene derivatives with 3,6‐di (2‐pyridyl)‐s‐tetrazine. It was seen that all cycloaddition reactions were realized as exo selectivity. Finally, γ‐Gauche effect in the isoxazoline derivatives was discussed.     

Synthesis of 1,2-Diazol-4-sulfonamides, 1,2,4- and 1,2,5-Oxadiazol-3-sulfonamides, 1,2,3-Triazol-4-sulfonamides, and Pyrimidine-5-sulfonamides starting from Cyanomethanesulfonyl Chloride

Summary. Cyanomethanesulfonyl chloride was reacted with amines yielding cyanomethanesulfonamides which could be transformed into alkoxymethylidene and aminomethylidene derivatives. The reaction of alkoxymethylidene derivatives with phenylhydrazine resulted in the formation of 5-aminopyrazol-4-sulfonamides, whereas from cyanomethanesulfonamides via the N-hydroxyamidine derivatives and their reaction with esters 1,2,4-oxadiazol-3-methanesulfonamides became accessible. Nitrosation of cyanomethanesulfonamides yielded 2-hydroxyimino derivatives which were then transformed into 2-hydroxyimino N-hydroxyamidine derivatives, and finally cyclized into 4-amino-1,2,5-oxadiazol-3-sulfonamides. On the other hand diazotation of cyanomethanesulfonamides gave the 2-arylhydrazono derivatives, which after transformation into N-hydroxyamidine derivatives gave by reaction with POCl₃ 5-amino-1,2,3-triazol-4-sulfonamides. Finally, the reaction between cyanomethanesulfonamides and formamidinium acetate opened an easy access to 4-aminopyrimidine-5-sulfonamides, which could be transformed by trialkyl orthoformiates into substituted pyrimidino[4,5-e][1,2,4]thiadiazine derivatives. All intermediates as well as transformation products of the heterocyclic systems were isolated and well characterized. Mechanisms were discussed, and the stereochemistry, when necessary and possible, was elucidated.     

Synthesis and antimicrobial evaluation of new 2-pyridinone and 2-iminochromene derivatives containing morpholine moiety

As trail to overcome on the antimicrobial drug-resistance problems, new functionalized 2-pyridinone and 2-iminochromene derivatives bearing morpholine moiety were designed and synthesized. The 2-pyridinone derivatives were obtained through the cyclization of cyanoacetohydrazone of 4-morpholinylacetophenone with 1,3-dicarbonyl compounds, α,β-unsaturated nitriles or 2-(arylidene)malononitriles. The 2-iminochromene derivatives were synthesized through the ring closure of cyanoacetohydrazonewith salicylaldehyde derivatives. The antibacterial and antifungal activities for the synthesized 2-pyridinone and 2-iminochromene derivatives were investigated. Most of the tested compounds showed moderate activity against P. vulgaris. Compounds 4a,b and 5a,b showed moderate activity against G −ve bacteria. All iminochromene derivatives showed moderate activity against C. albicans. Compound 8c was the most active compound.     

On triazoles. XXIX. The reaction of triazolyl thiohydrazides with isocyanates and isothiocyanates

Different N-methylsubstituted, N'-methylsubstituted and N,N'-unsubstituted triazol-1-ylcarbothiohydrazides were reacted with isocyanates and isothiocyanates to yield the corresponding carbamoyl and thiocarbamoyl derivatives 4 . The thiocarbamoyl derivatives could be cyclised by heating in dimethylformamide or 10% sodium hydroxide solution, reacting them with dicyclohexylcarbodiimide or thier alkylation to the corresponding 1,3,4-thiadiazoles 12 and 16 , and derivatives 5 formed by splitting the triazole moiety. Cleaved derivatives 9 and 11 were also formed in the reaction of thiocarbamoyl derivatives 4 with carbon disulfide in the absence or presence of methyl iodide, respectively. Spectroscopic evidence is given for the structure of products obtained.     

Geminal systems. 50. Synthesis and alcoholysis of N-acyloxy-N-alkoxy derivatives of ureas,carbamates, and benzamides

Procedures were developed for the synthesis of N-acyloxy-N-alkoxy derivatives of ureas, carbamates, and benzamides by the reactions of the corresponding N-alkoxy-N-chloro derivatives with sodium carboxylates in MeCN. N-Chloro-N-ethoxy-p-toluenesulfonamide was inert in this reaction. Alcoholysis of N-acyloxy-N-alkoxy derivatives of ureas, carbamates, and tert-alkylamines afforded the corresponding N,N-dialkoxy derivatives, whereas alcoholysis of N-acetoxy-N-ethoxybenzamide gave rise to alkyl benzoates.     

Synthesis and biological activity of new 1,3,4-thiadiazole derivatives

The aminothiadiazole (II) on treatment with aromatic aldehydes yielded Schiff bases, which cyclized to thiazolidinone derivatives by reaction with thioglycolic acid. Reaction of II with phenyl isocyanate and phenyl isothiocyanate afforded the carbamide and carbothiamide derivatives, respectively, which on reaction with malonic acid in acetyl chloride gave barbituric and thiobarbituric acid derivatives. However, reaction of carbon disulfide and methyl iodide with II gave dithiocarbamidate derivative which on treatment with ethylenediamine or o-phenylenediamine gave the condensed N-imidazolylthiadiazolylamine derivatives.     

Microwave assisted synthesis and antimicrobial evaluation of novel substituted thiosemicarbazide derivatives of pyrimidine

A new series of antimicrobial thiosemicarbazide substituted pyrimidine derivatives were synthesized by using thiosemicarbazide and ethyl 2-((2-amino-5-carbamoyl-6-[substituted benzyl] pyrimidin-4-yl)oxy)acetate derivatives and subsequent addition of acetaldehyde and acetone. The designed compounds were screened for Antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia in comparison with the standard drugs Ciprofloxacin and antifungal effect against Aspergillus niger and Aspergillus fumigates in comparison with the standard drug Ketoconazole reveal the potency of synthesized derivatives. In accordance with the data obtained from antimicrobial activity, all the synthesized derivatives have shown good activity against the tested microbes. Among them, compound bearing 2-hydroxy and 3-chloro derivatives of thiosemicarbazide substituted pyrimidine has shown good activity against all the tested organisms.     

Synthesis of New Pyrrolo Heterocycles (I): Novel Synthesis of Pyrano[2,3‐c]pyrrole,Isoindoline, Pyrrolo[3,4‐b]pyridine,and Pyrrolo[3,4‐d]pyrimidine Derivatives

Michael addition of 1,5‐diaryl‐2,3‐dioxopyrrolidine derivatives with α‐cyanocinnamonitriles and ethyl α‐cyanocinnamates afforded 4H‐pyrano[2,3‐c]pyrrole derivatives in the presence of sodium ethoxide. Under the same reaction condition, the ylidenes of 1,5‐diaryl‐2,3‐dioxopyrrolidine were reacted with malononitrile or ethyl cyanoacetate to give isoindole derivatives; however, pyrrolo[3,4‐b]pyridine derivatives were formed when cyanoacetamide was used. Moreover, pyrrolo[3,4‐d]pyrimidine derivatives were synthesized by treating 4‐benzylidene‐1,5‐diphenyl‐2,3‐dioxopyrrolidine with urea and/or thiourea under basic conditions. The structures of all the new synthesized compounds were confirmed by elemental analysis, IR and NMR spectra.     

QSPR study on pK<Subscript>a</Subscript> values of N-methoxy-polynitroaniline derivatives

A QSPR study is presented for acidities of thirteen N-methoxy-polynitroaniline derivatives. Hammett σ values are known for meta and para substituents, and in the present study values are introduced for ortho-substituents in these N-methoxy-polynitroaniline derivatives. Hammett σ values for ortho-substituents in these N-methoxy-polynitroaniline derivatives were obtained by multiplying para values with 0.65.     

Synthesis of New Chromeno[4,3‐b]pyrazolo[4,3‐e]pyridines Derivatives with Antimicrobial Evaluation

A series of 2‐oxo‐2,5‐dihydro‐1H‐chromeno[4,3‐b]pyridine derivatives were obtained by using a one‐pot three component reaction of 2,2‐disubstituted chroman‐4‐one with aromatic aldehydes and 2‐cyanoacetamide in the presence of sodium hydroxide under solvent‐free conditions. Heating chromenopyridine derivatives with phosphoryl chloride gave the corresponding chloro derivatives. The reaction of the chloro derivatives with hydrazine hydrate afforded dihydrochromeno[4,3‐b]pyrazolo[4,3‐e]pyridines derivatives. Condensation of the dimethyl derivative compound with the aromatic aldehydes gave 8‐Arylideneamino‐6,6‐dimethyl‐10H‐chromeno[4,3‐b]pyrazolo[4,3‐e]pyridine.     

Reactions with 2-mercaptopyrimidines. Synthesis of some new thiazolo[3,2-a]- and triazolo[4,3-a]pyrimidines

Alkylation of 5-cyano-4-oxo-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine I with methyl iodide, chloroacetic acid or 3-chloro-2,4-pentanedione, afforded the S-alkyl derivatives IIa-c. 2-Carboxymethylthio and 2-(2′,4′-dioxopentan-3-ylthio) derivatives IIb and IIc could be cyclised by acetic anhydride or polyphosphoric acid to give 6-cyano-3,5-dioxo-5H-7-phenylthiazolo[3,2-a]pyrimidine III and 2-acetyl-6-carboxamido-5H-3-methyl-7-phenylthiazolo[3,2-a]pyrimidine-5-one IX , respectively. Benzoylation of 2-hydrazinopyrimidine derivative XII , in anhydrous dioxan, afforded the N-benzoyl derivative XIII , which could be cyclised by heating in dimethylformamide to give 5-amino-6-cyano-3,7-diphenyl-s-triazolo[4,3-a]pyrimidine ( XIV ). The 2-hydrazinopyrimidine derivatives XII and XV reacted with benzoyl isothiocyanate in dioxane to yield 4-benzoylthiosemicarbazide derivatives XVI and XVII , which were converted into the 2-s-trizolopyrimidine derivatives XVIII and XIX , respectively. Also, XVI and XVII reacted with 2,4-pentanedione and 3-chloro-2,4-pentanedione to yield 2-pyrazolopyrimidine derivatives XX and XXI , respectively.     

Novel Synthesis and Structure of Phosphanyl Sugar Derivatives 1

Abstract

Some phosphanyl sugar derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen, were synthesized from 2- and 3-phospholenes as starting materials. Catalytic cis-dihydroxylation of 2-phospholene or 3-phospholene 1-oxide derivatives with osmium(VIII) oxide in the presence of a cooxidant afforded 3-deoxy- or 1-deoxy-tetrofuranose-type phosphanyl sugar derivatives, respectively. cis- Dihydroxylation of 4-acyloxy-2-phospholene 1-oxide derivatives gave tetrofuranose type phosphanyl sugar derivatives. Some of these derivatives of phosphanyl sugars were subjected to structural analyses using ¹H NMR and X-ray crystallography.

     

Synthesis and thermal properties of azo-peroxyesters

Abstract  

New azo-perester derivatives of tert-butyl and tert-amyl hydroperoxides were obtained in reactions of azo acid chlorides with hydroperoxides in the presence of an inorganic base. Obtained azo-peresters possess two kinds of the labile functional groups: the azo group and also the perester group. The data from DSC experiments indicate that in the case of azo-perester derivatives of tert-amyl hydroperoxide, the perester group decomposes at a somewhat lower temperature than in the case of tert-butyl derivatives, whereas azo groups decompose at somewhat higher temperature in the case of derivatives with tert-amyl substituent.     

Synthesis of 6-Heterocyclically Appended Tri-<Emphasis Type="Italic">O</Emphasis>-methyl Protected 6-Desmethyl Emodin Derivatives

Summary. A convenient synthesis of several 6-heterocyclically appended tri-O-methyl 6-desmethyl emodin derivatives including the tetrazolyl, oxazolyl, oxazolinyl, benzimidazolyl, benzoxazolyl, and benzothiazolyl derivatives of potential biological and medicinal interest was achieved starting from the tri-O-methyl protected emodin aldehyde or nitrile. In addition, these derivatives could serve as synthons for heterocyclic hypericin derivatives.     

Synthesis of novel bis(chromenes) and bis(chromeno[3,4-C]pyridine) incorporating piperazine moiety

Novel bis(2-oxo-2H-chromene) as well as bis(2-imino-2H-chromene) derivatives incorporating piperazine moiety were prepared by the cyclocondensation reaction of bis(2-hydroxybenzaldehyde) with two equivalents of each of the appropriate β-ketoesters or acetonitrile derivatives. The bis(2-imino-2H-chromene-3-carbothioamide) derivative was used as a key synthon for construction of novel bis(3-(4-substituted thiazol-2-yl)-2H-chromen-2-one) derivatives via its cyclocondensation with a series of the appropriate α-halocarbonyl derivatives. Moreover, the bis(2-hydroxybenzaldehyde) reacted with four equivalents of the appropriate acetonitrile derivatives to afford the corresponding bis(3H-chromeno[3,4-c]pyridine) derivatives. Elucidation of the structure of the novel bis(chromenes) bearing piperazine nucleus was established by the spectral data and elemental analyses.     

Reactions of some 4-methylene-4H-pyran derivatives with primary and secondary amines

4-Dicyanomethylene-4H-pyrans react with secondary amines to give 2-aminopyridine and 2-pyridone derivatives which, in turn, have been used to prepare copyrine derivatives. These pyrans and primary amines gave copyrine and iminopyridone derivatives in addition to the dicyanomethylene-1,4-dihydropyridines, which had been reported previously. Reaction of cyanocarbamoylmethylene-4H-pyrans with secondary amines gave 2-pyrones, and with primary amines, gave copyrines and 1,4-dihydropyridine derivatives.     

Synthesis of 6-Heterocyclically Appended Tri- O-methyl Protected 6-Desmethyl Emodin Derivatives

A convenient synthesis of several 6-heterocyclically appended tri-O-methyl 6-desmethyl emodin derivatives including the tetrazolyl, oxazolyl, oxazolinyl, benzimidazolyl, benzoxazolyl, and benzothiazolyl derivatives of potential biological and medicinal interest was achieved starting from the tri-O-methyl protected emodin aldehyde or nitrile. In addition, these derivatives could serve as synthons for heterocyclic hypericin derivatives.     

Synthesis of certain alkenyl purines and purine analogs

Synthesis of alkenyl derivatives of certain purines and purine analogs is described. Direct alkylation of the sodium salt of 6-chloropurine (1) either with 1-bromo-2-pentene or 4-bromo-2-methyl-2-butene in N,N-dimethylformamide furnished N-7, 4a and N-9, 3a , 3b alkenyl derivatives. Similar alkylation of 2-amino-6-chloropurine (2) provided the corresponding N-7, 4c-4e and N-9, 3c-3e alkenyl derivatives. Acid hydrolysis of these chloro derivatives 3a-3e, 4a,c-e furnished the corresponding alkenyl hypoxan-thines 6a, 6b and 7a or alkenyl guanines 6c-6e and 7c-7e. Treatment of 3a-3d with thiourea in absolute ethanol provided the corresponding 6-thio derivatives 5a-5d. Alkylation of the sodium salt of either purine-6-carboxamide (8) or 1,2,4-triazole-3-carboxamide (10) gave mainly one isomer 9a, 9b and 11a, 11b. The direct alkylation of pyrrolo[2,3-d]pyrimidin-4(3H)-one (12) gave N-3 alkenyl derivatives 13a, 13b , and the N-7 alkenyl derivatives 16a, 16b have been prepared starting from the 4-chloro derivative 14 . Synthesis of 2-amino-7-(2-penten-1-yl)pyrrolo[2,3-d]pyrimidin-4(3H)-one (19a) has been accomplished starting from 2-amino-4-methoxypyrrolo[2,3-d]pyrimidine (17) . These alkenyl derivatives were found to be devoid of anti-HCMV activity in vitro.     

3‐(3,5‐Dimethyl‐1H‐Pyrazol‐1‐yl)‐3‐Oxopropanenitrile as Precursor for Some New Mono‐Heterocyclic and Bis‐Heterocyclic Compounds

3‐(3,5‐Dimethyl‐1 H ‐pyrazol‐1‐yl)‐3‐oxopropanenitrile 1 was used as a cyanoacetylating agent for synthesis of the acetanilide derivative 3 . Compound 3 was utilized as a key intermediate for the synthesis of some new mono‐chromene and di‐chromene derivatives 9 and 13 , the dihydrazo derivatives 15 , and the dithiazole derivatives 18 via the condensation with o‐hydroxybenzaldehyde derivatives, the coupling with aryl diazonium salts, or the reaction with phenyl isothiocyanate in presence of KOH followed by phenacyl bromide derivatives respectively.