2,4‐Di­nitro­phenyl­hydrazones of 2,4‐di­hydroxy­benz­aldehyde, 2,4‐di­hydroxy­aceto­phenone and 2,4‐di­hydroxy­benzo­phenone

In 2,4‐di­hydroxy­benz­aldehyde 2,4‐di­nitro­phenyl­hydrazone N,N‐di­methyl­form­amide solvate {or 4‐[(2,4‐di­nitro­phenyl)­hydrazono­methyl]­benzene‐1,3‐diol N,N‐di­methyl­form­amide solvate}, C₁₃H₁₀N₄O₆·C₃H₇NO, (X), 2,4‐di­hydroxy­aceto­phenone 2,4‐di­nitro­phenyl­hydrazone N,N‐di­methyl­form­am­ide solvate (or 4‐{1‐[(2,4‐di­nitro­phenyl)hydrazono]ethyl}benzene‐1,3‐diol N,N‐di­methyl­form­amide solvate), C₁₄H₁₂N₄O₆·C₃H₇NO, (XI), and 2,4‐di­hydroxy­benzo­phenone 2,4‐di­nitro­phenyl­hydrazone N,N‐di­methyl­acet­amide solvate (or 4‐­{[(2,4‐di­nitro­phenyl)hydrazono]phenyl­methyl}benzene‐1,3‐diol N,N‐di­methyl­acet­amide solvate), C₁₉H₁₄N₄O₆·C₄H₉NO, (XII), the molecules all lack a center of symmetry, crystallize in centrosymmetric space groups and have been observed to exhibit non‐linear optical activity. In each case, the hydrazone skeleton is fairly planar, facilitated by the presence of two intramolecular hydrogen bonds and some partial N—N double‐bond character. Each molecule is hydrogen bonded to one solvent mol­ecule.     

2,4-Bis(4-methylpheylthio)-1,3,2λ5,4λ5-dithiadiphosphetan-2,4-dithion: Ein neues Reagens zur Schwefelung von N,N-disubstituierten Amiden

2,4-Bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione: A New Reagent for Thiation of N,N-Disubstituted Amides As a new reagent for the thiation of amides, the easily accessible 2,4-bis(4-methylphenylthio)-1,3,2λ⁵,4λ⁵-dithiadiphosphetane-2,4-dithione ( 9 ) shows a remarkable selectivity. This selectivity – the preferred thiation of N,N-disubstituted amides – is complementary to the one of the well known Lawesson reagent. Thiation of diamides of type 2 with 9 leads via cyclization of the corresponding dithiodiamides to 1,3-thiazole-5(4H)-thiones 1 (Scheme 3).     

4,6-Dimethylpyridine-2,3-dicarbonitrile and its reaction with <Emphasis Type="Italic">N</Emphasis>-acylhydrazines

An efficient method has been developed for the synthesis of 4,6-dimethylpyridine-2,3-dicarbonitrile. A study was carried out on the reaction of this compound with N-acylhydrazines to give two structural isomers, namely, N′-(7-amino-2,4-dimethyl-5H-pyrrolo[3,4-b]pyridin-5-ylidene)carbohydrazides and N′-(5-amino-2,4-dimethyl-7H-pyrrolo[3,4-b]pyridin-7-ylidene)carbohydrazides as well as disubstituted N′,N″-(2,4-dimethyl-5H-pyrrolo[3,4-b]pyridine-5,7-diylidene)dicarbohydrazides.     

N-vinyl carbazole copolymers

The synthesis of N-vinyl carbazole (VCbz) copolymers, some of which contain electron-accepting groups, is described. The new copolymers are: copoly[N-vinyl carbazole-di(2-N-carbazylethyl)-fumarate](II); copoly(N-vinyl carbazole-vinyl-2,4-dinitrobenzene-sulfonate)(IV); copoly(N-vinyl carbazole-vinyl-2,4-dinitrobenzene-sulfenate)(V); copoly(n-butyl acrylate-t-butyl peracrylate)(VII); copoly(n-butyl acrylate-t-butyl acrylate-graft-N-vinyl carbazole)(VIII).     

Synthesis of the penta-glutamyl derivative of N-[4-[N-[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)-propyl]amino]benzoyl]-L-glutamic acid (5-DACTHF). An acyclic analogue of tetrahydrofolic acid

The penta-glutamyl derivative of N-[4-[N-[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]amino]-benzoyl)-L-glutamic acid (1, 5-DACTHF, 543U76) was synthesized by a convergent route. L-γ-Glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-glutamic acid heptakis t-butyl ester ( 20 ) was prepared in ten steps from L-glutamic acid di-t-butyl ester and N-(benzyloxycarbonyl)-L-glutamic acid α-t-butyl ester. 4-[N-[3-(2,4-Diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]trifluoroacetamido]benzoic acid ( 6 ), which was synthesized from pyrimidinylpropionaldehyde 3 in three steps, was condensed with 20 , followed by deprotection to provide N-[4-[N-[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]amino]benzoyl]-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-γ-glutamyl-L-glutamic acid ( 2 ). Hexaglutamate 2 is a potent inhibitor of glycinamide ribonucleotide transformylase.     

Reactions of N- and C-Alkenylanilines: V. Synthesis of Iodo-Substituted Heterocycles from o-Cycloalkenylanilines and Their Transformations

Iodination of N-isopropyl- and N-benzyl-2-(2-cyclohexenyl)anilines gave the corresponding 1-iodo-hexahydrocarbazoles which underwent quantitative isomerization into 3-iodo-2,4-propano-1,2,3,4-tetrahydro-quinolines. Nucleophilic substitution in 1-iodohexahydrocarbazoles and 3-iodo-2,4-propano-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole was studied. N-Allylation of the latter via reaction with allyl bromide is accompanied by replacement of the iodine atom by bromine.     

2,4-DIMETHOXYBENZYL: AN AMIDE PROTECTING GROUP FOR 2-ACETAMIDO GLYCOSYL DONORS[1]

2,4-Dimethoxybenzyl (Dmob) was used as an amide protecting group for 2-acetamido glycosyl donors. The N-Dmob group was introduced by imine formation between 2,4-dimethoxybenzaldehyde and d-glucosamine, followed by per-O-acylation, reduction to form the amine, and finally N-acetylation to give 1,3,4,6-tetra-O-acetyl-2-deoxy-2-(2,4-dimethoxybenzylacetamido)-β-D-glucopyranose. Selective 1-O-deacetylation and treatment with trichloroacetonitrile gave the corresponding trichloroacetimidate glycosyl donor. Lewis acid-promoted glycosylations of the model substrate 3-nitrobenzyl alcohol gave exclusively the β-glycoside product, either with or without the Dmob protecting group remaining depending on the reagent and conditions employed. The N-Dmob protected 1-O-acetate glucosyl donor gave higher glycosylation yields than the corresponding 2-acetamido glucosyl donor without Dmob protection.     

Synthesis and properties of polyurethanes containing s-triazine rings in the main chain

Eight new diisocyanate monomers containing s-triazine ring have been prepared from the parent diacids via the Curtius rearrangement of the corresponding diacyl azides. The parent diacids were synthesised by the reaction of p- and m-hydroxybenzoic acid with 6-methoxy-2,4-dichloro-s-triazine, 6-phenoxy-2,4-dichloro-s-triazine, 6-phenyl-2,4-dichloro-s-triazine, and 2-diphenylamino-4,6-dichloro-s-triazine respectively. Polyurethanes have been synthesised by solution polymerization of these diisocyanates with ethylene glycol in N,N-dimethylacetamide (DMAC). The resulting polymers were characterized by IR spectroscopy, viscosity measurement, solubility tests, and softening points.     

Synthesis of 3-substituted N-aminopyridinium salts

Ring opening of N-(2,4-dinitrophenyl)pyridinium chlorides with hydrazine followed by recyclization resulted in the formation of N-aminopyridinium salts. The scope of this reaction sequence was determined and several new 3-substituted N-aminopyridinium salts were prepared.     

One barbiturate and two solvated thiobarbiturates containing the triply hydrogen‐bonded ADA/DAD synthon,plus one ansolvate and three solvates of their coformer 2,4‐diaminopyrimidine

A path to new synthons for application in crystal engineering is the replacement of a strong hydrogen‐bond acceptor, like a C=O group, with a weaker acceptor, like a C=S group, in doubly or triply hydrogen‐bonded synthons. For instance, if the C=O group at the 2‐position of barbituric acid is changed into a C=S group, 2‐thiobarbituric acid is obtained. Each of the compounds comprises two ADA hydrogen‐bonding sites (D = donor and A = acceptor). We report the results of cocrystallization experiments of barbituric acid and 2‐thiobarbituric acid, respectively, with 2,4‐diaminopyrimidine, which contains a complementary DAD hydrogen‐bonding site and is therefore capable of forming an ADA/DAD synthon with barbituric acid and 2‐thiobarbituric acid. In addition, pure 2,4‐diaminopyrimidine was crystallized in order to study its preferred hydrogen‐bonding motifs. The experiments yielded one ansolvate of 2,4‐diaminopyrimidine (pyrimidine‐2,4‐diamine, DAPY), C₄H₆N₄, (I), three solvates of DAPY, namely 2,4‐diaminopyrimidine–1,4‐dioxane (2/1), 2C₄H₆N₄·C₄H₈O₂, (II), 2,4‐diaminopyrimidine–N,N‐dimethylacetamide (1/1), C₄H₆N₄·C₄H₉NO, (III), and 2,4‐diaminopyrimidine–1‐methylpyrrolidin‐2‐one (1/1), C₄H₆N₄·C₅H₉NO, (IV), one salt of barbituric acid, viz. 2,4‐diaminopyrimidinium barbiturate (barbiturate is 2,4,6‐trioxopyrimidin‐5‐ide), C₄H₇N₄⁺·C₄H₃N₂O₃⁻, (V), and two solvated salts of 2‐thiobarbituric acid, viz. 2,4‐diaminopyrimidinium 2‐thiobarbiturate–N,N‐dimethylformamide (1/2) (2‐thiobarbiturate is 4,6‐dioxo‐2‐sulfanylidenepyrimidin‐5‐ide), C₄H₇N₄⁺·C₄H₃N₂O₂S⁻·2C₃H₇NO, (VI), and 2,4‐diaminopyrimidinium 2‐thiobarbiturate–N,N‐dimethylacetamide (1/2), C₄H₇N₄⁺·C₄H₃N₂O₂S⁻·2C₄H₉NO, (VII). The ADA/DAD synthon was succesfully formed in the salt of barbituric acid, i.e. (V), as well as in the salts of 2‐thiobarbituric acid, i.e. (VI) and (VII). In the crystal structures of 2,4‐diaminopyrimidine, i.e. (I)–(IV), R₂²(8) N—H…N hydrogen‐bond motifs are preferred and, in two structures, additional R₃²(8) patterns were observed.     

Synthesis of 2,4‐diaminothieno‐ and pyrrolo[2,3‐d]pyrimidine‐6‐carboxylic acid derivatives

A series of new 2,4‐diaminothieno[2,3‐d]‐ and 2,4‐diaminopyrrolo[2,3‐d]pyrimidine derivatives were synthesised. Reaction of 2‐amino‐4,6‐dichloropyrimidine‐5‐carbaldehyde ( 1 ) with ethyl mercaptoacetate, methyl N‐methylglycinate or ethyl glycinate afforded ethyl (2‐amino‐4‐chloro‐5‐formylpyrimidin‐6‐yl)thioacetate ( 2a ), methyl N‐(2‐amino‐4‐chloro‐5‐formylpyrimidin‐6‐yl)‐N‐methylglycinate ( 2b ) and ethyl N‐(2‐amino‐4‐chloro‐5‐formylpyrimidin‐6‐yl)glycinate ( 2c ), respectively. Compounds 2a,b by treatment with bases cyclised to the corresponding 2‐amino‐4‐chlorothieno‐ and pyrrolo[2,3‐d]pyrimidine‐6‐carboxylates ( 3a,b ). Heating 2,4‐diamino‐6‐chloropyrimidine‐5‐carbaldehyde ( 5 ) with ethyl mercaptoacetate or methyl N‐methylglycinate gave 2,4‐diaminothieno[2,3‐d]‐ and 2,4‐diaminopyrrolo[2,3‐d]‐pyrimidine‐6‐carboxylates ( 6a,b ), whereas compound 5 with ethyl glycinate under the same reaction conditions afforded ethyl N‐(2,4‐diamino‐5‐formylpyrimidin‐6‐yl)glycinate ( 7 ). Treatment of 2,4‐diaminothieno[2,3‐d]pyrimidine‐6‐carboxylic acid ( 8a ) with 4‐methoxy‐, 3,4,5‐trimethoxyanilines or ethyl N‐(4‐aminobenzoyl)‐L‐glutamate in the presence of dicyclohexylcarbodiimide and 1‐hydroxybenzotriazole furnished the corresponding N‐arylamides 9‐11.     

p-(5-Fluor-2,4-dinitro-1-phenylazo)-N,N-dimethylanilin,ein neues Reagens zur flüssigchromatographischen Bestimmung von Phenolen

The synthesis ofp-(5-fluoro-2,4-dinitro-1-phenylazo)-N,N-dimethylaniline and its reactions with phenoles top-(2,4-dinitro-5-phenoxy-1-phenylazo)-N,N-dimethylanilines and the use of the resulting coloured products for the TLC determination of phenoles is described.

     

Structure of 2,4-Dihydrobenzylidene- and 5-Bromo-2-hydroxybenzylidene(methyl)amine N-Oxides

2,4-Dihydroxybenzylidene(methyl)amine and 5-bromo-2-hydroxybenzylidene(methyl)amine N-oxides were synthesized by condensation of N-methylhydroxylamine with the corresponding aldehydes. Their crystal structures were solved by X-ray analysis.     

Preparation and polymerization of a sugar dithiol

2,4-O-Benzylidene-1,6-dithiol-D-glucitol is prepared by nucleophilic displacement of tosyloxy groups from 3,5-di-O-acetyl-2,4-O-benzylidene-1,6-di-O-tosyl-D-glucitol with thioacetate in N,N-dimethylformamide and deacetylation of the product. Oxidative polymerization with oxygen and selenium dioxide produces film-forming disulfide polymers with intrinsic viscosities up to 0.41. Other oxidizing agents produce polymers of lower viscosity. Condensation of the dithiol with benzaldehyde also gives polymers of low viscosity.     

SYNTHESIS OF 2,4-DISUBSTITUTED NORTROPINONE DERIVATIVES BY ALDOL CONDENSATION

2,4-Disubstituted nortropinone derivatives 2, with anticipated anticonvulsant activity, were synthesized by the reaction of N-substituted nortropinones, ethanol, 5N-NaOH, and aromatic aldehydes (R₁CHO).     

Calcium‐containing poly(urethane‐urea)s: Synthesis,spectral, and thermal studies

A calcium salt of mono(hydroxypentyl)phthalate [Ca(HPP)₂] was synthesized by the reaction of 1,5‐pentanediol, phthalic anhydride, and calcium acetate. Four different bisureas such as hexamethylene bis(ω,N‐hydroxyethylurea), tolylene 2,4‐bis(ω,N‐hydroxyethylurea), hexamethylene bis(ω,N‐hydroxypropylurea), and tolylene 2,4‐bis(ω,N‐hydroxypropylurea) were prepared by reacting ethanolamine or propanolamine with hexamethylene diisocyanate (HMDI) or tolylene 2,4‐diisocyanate (TDI). Calcium‐containing poly(urethane‐urea)s (PUUs) were synthesized by reacting HMDI or TDI with 1:1 mixtures of Ca(HPP)₂ and each of the bisureas with di‐n‐butyltin dilaurate as a catalyst. The PUUs were well characterized by Fourier transform infrared spectroscopy, ¹H and ¹³C NMR, solid‐state ¹³C–cross‐polarization/magic‐angle spinning NMR, viscosity, solubility, elemental analysis, and X‐ray diffraction studies. Thermal properties of the polymers were also examined with thermogravimetric analyses and differential scanning calorimetry. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1809–1819, 2004     

Synthesis and antimalarial activity of a series of 2,4-diamino-6-[(N-alkylanilino)methyl]quinazolines

A series of 2,4-diamino-6-[(N-alkylanilino)methyl]quinazolines were prepared by bromination of 2,4-dibenz-amido-6-methylquinazoline followed by treatment with secondary arylamines and deblocking with base. A variety of analogs demonstrated substantial activity against Plasmodium berghei infections in mice.     

Synthesis and antifolate activity of new pyrrolo[2,3‐d]pyrimidine and thieno[2,3‐d]pyrimidine inhibitors of dihydrofolate reductase

Three previously undescribed dihydrofolate reductase (DHFR) inhibitors, N^α‐[4‐[N‐[(2,4‐diaminopyrrolo[2,3‐d]pyrimidin‐5‐yl)methyl]amino]benzoyl]‐N^δ‐hemiphthaloyl‐L‐ornithine (7) , N^α‐ [4‐ [N‐[(2,4‐diaminothieno[2,3‐d]pyrimidin‐5‐yl)methyl]amino]benzoyl]‐ N^δ‐hemiphthaloyl‐L‐ornithine (8) , and N‐[4‐[N‐[(2,4‐diaminothieno[2,3‐d]pyrimidin‐5‐yl)methyl]amino]benzoyl]‐L‐glutamic acid (12) , were synthesized and their antifolate activity was assessed. The ability of 7 and 8 to bind to DHFR and inhibit the growth of CCRF‐CEM human lymphoblastic leukemia cells in culture were dramatically reduced in comparison with the corresponding pteridine analogue, N^α‐(4‐amino‐4‐deoxypteroyl)‐N^δ‐hemiphmaloyl‐L‐ornithine ( 1 , PT523). In a similar manner, the antifolate activity of 12 was markedly reduced in comparison with that of the corresponding glutamate analogue, aminopterin ( 5 , AMT). In contrast, 7, 8 , and 12 all displayed excellent affinity for the reduced folate carrier (RFC) of CCRF‐CEM cells as measured by a standard competitive influx assay. Lack of a consistent correlation between the results of the growth inhibition assays and those of the DHFR and RFC binding assays results suggest that additional factors also play a role in the antifolate activity of these compounds.     

Synthesis of Nonsymmetrically N,N′‐Diaryl‐Substituted 4,4′‐Bipyridinium Salts with Redox‐Tunable and Titanium Dioxide (TiO2)‐Anchoring Properties

A general method for the synthesis of so far unknown nonsymmetrically substituted N‐aryl‐N′‐aryl′‐4,4′‐bipyridinium salts is presented (Scheme 1). The common intermediate in all procedures is N‐(2,4‐dinitrophenyl)‐4,4′‐bipyridinium hexafluorophosphate ( 1 ⋅ ). For the synthesis of nonsymmetric arylviologens, 1 ⋅ was arenamine‐exchanged by the Zincke reaction, and then activated at the second bipyridine N‐atom with 2,4‐dinitrophenyl 4‐methylbenzenesulfonate. The detailed preparation of the six N‐aryl‐N′‐aryl′‐viologens 21 – 26 is discussed (Scheme 2). The generality of the procedure is further exemplified by the synthesis of two nonsymmetrically substituted N‐aryl‐N′‐benzyl‐ (see 11 and 12 ), and seven N‐aryl‐N′‐alkyl‐4,4′‐bipyridinium salts (see 28 – 34 ) including substituents with metal oxide anchoring and redox tuning properties. The need for these compounds and their usage as electrochromic materials, in dendrimer synthesis, in molecular electronics, and in tunable‐redox mediators is briefly discussed. The latter adjustable property is demonstrated by the reduction potential measured by cyclic voltammetry on selected compounds (Table).     

Folic acid analogs. III. N-(2-[2-(2,4-diarnino-6-quinazolinyl)ethyl]benzoyl)-l-glutamic acid

A trideaza analog of aminopterin, N-(4[2-(2,4-diamino-6-quinazolinyl)ethyl]benzoyl)-L-glutamic acid, was prepared by a Wittig condensation of 2,4-diaminoquinazoline-6-carboxaldehyde and [P-(N-[1,3-bis(ethoxycarbonyl)propan-1-yl]aminocarbonyl)phenylmethyl]triphenylphosphonium bromide followed by catalytic reduction and mild hydrolysis. This compound was found to have confirmed inhibitory activity against leukemia L1210 in mice.