Reactions of 4-chloroacetoacetic esters with thioureas

Several heterocyclic acetic acids and esters were synthesized by allowing the appropriate thiourea, ethylenethiourea or trimethylenethiourea to react with 4-chloroacetoacetic esters, followed by acid hydrolysis to the hydrochlorides of the free acids. Both esters and acids of 2-aminothiazole-4-acetic acid, 5,6-dihydro-imidazo[2,1-b]thiazole-3-acetic acid and 6,7-dihydro-5H-thiazolo[3,2-c]pyrimidine-3-acetic acid were obtained.     

Ethyl 2-nitroacetoacetate as a new synthetic equivalent of ethoxycarbonylnitrile oxide

It was shown that ethyl 2-nitroacetoacetate is a synthetic precursor of ethoxycarbonylnitrile oxide as well as of isoxazole- and isoxazoline-3-carboxylic acids and their esters. The elimination of acetic acid from ethyl 2-nitroacetoacetate occurs in a mixture of acetic acid and acetic anhydride in the presence of strong mineral acids,e.g., H₂SO₄, at room temperature and gives isoxazolines in yields of up to 85–91 %.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 103–105, January, 1994.     

A Novel Synthesis of 4‐Pyridazineacetic Acids via Ring Expansion of N‐Cyanomethylated 3‐Pyrazoline‐4‐acetic Acids

A novel synthetic route to 4‐pyridazineacetic acids 10 – 12 has been achieved by the ring‐expansion reaction of N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 – 9 . 1H‐Pyrazole‐4‐acetic acids 1 – 3 were reacted with iodoacetonitrile in the presence of triethylamine in refluxing acetonitrile to give the corresponding C‐cyanomethylated 1H‐pyrazole‐4‐acetic acids 4 – 6 as major products together with N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 8 as minor products. On the other hand, reactions of 1 and 3 with chloroacetonitrile in the presence of triethylamine in refluxing chloroform afforded the corresponding N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 9 as major products. Thermal treatment of 7 – 9 with sodium hydride in N,N‐dimethylformamide caused ring expansion to yield the corresponding 4‐pyridazineacetic acids 10 – 12 .     

Synthesis of 5-aryl-2-oxazolepropionic acids and analogs. Antiinflammatory agents

Condensation of 2-bromoacetophenones with sodium succinimide gave N-phenacylsuccinimides ( 1 ) which were opened with sodium hydroxide to N-phenacylsuccinamic acids ( 2 ). The latter were cyclized to 5-aryl-2-oxazolepropionic acids ( 3 ) in sulfuric acid. Similar cyclization of N-phenacylphthalamic acid ( 5 ) and succinic acid 2-benzoylhydrazide ( 7 ) gave o-(5-phenyl-2-oxazolyl)benzoic acid ( 6 ) and 5-phenyl-1,3,4-oxadiazole-2-propionic acid ( 8 ). The succinamic acids 2 and the phthalamic acid 5 were observed to recyclize to the corresponding imides ( 1 and 4 ) on heating, and the succinic acid hydrazide 7 was similarly cyclized to N-benzamidosuccinimide ( 9 ) with acetic anhydride. Antiinflammatory screening data are reported for 3 , 6 and 8 .     

Studies on quinoline derivatives and related compounds. 1. A new synthesis of 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids

A novel preparative method for 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids was developed. The key process is the cyclization of N-alkylanilinomethylenemalonales, which was effected successfully in the presence of polyphosphoric acid, polyphosphate ester, boron tri-fluoride or a mixture of acetic anhydride and sulfuric acid. With phosphorus oxychloride, N-alkylanilinomethylenemalonates yielded 1-alkyl-4-chloro-3-carbethoxyquinolinium salts which were hydrolyzed readily to ethyl 1-alkyl-1,4-dihydro-4-oxo-3-quinolineearboxylates or their acids. By means of this novel method several new 1-alkyl-1,4-dihydro-4-oxo-3-quinolineearboxylic acids were prepared.     

N-(2,2,2-Trichloroethylidene)- and N-(1-Hydroxy-2,2,2-trichloroethyl)amides in C-Amidoalkylation Reaction of Functionally-substituted Aromatic Compounds

A reaction with phenol and pyrocatechol of N-(2,2,2-trichloroethylidene)arenesulfonyl-, ethoxycarbonylamides and 1-hydroxy-substituted N-(2,2,2-trichloroethyl)amides of arenesulfonic, carbamic, and acetic acids in the presence of oleum or in sulfuric acid provided the corresponding (1-amido-2,2,2-trichloroethyl)-substituted phenols. N-(2,2,2-Trichloroethylidene)-4-chlorobenzenesulfonamide reacted with salicylamide in the presence of oleum to afford 3-aminocarbonyl-4-[2,2,2-trichloro-1-(4-chlorobenzenesulfonamido)ethyl]benzene whereas the 1-hydroxy-2,2,2-trichloroethylamides of the acetic, carbamic, and arenesulfonic acids did not enter into such reactions.     

Die umsetzung von azlactonen mit CH-aciden verbindungen. 2. Mitteil

Alkyl cyanoacetate, malonate, acetoacetate and methylsulfonyl acetic acid ethyl ester are acylated by alkylidenazlactones. The acyl compounds easily form alkylideneteramic acids by condensations. The acylcyanoacetates 2 isomerize into aminopyrrolinones 3 via acid catalysis.     

Synthesis and exchange reactions of 5-alkyl-2-oxo-6-thioxo-1,2,3,6-hexahydropyrimidine-4-carboxylic acids

An improved preparation of 2-oxo-6-thioxo-1,2,3,6-hexahydropyrimidine-4-carboxylic acid 3, a potent inhibitor of dihydroorotase is presented. Trans-5-alkyl-2-oxo-6-thioxohexahydropyrimidine-4-carboxylic acids 12a-c were synthesised via the thiation of the p-methoxybenzyl esters of 5-alkyldihydroorotic acids with Lawesson's reagent followed by subsequent de-protection. The corresponding cisisomers were prepared by reduction of 5-alkyl-6-thioxoorotic acids with zinc in acetic acid. The stability and exchange reactions of 12a-c under physiological conditions were investigated by ultra-violet and ¹H nmr spectroscopy. The attempted synthesis of 16 , a fused cyclopentyl derivative of 3 is also presented.     

Reaction of 2-(phenylamino)benzoic and 2-(phenylamino)- and 2-methyl-6-phenylpyridine-3-carboxylic acid hydrazides with succininc anhydride

Reactions of 2-(phenylamino)benzoic and 2-(phenylamino)- and 2-methyl-6-phenylpyridine-3-carboxylic acid hydrazides with succinic anhydride in organic solvents at room temperature gave the corresponding 4-(2-aroylhydrazinyl)-4-oxobutanoic acids. The reactions in boiling acetic acid afforded N-(2,5-dioxopyrrolidin-1-yl)benzamide or N-(2,5-dioxopyrrolidin-1-yl)pyridine-3-carboxamide.     

Keggin-type mono lacunary silicotungstate supported onto zirconia: synthesis,characterization, and esterification reaction

A solid acid catalyst comprising of lacunary silicotungstate and zirconia was synthesized and characterized by physicochemical techniques. Surface morphologies of support and catalyst were studied by scanning electron microscopy. Catalytic properties were evaluated for the esterification of n-butanol with acetic acid. Esterifications of sec-butanol and isobutanol with acetic acid as well as the esterification of n-butanol with different acids such as formic acid and propionic acid were carried out under optimized conditions. Catalytic activities for calcined as well as recycled catalysts were also evaluated for the esterification under optimized condition.     

Aromatization of aliphatic compounds—II: On the aromatization of some alkyl substituted cyclohexenones

2,3,5-Trimethyl-4-oxo-cyclohex-2-en acetic acid 5 treated with PyHCl aromatizes to the corresponding 2,3,5-trimethyl-benzene acetic acid 9 through a mechanism different from that leading to arylacetic acids from 2-oxo-cyclohex-3-en acetic acids 3. 2,3,4,6-Tetrakyl cyclohexenone 11, lacking the 2-carboxymethyl group, also aromatizes to tetralkyl benzene 13.     

1,2- and 1,4-Diacetoxylation of 1,3-butadiene via 2,5-dihydrothiophene 1,1-dioxide as a probable intermediate

Sulphur dioxide has been found to promote a novel liquid-phase oxidation of 1,3-butadiene in acetic anhydride with oxygen gas and catalytic amounts of concentrated protic acids (e.g. hydrobromic acid). 1,2-Diacetoxy-3-butene and 1,4-diacetoxy-2-butene together with small amounts of 1-hydroxy-2-acetoxy-3-butene and 1-hydroxy-4-acetoxy-2-butene are formed in the reaction.     

A convenient synthesis of (2-styrylchromon-8-yl)acetic acids

(2-Styrylchromon-8-yl)acetic acids, structural analogs of (flavon-8-yl)acetic acid (FAA) have been synthesized with satisfactory yields according to two different methods. The ¹H and ¹³C nmr data fovor the S-trans stereoisomers.     

Synthesis of E- and Z-o-Methoxy-Substituted 2,3-Diphenyl Propenoic Acids and Its Methyl Esters

A series of stereoisomeric o-methoxy-substituted 2,3-diphenyl propenoic acids and their methyl esters have been synthesized. The E isomers were prepared by a modified Perkin condensation (substituted benzaldehyde, phenylacetic acid, Et₃N/acetic anhydride). The difficult to access Z isomers were obtained conveniently in good yields when the appropriate coumarin derivatives were allowed to react with KOH and CH₃I in DMSO.     

Efficient Synthesis of Functionalized 2H-Thiopyrans via Hetero-Diels-Alder Reactions of an Enaminothione with Electrophilic Olefins

Summary.  The hetero-Diels-Alder reaction of 3-dimethylamino-1-(2-thienyl)-2-propene-1-thione (diene) with substituted β-nitrostyrenes, as well as maleic and fumaric acids (dienophiles) yielded 3,4-dihydro-2H-thiopyran derivatives. The treatment of some of those cycloadducts with acetic acid caused elimination of dimethylamine, affording stable 2H-thiopyrans. A reaction of the diene with maleic anhydride furnished a cycloadduct which underwent spontaneous rearrangement to form an N,N-dimethylamide derivative. Cycloadditions of the diene to maleimide, N-phenylmaleimide, maleic acid monoanilide, diethyl maleate, fumarate, and butenolide carried out in the presence of acetic anhydride were followed by elimination of dimethylamine under formation of stable 2H-thiopyran derivatives. Received February 19, 2001. Accepted (revised) March 12, 2001     

Gymnemasäure,das antisaccharine Prinzip von Gymnema sylvestre R. Br. Isolierungen und Identifizierungen Glykoside und Aglykone 288. Mitteilung

The isolation, characterisation, purity control and probable structure of gymnemic acid, the antisaccharine principle of Gymnema sylvestre R. Br. (Asclepiadaceae) has been reported. According to the results, gymnemic acid is the D-glucuronide of a probably new hexahydroxy-δ¹²-oleanene which has been named gymnemagenin and which is esterified with various combinations of the following five acids: formic, acetic, n-butyric, isovaleric, and tiglic acid. Gymnemic acid is not an absolutely pure substance. It is composed predominantly of gymnemic acid A₁, which is accompanied by components having similar properties, especially the gymnemic acids A₂, A₃ and A₄. The difference between these components probably lies in the absence or presence of one of the five named acids.     

Synthesis of thiadiazoles,triazoles and oxadiazoles from sulfonyl acetic acids via a common route

A new class of five membered heterocycles, thiadiazoles, triazoles and oxadiazoles were prepared from sulfonyl acetic acids via acid hydrazides.     

Occupational exposure to low levels of organic and inorganic substances in a chemical plant for the production of terephtalic acid dimethyl ester

The aim of our study was the evaluation of personal exposure to chemical pollutants in workers employed in a plant for the production of terephtalic acid dimethyl ester. Chemical agents have been included in the monitoring program on the basis of the industrial process. In the plant, the oxidation of p-xylene is performed by air and the resulting acid is esterified with methyl alcohol. Purified terephtalic acid dimethyl ester is then utilized for the production of polyethylene terephtalate. The environmental monitoring included terephtalic acid dimethyl ester, p-toluic acid methyl ester, terephtalic acid, p-xylene, methylacetate, methylbenzoate, formic acid, acetic acid, methanol, and the catalysts cobalt acetate and manganese (II) acetate tetrahydrate. Personal exposure to the cited airborne substances was performed in the breathing zone of six workers. Air samplings were carried out by drawing air through glass fibre filters (terephtalic acid dimethyl ester, p-toluic acid methyl ester and terephtalic acid aerosols), by active adsorption (methanol, formic and acetic acids vapours). p-Xylene, methylacetate and methylbenzoate vapours were collected by passive sampling. Cellulose nitrate filters were used for cobalt and manganese salts samplings. Analyses were performed by UV detection high-performance liquid chromatography (terephtalic acid dimethyl ester, p-toluic acid methyl ester and terephtalic acid), flame ionization detection gas chromatography (p-xylene, acetic acid methyl ester and benzoic acid methyl ester), ion chromatography (formic and acetic acids) and inductively coupled plasma-mass spectrometry (cobalt and manganese). The results were evaluated according to the threshold limit values (TLVs) of the American Conference of Governmental Industrial Hygienists (ACGIH) and indicated that the environmental levels of the workplace pollutants were well below the threshold limit values-time weighed average (TLV-TWA) adopted by the American Conference of Governmental Industrial Hygienists for 2002, although for three substances the TLVs were not available.     

Synthesis of thienothiazocinoisoindolediones and thienothiazinoisoindolones from mercaptothiophenes and chloromethylphthalimide

2-Thienylthiomethylphthalimides 3a,b were synthesized by action of Chloromethylphthalimide on 2-or 3-mercaptothiophene. Reduction of 3a,b and Wittig reaction using carbethoxycarbonyltriphenyl-phosphorane gave the corresponding acetic acids 5a,b which cyclized under Friedel and Crafts conditions to lead the thienothiazocinoisoindolediones 6a,b. Thienothiazinoisoindolones 7a,b were obtained from hydroxyisoindolones derivatives 4a,b in acid conditions via an acyliminium ion.     

Excess molar volumes of carboxylic acid mixtures: binary mixtures of formic,acetic, propionic,n-pentanoic and iso-pentanoic acids at 298.15 K

Systematic measurements of density were performed in six binary mixtures of carboxylic acids. Derived from the densities the excess molar volumes V^E are always positive, with the exception of the formic acid+acetic acid system where V^E is negative for x<0.75 and positive for mixtures rich in formic acid. The extremal values of V^E are about −0.06 and +0.02 cm² mol⁻¹. As a rule, the excess molar volume curves are slightly asymmetrical with respect to composition having the maximal values of about 0.15 cm³ mol⁻¹ in the formic acid+propionic acid system; 0.10 cm³ mol⁻¹ in the acetic acid+ propionic acid system; 0.35 cm³ mol⁻¹ in the acetic acid+n-pentanoic acid system; 0.65 and 0.62 cm³ mol⁻¹ in the systems of n-pentanoic and iso-pentanoic acids with formic acid. A qualitative interpretation of the presented results is given taking into account almost complete dimerization of carboxylic acids and the formation of mixed dimers of these acids.