Synthesen mit 1,3-Dithietanen. IX [1]. Reaktionen des 2,4-Bis-(äthoxycarbonyl-cyan-methylen)-1,3-dithietans und des 2-Cyan-3,3-bis-(methylmercapto)-acrylsäureäthylesters mit Carbonsäurehydraziden

Syntheses with 1,3-Dithietanes. IX. Reactions of 2,4-Bis(ethoxycarbonyl-cyano-methylene)-1, 3-dithietane and of Ethyl 2-cyano-3, 3-bis(methylmercapto)acrylate with Carboxylic Acid Hydrazides 2, 4-Bis(ethoxycarbonyl-cyano-methylene)-1, 3-dithietane 1 reacts with carboxylic acid hydrazides to yield ethyl 1-aroyl-5-imino-3-mercapto-Δ³-pyrazoline-4-carboxylates 4. 4 and hydrazin hydrate yield ethyl 1-aroyl-5-imino-3-hydrazino-Δ³-pyrazoline-4-carboxylates 5 which are transformed by heat to the ethyl 3(5)-amino-5(3)-(2-aroyl-hydrazino)pyrazole-4-carboxylates 6 . The reaction of ethyl 2-cyano-3,3-bis(methylmercapto)acrylate 8 with carboxylic acid hydrazides yield ethyl 1-aroyl-3-amino-5-methylmercapto-pyrazole-4-carboxylates 10 . Compounds 10 are compared with S-methyl derivatives of 4 .     

The current dye intermediate market – A cautionary tale and detective story; characterization and unambiguous synthesis of 5-amino-4-chloro-2,7-dimethyl-1H-benzimidazole

Commercially delivered 2-chloro-5-methyl-1,4-phenylenediamine (1 metric ton) was not identical to the commonly used dye intermediate; it was found that the material was a pure but not yet described molecule. ¹H, ¹³C NMR, MS, microanalysis and X-ray diffraction showed that the substance was in fact 5-amino-4-chloro-2,7-dimethyl-1H-benzimidazole. The manufacturer's mistake was explained by independent synthesis, which revealed that the key step was nitration of N-(5-chloro-2-methyl-4-nitrophenyl)acetamide giving N-(5-chloro-2-methyl-4,6-dinitrophenyl)acetamide, which requires Fe(III) catalysis. Subsequent reduction of N-(5-chloro-2-methyl-4,6-dinitrophenyl)acetamide with hydrogen and Pd/C catalyst exclusively gives N-(2,4-diamino-3-chloro-6-methylphenyl)acetamide. The ring closure reaction giving 5-amino-4-chloro-2,7-dimethyl-1H-benzimidazole takes place during the reduction with iron.     

The Chichibabin Amination of 5-Phenylpyrimidine and Phenylpyrazine [1,2]

5-Phenylpyrimidine ( 1 ) on treatment by KNH₂/NH₃, affords a mixture of 2 amino- and 4-amino-5-phenylpyrimidine. The presence of only the anionic C-4 adduct. 4-amino-5-phenyl-1 (or 3), 4-dihydropyrimidinide was shown by ¹H- and ¹³C-NMR spectroscopy of a solution of 1 in KNH₂/NH₃. Study of the amination by use of ¹⁵N-labelled KNH₂/NH₃ convincingly shows that in the formation of the 2-amino compound a ring opening-ring closure sequence is involved. The amination of phenylpyrazine ( 11 ) into 5-amino- and 3-amino-2-phenylpyrazine has been found to occur without opening of the pyrazine ring. Examination by ¹H- and ¹³C-NMR spectroscopy of a solution of 11 in KNH₂/NH₃, reveals that at −60°C three adducts are present; i.e. 3-amino-, 5-amino- and 6-amino-2-phenyl-dihydropyrazinides, at −40°C the C-3 and C-5 adducts are formed; and at room temperature only the thermodynamically most stable C-5 adduct is present.     

Spectrophotometric assay of 2,4-dienoyl coenzyme a reductase with 5-phenyl-2,4-pentadienoyl-coenzyme a as substrate

The spectrophotometric assay of 2,4-dienoyl coenzyme A (CoA) reductase (EC 1.1.1.34) was modified to improve the linearity and sensitivity of this method. 5-Phenyl-2,4-pentadienoyl-CoA, which has an absorbance maximum at 340 nm with an extinction coefficient of 44,300 M⁻¹ cm⁻¹, was synthesized and used as substrate. This compound is reduced by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent 2,4-dienoyl-CoA reductase to 5-phenyl-3-pentenoyl-CoA. When a tissue homogenate serves as an enzyme source, the product is further metabolized by Δ³Δ²-enoyl-CoA isomerase (EC 5.3.3.8) to 5-phenyl-2-pentenoyl-CoA, which is hydrated to 5-phenyl-3-hydroxypentanoyl-CoA by enoyl-CoA hydratase (EC 4.2.1.17). The modified assay method, which measures the decrease in absorbance at 340 nm due to the reduction of 5-phenyl-2,4-pentadienoyl-CoA and the oxidation of NADPH, is linear for a longer period of time and is twice as sensitive as the conventional assay with 2,4-decadienoyl-CoA as substrate.     

Reaction of 6-amino-5-nitrosouracil with thiourea: Structure of the hydrolysis product

The interaction of 6-amino-5-nitrosouracil with thiourea in aqueous acidic solution results in the 6-amino-5-formamidinosulfenimino-2,3,4,5-tetrahydropyrimidine-2,4-dione di-p-toluenesulfonate that is subjected to hydrolysis with the formation of 5-formamidinosulfeniminobarbituric acid p-toluenesulfonate monohydrate.     

Untersuchungen zur Iodierung von 4-Amino-2,6-dimethyl-pyrimidinen – eine Möglichkeit zur regiospezifischen Funktionalisierung

Studies on the Iodination of 4-Amino-2,6-dimethylpyrimidine — A Possibility of the Regiospecific Functionalization The iodination of 4-amino-2,6-dimethyl-pyrimidine 1a with I₂/H₂SO₄/H₂O/H₂O₂ does not give, as supposed hitherto, the 5-iodo derivative ( 2 ) but affords the corresponding 2-iodomethyl derivative 3a . The reaction pathway of the iodination is discussed. The reaction of 3a with nucleophiles leads to a variety of side chain-substituted pyrimidines 5a – j .     

Synthesis and Study of Multifunctional Cyclodextrin–Deferasirox Hybrids

Metal dyshomeostasis is central to a number of disorders that result from, inter alia, oxidative stress, protein misfolding, and cholesterol dyshomeostasis. In this respect, metal deficiencies are usually readily corrected by treatment with supplements, whereas metal overload can be overcome by the use of metal-selective chelation therapy. Deferasirox, 4-[(3Z,5E)-3,5-bis(6-oxo-1-cyclohexa-2,4-dienylidene)-1,2,4-triazolidin-1-yl]benzoic acid, Exjade, or ICL670, is used clinically to treat hemosiderosis (iron overload), which often results from multiple blood transfusions. Cyclodextrins are cyclic glucose units that are extensively used in the pharmaceutical industry as formulating agents as well as for encapsulating hydrophobic molecules such as in the treatment of Niemann–Pick type C or for hypervitaminosis. We conjugated deferasirox, via an amide coupling reaction, to both 6^A-amino-6^A-deoxy-β-cyclodextrin and 3^A-amino-3^A-deoxy-2^A(S),3^A(S)-β-cyclodextrin, at the upper and lower rim, respectively, creating hybrid molecules with dual properties, capable of both metal chelation and cholesterol encapsulation. Our findings emphasize the importance of the conjugation of β-cyclodextrin with deferasirox to significantly improve the biological properties and to decrease the cytotoxicity of this drug.     

Adsorption of 2,4-D on Mg/Al–NO3 layered double hydroxides with varying layer charge density

Layered double hydroxides (LDHs) have high surface area and high anion exchange capacity, so they have been proposed to be an effective scavenger for contaminants. In this study, the adsorption of 2,4-dichlorophenoxyacetate (2,4-D) on Mg/Al–NO₃ LDHs with varying layer charge density was investigated with particular attention on the effect of the orientation of the interlayer nitrate. Three Mg/Al LDHs were synthesized with Al³⁺/(Al³⁺ + Mg²⁺) molar ratios of 3.3 (LDH3), 2.6 (LDH4) and 2.1 (LDH5). The results of adsorption experiments showed that LDH5 exhibited an S-type isotherm with a low 2,4-D adsorption capacity due to the low accessibility of 2,4-D to the interlayer space. The accessibility was restricted by the small basal spacing of LDH5 as a result of the parallel orientation of the interlayer nitrate with respect to the hydroxide sheet. Thus, the 2,4-D adsorption occurred mainly on the external surface of the material. On the contrary, LDH3, which has the highest layer charge density among the samples, contains nitrate with an orientation perpendicular to the hydroxide sheet of LDH3. The interlayer nitrate was readily exchanged by 2,4-D. Thus, in addition to the adsorption on the external surface, the replacement of the interlayer nitrate by 2,4-D contributed to a higher adsorbed amount of 2,4-D; the 2,4-D adsorption of LDH3 exhibited an L-type isotherm. For LDH4 that contained interlayer nitrate with both parallel and perpendicular orientations, the adsorption characteristics were between those of LDH3 and LDH5. This work has demonstrated the dependence of 2,4-D adsorption characteristics on the nitrate orientation in LDHs, as a consequence of changing layer charge density.     

Synthesis and characterization of novel self doping water soluble polynaphthylamines

The oxidative polymerization of 5-amino-1-naphthyloxy acetic acid, 5-amino-1-naphthyloxydifluro acetic acid and 3-(5-aminonaphthyloxy)-1-propanesulfonic acid was achieved with reasonable yield (30-56%), and modest electrical conductivity (10⁻⁴-10⁻⁵ S/cm). The sodium salts of the polymers are soluble in water and exhibit fluorescence.     

Thiatriazole. VII. 3-Aroxy-5-imino-1,2,4-dithiazole aus 5-Amino-1,2,3,4-thiatriazol

Thiatriazoles. VII. 3-Aroxy-1,2,4-dithiazole-5-imids of 5-Amino-1,2,3,4-thiatriazole The unstable but isolable 3-aroxy-1,2,4-dithiazole-5-imids ( 2a – d ) has been found on chlorothioformate acylation of 5-amino-1,2,3,4-thiatriazole ( 1 ) in acetonitril. Further acylation and nucleophilic displacement reactions gave stable 3-amino-5-acylimino-1,2,4-dithiazoles ( 6a – c , 7 ). The structure of the prepared compounds was inferred from their ¹H and ¹³C-n.m.r., mass spectra and corroborated by comparison with the data of similar derivates as well as by chemical means.     

13C-NMR-Untersuchungen an 4-Amino-2,6-dialkyl-pyrimidinen und ihren Sulfonamidderivaten

Carbon-13 N.M.R. Studies on 4-Amino-2,6-dialkyl Pyrimidines and Their Sulfonamide Derivatives Carbon-13 n.m.r. studies on 4-amino-2,4-dialkyl pyrimidines and their sulfonamide derivatives have shown that the known additivity rules for the assignment of signals are not valid. The reason is a tautomerism as demonstrated by changes of the chemical shifts of the alkyl groups. The electronic influence of substituents at the amino group on the alkyl C-atoms are neglegible compared to changes due to tautomerism.     

Soil transformation of wheat and corn metabolites mboa and DIM2BOA into aminophenoxazinones

The defensive cyclic hydroxamates 7-methoxy-2,4-dihydroxy-1,4(2H)-benzoxazin-3-one (DIMBOA) and 7,8-dimethoxy-2,4-dihydroxy-1,4(2H)-benzoxazin-3-one (DIM₂BOA) of wheat and corn are transformed in nonsterile soil, via 6-methoxy-2(3H)-benzoxazolone (MBOA) and 6,7-dimethoxy-2(3H)-benzoxazolone (M₂BOA) respectively, into 2-amino-7-methoxy-3H-phenoxazin-3-one and 2-amino-4,6,7-trimethoxy-3H-phenoxazin-3-one. The soil transformation is similar of that undergone by the rye metabolite 2(3H)-benzoxazolone (BOA) into 2-amino-3H-phenoxazin-3-one. The transformations to phenoxazinones are not observed in sterile soil. The 2-amino-3H-phenoxazin-3-one inhibits barnyard grass radicle elongation, but the methoxylated aminophenoxazinones are not significantly inhibitory.     

Synthese von 6-(pyrid-4-yl)-substituierten Pyrido[: 3-d]pyrimidinen und 1,8-Naphthyridinen

Synthesis of 6-(4-pyridinyI)-substituted Pyrido[2,3-d]pyrimidines and 1,8-Naphthyridinms A series of new 6-(4-pyridinyl)-substituted pyrido-[2,3-d]pyrimidines 2 – 4 and 1,8-naphthyridines 6 , respectively, is described. Cyclisation of 2-amino-5-(4-pyridinyl)-pyridinm-3-carboxamide 1a with diethyl oxalate gives the pyrido-[2,3-d]pyrimidinm 2a . Alkylation of( 2a ) yields the 3-ethylaminoxyrido[2,3-d]pyrimidine derivative 2b . Saponification of 2a , b gives the corresponding carboxylic acids 3a , b , which are decarboxylated by heating above the melting point to give 4a , b . The 2-amino-5-(4-pyridinyl)-pyridinm carboxylic acid derivatives 1 b – e react with ethylmalonylchloridm and diethyl malonate to afford the 1,8-naphthyridines 6b – e . The 1-oxide 7 in a similar reaction gives 8 and the oxdiazole( 9 ) which is converted by ring transformation to the 1,8-naphthyridine 10 .     

Synthesis of pyrazolo[4′,3′:5,6]pyrazino[2,3-c]pyrazoles and pyrazolo[4′,3′:5,6]pyrazino[2,3-d]pyrimidines and their application to polyester fibres

4-Nitroso-1-phenyl-3-methyl-5-aminopyrazole ( 1 ) was condensed with ethylcyanoacetate ( 2 ), malononitrile ( 4a ) and 2-cyanomethylbenzimidazole ( 4b ) to yield 6-hydroxy-5-cyano, 6-amino-5-cyano and 6-amino-5-(benzimidazol-2-yl)-3-methylpyrazolo [3,4-b]pyrazines 3, 5a and 5b , respectively. 5-Cyano-6-chloro derivative 6 obtained from 3 was converted to 3-aminopyrazolo[4′,3′:5,6]pyrazino[2,3-c]pyrazoles 8a and 8b by the treatment with hydrazin hydrate ( 7a ) and phenylhydrazine ( 7b ), respectively. Compound 5a was treated with formamide ( 9a ), urea ( 9b ) and thiourea ( 9c ) to give 4-aminopyrazolo[4′,3′:5,6]pyrazino[2′3′-d]pyrimidines 10a–10c. With refluxing acetic anhydride compounds 8a, 8b and 10a gave corresponding acetamido derivatives 8c, 8d and 10d. Compound 5a was treated with ethylorthoformate ( 11 ), acetic anhydride ( 12 ) or benzoylchloride ( 13 ) to give fused benzimidazopyrazolo[4′,3′:5,6]pyrazino[2′,3′-d]pyrimidines, viz., benzimidazol[1,2-c]pyrazolo[4,3-g]pteridines ( 14a–14c ). Some of the compounds 8, 10 and 14 were applied to polyester as disperse dyes and their fastness properties were studied.     

Distribution Studies of Actinides Using a Tetradentate Extractant, 4,4′-Nonanedioyl-Bis(2,4-Dihydro-5-Methyl-2-Phenyl-3H-Pyrazol-3-One)

Abstract

The extraction of Th(IV), UO₂(II), Am(III), and Eu(III) from aqueous acid by a tetradentate extractant, 4,4′-nonanedioyl-bis(2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one), H₂NDBP, has been studied and compared with two bidentate model compounds, 4-hexanoyl-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one, HHMPP, and 4-benzoyl-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-one, HBMPP. The distribution coefficients of UO₂(II), Am(III), and Eu(III) were somewhat larger using H₂NDBP relative to the model compounds under the conditions studied. However, the Th(IV) extraction using H₂NDBP was greatly enhanced when compared to HBMPP or HHMPP. The distribution coefficient for Th(IV) from 0.5 M HNO₃ was 11.6 using 3.0 × 10^?3 M H₂NDBP compared with values of D < 0.01 using 3.0 × 10^?3 M HBMPP or HHMPP.     

Inhibition of mild steel corrosion in hydrochloric acid solution by triazole derivatives: Part I. Polarization and EIS studies

A comparative study of 5-amino-1,2,4-triazole (5-ATA), 5-amino-3-mercapto-1,2,4-triazole (5-AMT), 5-amino-3-methylthio-1,2,4-triazole (5-AMeTT) and 1-amino-3-methylthio-1,2,4-triazole (1-AMeTT) as inhibitors for mild steel corrosion in 0.1 M HCl solution at 20 °C was carried out. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques were applied to study the metal corrosion behaviour in the absence and presence of different concentrations of these inhibitors under the influence of various experimental conditions. Measurements of open circuit potential (OCP) as a function of time till reaching the steady-state potentials (E_st) were also established. The studies have shown that 5-AMT was the most efficient inhibitor reaching values of inhibition efficiency (IE%) up to 96% at a concentration of 10⁻³ M. Polarization curves showed that the four studied compounds act as mixed inhibitors. The potential of zero charge (PZC) of mild steel was determined in 0.1 M HCl in the absence and presence of the studied inhibitors. The effect of chemical structure of the four tested inhibitors was discussed. Results obtained from OCP versus time, polarization and impedance measurements are in good agreement.     

Reactions of hydrazonoyl halides 44 [1]: synthesis of some new 1,3,4-thiadiazolines, 1,3,4-selenadiazolines and triazolino[4,3- a ]pyrimidines

1,3,4-Thiadiazolines, 1,3,4-selenadiazolines and triazolino[4,3-a]pyrimidines have been synthesized from 3-aza-[2,4-dimethyl(1,3-thiazol-5-yl)-2-bromo-3-substituted-amino]prop-2-en-1-ones with potassium thiocyanate, potassium selenocyanate, alkyl carbodithioates and 6-methyl-2-methylthio-4-substituted 3,4-dihydropyrimidine-5-carboxylates. Structures of the newly synthesized compounds have been established by elemental analysis, spectral data and alternative synthesis whenever possible. Some of products have been tested towards bacteria.     

1-(5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-基)-3-(吡啶-3-基甲基)脲的合成

以5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酸与二氯亚砜为起始原料,经酰氯化反应、酰胺反应、霍夫曼重排以及水解反应生成中间体5-(4-氯苯基)-1-(2,4-二氯苯基)-3-氨基-4-甲基-1H-吡唑,再经过与氯甲酸苯酯反应、胺酯交换反应得到标题化合物,其结构经1HNMR、MS谱确证,总收率26.9%。     

Untersuchungen zur regioselektiven Halogenierung von 4-Amino-2-iodmethyl-6-methyl-pyrimidinen

Studies on the Regioselective Halogenation of 4-Amino-2-iodomethyl-6-methylpyrimidines In the presence of oxidants, 4-amino-2-iodomethyl-6-methylpyrimidines 2 undergo regioselective reactions in the positions 2 and/or 5. Thus, the reaction of 2a with hydrogen peroxide proceeds under dealkylation and iodination to give 4-amino-5-iodo-6-methylpyrimidine 7 . Depending on reaction temperature and molar ratios the reaction of 2a with bromine or chlorine leads to the corresponding 4-amino-5-halogeno-2-halogenomethyl-6-methyl-pyrimidines 2c, 9a and 9d . The 5-substituted pyrimidines 2b, c afford the 2-bromo (or chloro) methyl derivatives 9b, c .     

Synthesis of polyazaheterocycles by Michael addition of CH acids to α,β-unsaturated nitriles. Synthesis of pyrido[1,2-a]benzimidazole and pyrimido[5′,4′: 5,6]pyrido[1,2-a]benzimidazole derivatives

Addition of 1H-benzimidazole-2-carbonitrile ( 1 ) to arylidenemalononitrile ( 2 ) gave 1-amino-3-aryl pyrido[1,2-a]benzimidazole-2,4-dicarbonitrile ( 3 ), 2-aryl-benzimidazole ( 4 ) and 1H-benzimidazole-2-acetonitrile,α-(arylmethylene) ( 5 ). Compounds ( 3 ) reacted with formamide yielding 4-amino-5-aryl pyrimido[5′,4′: 5,6]pyrido[1,2-a]benzimidazole ( 6 ).