Synthesis of new arylidene derivatives of 3-aminorhodanine

The synthesis of new arylidene derivatives of 3 -aminorhodanine has been effected. It has been established that the condensation of 3-aminorhodanine with aldehydes in an alcoholic medium gives 3-arylidene derivatives. Similar reactions in an ammoniacal medium lead to 5-derivatives of 3-aminorhodanine. 3, 5-Diarylidene derivatives can be obtained by condensing 3-aminorhodanine with an excess of an aldehyde in glacial acetic acid, except for the salicylidene and 9-anthrylidene derivatives, the synthesis of which can be carried out only in two stages.     

The dual reactivity of 3-aminorhodanine

3-Aminorhodanine in ethanol reacts in the hydrazine form with aromatic aldehydes to give 3′-arylidene derivatives, while in ammonia it reacts in the tautomeric thiol form to give 5-arylidene derivatives. 3′, 5-Diarylidene derivatives of 3-aminorhodanine can be obtained by reacting aromatic aldehydes with 3′ -aminorhodanine in glacial acetic acid, with 3-arylideneminorhodanines in ammonia solution, or with 5-aryliden-3-aminorhodanines in ethanol.     

5-azo derivatives of rhodanine and its analogues in the analytical chemistry of the noble metals

Progress in the synthesis and theoretical study of the 5-azo derivatives of rhodanine, thiorhodanine, 3-aminorhodanine, thiohydantoin, pseudothiohydantoin, thiopropiorhodanine, and selenoisorhodanine is discussed. Emphasis is placed on peculiarities in the interaction of this series of reagents with noble metals and their practical application in analytical chemistry.     

UV absorption spectra of 3-aminorhodanine derivatives

3-Aminorhodanine condenses readily with isothiocyanates to form unsymmetrical thioureas of the rhodanine series. The UV spectra of arylidene derivatives of 3-aminorhodanine consist of four bands: a short-wave band with a maximum up to 242 nm, a “thioamide” band with a maximum at 264–290 nm, a “dithiocarbonate” band with maxima at 290–370 nm, and a long-wavelength K band with maxima at 310–520 nm. The K absorption band is the most characteristic band for the arylidene derivatives of 3-aminorhodanine, and the maxima for 3′,5-diarylidene derivatives are generally shifted to the short-wave region, while the maxima for the 5-monoarylidene derivatives are usually shifted to the long-wave region.     

Mass spectra of nucleoside derivatives

The mass spectra of derivatives of uridine, adenosine, cytidine and guanosine are recorded. Derivatization techniques include permethylation, acetylation, trifluoroacetylation, trimethylsilylation and the synthesis of 2′,3′-O-isopropylidenes and 2′,3′-O-phenylboronic esters. Sequential derivatization by a selective combination of some of these procedures results in nucleosides which are blocked with a characteristic group at the cis 1,2 diol position, and, which contain other substituent groups that enhance the volatility of the compound. The specific substitution at the cis-glycol region has been shown to be particularly useful in asymmetrically derivatizing dinucleoside phosphates since certain fragment ions from their mass spectra indicate the sequence of the two nucleoside components. Sequence isomers such as adenylyl-(3′-5′)-uridine and uridylyl-(3′-5′)-adenosine can be unambiguously distinguished.     

Synthesis of pyrrolo-pyrrolo-pyrazines via the Pd/C-catalyzed cyclization of N-propargyl pyrrolinyl-pyrrole derivatives

A novel and efficient synthesis of N-substituted dipyrrolo[1,2-a:2′,1′-c]pyrazine derivatives has been developed. The synthetic strategy relies on the synthesis of 4′,5′-dihydro-1H,3′H-2,2′-bipyrrole, followed by the reaction with propargyl bromide. Various substituents were introduced to the alkyne functionality using the Sonogashira coupling reaction. Aromatization of the dihydropyrrole ring followed by an intramolecular cyclization reaction between the alkyne functionality and the pyrrole nitrogen atom was catalyzed by Pd/C at high temperature to furnish the desired dipyrrolo-pyrazine skeleton.     

Improved Syntheses of Chlorodeoxynucleosides

Halodeoxynucleosides are very useful intermediates in the synthesis of nucleoside and nucleotide derivatives. Because the iodides are more reactive,¹ the corresponding chlorides have received relatively little attention although 5′-chloro-5′-deoxyadenosine (1) is effective in controlling blood pressure,² and has been employed in a novel approach to the synthesis of polynucleotides.³ Other halonucleosides have been cited as potentially important antibiotics.¹     

Synthesis of phosphorylated derivatives of isatin with sterically hindered phenol fragments

The synthesis of N-[dimethoxyphosphoryl-(3,5-di-tert-butyl-4-hydroxyphenyl)] methylisatins has been performed by the addition of isatin and 5-butylisatin to the double bond of dimethyl-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadienylidene)methylphosphonate. Subsequent functionalization of the compounds synthesized with thiosemicarbazide hydrochloride, 3-(3′,5′-di-tert-butyl-4′-hydroxyphenyl)propionic acid hydrazide, and isonicotinic acid. Hydrazide gave isatin derivatives containing several pharmacophore fragments. Each of them has the ability to the increase the antioxidant and biological activities of these compounds.     

Reactions of furocoumarins. II. Synthetic aminomethyl psoralens via chloromethylation or benzylic bromination

Several psoralen derivatives have been synthesized in order to evaluate their efficacy as photochemotherapeutic (PUVA) agents, including a variety of 4′-substituted-4,5′,8-trimethypsoralen compounds ( 1d-j ). Improved synthesis of the very potent photosensitizers 8-methylpsoralen ( 6a ) and 4,8-dimethylpsoralen ( 6b ) are described and 6a has been shown to undergo formylation in the 4′-position. Free radical bromination of 6a and 6b with NBS affords primarily 8-bromomethyl derivatives ( 8a and d ), which are readily converted into the 8-aminomethyl derivatives ( 8c and f ) by the Gabriel method. If the 4′-position is blocked, electrophilic substitution apparently occurs primarily in the 5′-position of the psoralen system. At least, chloromethylation of 4′-methylpsoralen ( 9 ) affords mainly 5′-chloromethyl derivatives ( 10a and d ), which also lead to aminomethylpsoralens ( 10c and f ).     

Phosphotungstic acid mediated,microwave assisted solvent-free green synthesis of highly functionalized 2ˈ-spiro and 2, 3-dihydro quinazolinone and 2-methylamino benzamide derivatives from aryl and heteroaryl 2-amino amides

Phosphotungstic acid has been found as green catalyst for the synthesis of spiro and cyclized quinazolinones and 2-amino substituted carboxamide under microwave irradiation and solvent-free condition has been developed. The scope of the reaction has been demonstrated for a variety of aldehydes and ketones with O-amino amides such as 2-amino-benzamide, 2-amino-5-iodo benzamide, 3-aminothiophene-2-carboxamide, 3-aminobenzofuran-2-carboxamide and 2-aminopyridine-3-carboxamides. The reaction afforded spiro-, cyclized quinazolinones and 2-amino substituted carboxamide derivatives within few minutes of irradiation in excellent yield. Plausible mechanism for the formation of products is provided. Synthetic utility of 1′H-spiro[fluorene-9,2′-quinazolin]-4′(3′H)-one 3a has been demonstrated by synthesis of 1,4-di(1′H-spiro[fluorene-9,2′-quinazolin]-4′(3′H)-one) buta-1,3-diyne 12, 1′-((1-benzyl-1H-1,2,3-triazol-4-yl) methyl)-1′H-spiro[fluorene-9,2′-quinazolin]-4′(3′H)-one 13 and 1′-phenyl-1′H-spiro[fluorene-9,2′-quinazolin]-4′(3′H)-one 14 under standard protocols.     

Synthesis of polymer intermediates containing the hexafluoroisopropylidene group via functionalization of 2,2-diphenylhexafluoropropane

The title compound was synthesized by hydrogenolysis of its precursor 2,2-bis(4-trifluoromethanesulfonatophenyl)hexafluoropropane ( 2 ) in the presence of a base. 2,2-Diphenylhexafluoropropane ( 6 ) can be appropriately functionalized at the 3,3′-positions to give the diamino ( 7 ), dibromo ( 11 ), dicarboxaldehydo ( 13 ), 3-ethynyl-3′-carboxaldehydo ( 14 ) derivatives which are important monomers in the synthesis of various high-temperatures resistant polymers and oligomers containing the hexafluoroisopropylidene (6F) group. 2,2-Bis(4-triflatophenyl)hexafluoropropane ( 2 ) undergoes quantitative dinitration at the 3,3′-positions to yield 2,2-bis(3-nitro-4-triflatophenyl)hexafluoropropane ( 3 ) which ultimately leads to the 3,3′-diamino-4,4′-bis(arylamino) ( 5 ) and 3,3′-diamino-4,4′-dihydroxy ( 8 ) derivatives which are specifically designed for phenylbenzimidazole, benzimidazoquinazoline, and benzoxazole polymers and oligomers.     

Synthesis and properties of 3-nitrosocarbazole

The synthesis of 3-nitrosocarbazole (I) by the Fischer-Hepp rearrangement of 9-nitrosocarbazole has been described. The resistance of I to oxidation provides evidence that it cannot be the intermediate in the conversion of 9-nitrosocarbazole to the C-nitro compounds. It has also been shown that I and its derivatives cannot be synthesized by the action nitrosyl chloride on carbazoles. Methylation of I yields 9-methyl-3-nitrosocarbazole, 9,9′-dimethyl-3-azocarbazole and 9,9′-dimethyl-3-azoxycarbazole as the main products. The mechanism of this disproportionation process has been proposed. The spectral data of I are given.     

Oligonucleotides and nucleotidylpeptides. XXXII. Synthesis and hydrolytic stability of amino acid derivatives of adenosine 5′-di(tri)phosphates

The synthesis has been effected of the ethyl esters of adenosine-5′-diphospho-(P_β→N)-and adenosine-5′-triphospho(P_γ→N)-alanine. It has been shown that under the conditions of synthesis the serine analogues of ATP and ADP decompose. An investigation of the hydrolytic stability of the compounds synthesized has shown that they are unstable in acid and alkaline media. In an acid medium the phosphoramide bond is cleaved more rapidly than the phosphoric anhydride bond (in the case of the ADP analogue), while in an alkaline medium the ester bond is saponified and the phosphoric anhydride bond is cleaved. The ATP analogue is more labile both in acid and in alkaline media.     

The selective acylation of the functional groups of cytidine and 2′-deoxycytidine

A study has been made of the selective acylation of cytidine and 2′-deoxycytidine derivatives. It has been shown that selective 5′-O-acetylation of 2′,3′-O-isopropylidenecytidine occurs in aqueous solutions. An improved procedure for the 4-N-acetylation of 2′-deoxycytidine is described. The benzyloxycarbonyl, methoxyacetyl and phenoxyacetyl groups have been used to protect the 4-N-position of cytidine derivatives. The first of these could be removed by hydrogenolysis over Pd—C but the use of Pt as a catalyst resulted in reduction of the cytosine ring. The other two groups could be removed by mild acidic hydrolysis. The 4-N-position of 2′,3′-O-isopropylidinecytidine and of 2′-deoxycytidine could be selectively phenoxyacetylated by the use of 2,4-dinitrophenyl phenoxyacetate.     

The triphenylmethyl (trityl) group and its uses in nucleotide chemistry

The triphenylmethyl (trityl) group can be removed from 5′-trityl 2′-deoxynucleosides (and their N-acyl derivatives) under aprotic neutral conditions without causing any side reactions. An efficient method for tritylation of N-acyl 2′-deoxynucleosides is described. Potential use of such derivatives for stepwise synthesis of deoxyoligonucleotides is discussed.     

Synthesis of 2,2′-bipyrimidine derivatives

A new total synthesis of 2,2′ -bipyrimidine derivatives by the direct condensation of 2-amidinopyrimidinebenzenesulfonate with dicarbonyl compounds is described. The following 2,2′-bipyrimidines have been prepared: 5-ethyl-4,6-dihydroxy-2,2′-bipyrimidine; 5-ethyl-4,6-dichloro-2,2 -bipyrimidine; 4,6-dihydroxy-2,2′ -bipyrimidine; 5-ethyl-4,6-dimethoxy-2,2′ -bipyrimidine.     

Synthesis of some L-idose derivatives

The synthesis of 3-0-benzyl- and 3-0-mesyl-1,2-0-isopropylidene-β′-L-iodofuranose has been effected on the basis of the intramolecular nucleophilic exchange of a mesyloxy group at C₅ in derivatives of 1,2-0-isopropylidene-α-D-glucofuranose. It has been found that in a system of vicinal primary and secondary mesyloxy groups a selective replacement of the primary mesyloxy group by an acetyl group is possible. It has been shown in benzyl and mesyl ethers of 5,6-anhydro-1,2-0 -isopropylidene-β-L-idofuranose the opening of the oxide ring under conditions of acid hydrolysis with the retention of the isopropylidene group is possible.     

Polycyclic pyridazines. II [3]. Synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrid-azine derivatives from dimethyl pyrazolo[3,4-d]pyrid-azine-5,6-dicarboxylates as the key intermediates

The synthesis of the novel pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyridazine ring system and some of its derivatives has been accomplished such as 4-amino-1-phenyl-5,8-dioxo-, 4-amino-5,8-dioxo-, 1-phenyl-5,8-dioxo-, 5,8-dioxo-, 5,8-dichloro-1-phenyl-, 5-ethoxy-1-phenyl- and 8-ethoxy-1-phenylpyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrid-azines.     

Synthesis and Characterization of New Xanthene Derivatives,and Their Electrochemical Study

This work investigated the synthesis of biphenyl‐3,3′,4,4′‐tetracarboxylic dianhydride and benzophenone‐3,3′,4,4′‐tetracarboxylic dianhydride derivatives ( 3a – e and 6a – e ) with different substituted phenols via Friedel‐Crafts acylation reaction in the presence of dilute sulfuric acid. Dianhydride derivatives with 3‐N,N′‐dimethylamino phenol ( 3d and 6d ) and resorcinol ( 3e and 6e ) have been found to be highly fluorescent. The structures of all newly synthesized compounds were confirmed by the chromatographic, spectral and elemental data. Electrochemical study was done to determine to band gap energy, LUMO and HOMO levels energy. Band gap and LUMO energy levels were found to be lowest in xanthene derivatives substituted with 3‐N,N′‐dimethylamino group having value 2.24 and 4.85 eV respectively.     

Study of the Synthesis of Dextran Derivatives

Abstract

The synthesis of biologically active high-molecular compounds offers an interesting subject for study in polymer chemistry. Dextran, one of the best blood plasma expanders, is a good product for use in synthesizing biologically active water-soluble polymers. This paper discusses the synthesis of water-soluble derivatives of dextran which can be used as drug carriers or as independent physiologically active compounds. The synthesis of these derivatives involved oxidation of dextran, O-alkylation of dextran, subsequent transformation of ethers of dextran containing reactive functional groups, and graft polymerization. Periodate oxidation of dextran resulted in the production of a derivative of dextran containing aldehyde groups: dialdehydedextran. Subsequent oxidation of dialdehyde-dextran with sodium chlorite permitted the introduction of carboxyl groups into the macromolecule of dextran. In order to introduce sulfonic acid, phosphonic, mercapto, chlorhydrinic, cyano, and aromatic amino groups into the macromolecule of dextran, dextran was alkylated with various alkylating reagents. The synthesized products were sulfopropyl, phosphonomethyl, mercaptoethyl, 3-chloro-2-hydroxypropyl, cyanoethyl, and 2-(3′-amino-4′-methoxyphenyl)-sulfonylethyl ethers of dextran. Treatment of the 3-chloro-2-hydroxypropyl ether of dextran with ammonia, amines, and aliphatic and aromatic amino acids produced ethers of dextran containing primary, secondary, and tertiary amino groups and quaternary ammonium groups, as well as residual aliphatic and aromatic amino acids.

Cyanethyl ether of dextran was used to synthesize derivatives of dextran containing thioamide and hydrazidine groups.

Graft copolymers of dextran and polyacrylic acid and of dextran and poly-2-methyl-5-vinylpyridine were synthesized. Redox systems were utilized to initiate graft copolymerizatLon with tetravalent cerium compounds used as oxidants and pentavalent vanadium with dextran or 2-(3′-amino-4′-methoxyphenyl)-sulfonylethyl ether of dextran used as reductant. This method produced graft copolymers with short graft chains.

The availability of the above derivatives of dextran has permitted the linking of drugs to dextran by different types of chemical bonds.