Cyclopropanation of methyl (2<Emphasis Type="Italic">E</Emphasis>)-3-[(1<Emphasis Type="Italic">R</Emphasis>,6<Emphasis Type="Italic">S</Emphasis>)-7,7-dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-en-4-yl]prop-2-enoate with dichlorocarbene and diazomethane

Cyclopropanation of methyl (2E)-3-[(1R,6S)-7,7-dimethyl-2-oxo-3-oxabicyclo[4.1.0]hept-4-en-4-yl]prop-2-enoate with dichlorocarbene occurred at the endocyclic double bond, while its reaction with diazomethane in the presence of Pd(acac)₂ involved the exocyclic double bond. The resulting lactones reacted with sodium methoxide in methanol via opening of one cyclopropane fragment.     

AN UNUSUAL ADDITION AND RING-CLOSURE REACTION OF 1-(2-BROMOETHYL)-2,3-DIHYDRO- 3-PROPYL-1,3,2-BENZO-DIAZAPHOSPHORIN-4(1H)-ONE 2-OXIDE WITH CARBON DISULFIDE FOR A NEW AND CONVENIENT SYNTHESIS OF THE FUSED PHOSPHORUS HETEROCYCLIC COMPOUND

ABSTRACT

The reaction of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzodiazaphosphorin-4(1H)-one 2-oxide with carbon disulfide takes an alternative pathway in the use of different bases. The sodium hydride mediated reaction leads to the formation of the tricyclic fused 1,2,3,4,4a,4b,5,6-octahydro-6-oxo-5-propyl-4-thia-3,4b,4a-thiazphosphaphenanthridine 4a-oxide via addition of H-P bond across the double bond of carbon disulfide followed by intramolecular cyclization. In the presence of triethylamine, refluxing a mixture of 1-(2-bromoethyl)-2,3-dihydro-3-propyl-1,3,2-benzodiazaphosphorin-4(1H)-one 2-oxide with carbon disulfide in benzene takes an unusual course with formation in excellent yield of the first example of fused phosphorus heterocyclic 4-[1′-(β-bromoethyl)-4′-oxo- 3′-propyl-1′,2′,3′,4′-tetrahydro-1,3,2-benzodiazaphosphorin-2′- sulfide]-1,2,3,4,4a,4b,5,6-octahydro-6-oxo-5-propyl-3,4b, 4a-thiazphosphaphenanthridine 4a,2′-dioxide, which was confirmed by spectroscopic methods, microanalyses and single crystal X-ray structure determination.     

4-hydroxy-2-quinolones. 202*. Synthesis, chemical and biological properties of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

In continuation of the search for potential analgesics amongst 4-hydroxyquinol-2-one derivatives we have proposed and carried out a preparative method of synthesis of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides. It has been shown that bromination of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid allylamide using an equivalent of molecular bromine occurs with a conventional addition of the halogen to the allyl double bond and not with halocyclization. The results of the study of the analgesic properties of the compounds prepared are presented.     

The preparation of ethyl 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-4-oxo-1,8-naphthyridine-3-carboxylate

Ethyl 7-Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid has been prepared by a route involving masking of the C_2,3 double bond through reduction, followed by regioselective deprotonation of the C₅ position and methylation and then regeneration of the C_2,3 double bond via selenation, oxidation, and syn-elimination.     

茶螺烷酮合成的新工艺

以α-紫罗兰酮为原料,经间氯过氧苯甲酸环氧化、甲醇钠开环、超声波辐射Pd/C催化甲酸铵选择性碳碳双键加H、硼氢化钠还原、脱水环化及乙酰丙酮亚钴催化烯丙位氧气氧化等6步反应,以总收率52.6％合成了食用香料2,6,10,10-四甲基-1-氧杂-螺[4.5]-6-癸烯-8-酮(茶螺烷酮)。 用IR、1H NMR、MS谱及元素分析等测试技术表征了产物的结构和组成。     

Tin-free Giese reaction and the related radical carbonylation using alkyl iodides and cyanoborohydrides

Tin-free Giese reaction and the related radical carbonylation process proceeded efficiently in the presence of sodium cyanoborohydride and tetrabutylammonium cyanoborohydride. The reaction took place chemoselectively at the carbon-iodine bond but not at the carbon-bromine and carbon-chlorine bonds. The iodine atom transfer followed by hydride reduction of the resulting carbon-iodine bond is proposed as a possible mechanism.     

Synthese von Pyrimido[1,2-a]benzimidazolen durch Umsetzung von 2-Aminobenzimidazol mit Acetylendicarbonsäure-dimethylester und ihre Überführung in Imidazo[1,2-a]benzimidazole

The main product of the reaction between 2-aminobenzimidazole and dimethyl acetylenedicarboxylate is shown to be methyl 1, 2-dihydro-2-oxo-pyrimido[1, 2-a]benzimidazole-4-carboxylate ( 6 ), which can be methylated at position 1 to give 7 . Catalytic hydrogenation of 7 leads to the 1,2,3,4-tetrahydro derivative 8 , whereas NaBH₄ reduces the ester and, to some extent, the double bond to yield a mixture of 9 and 10 . When a 1-substituted 1, 2-dihydro-4-hydroxymethyl-pyrimido[1, 2-a]benzimidazol-2-one (for example 11 ) is catalytically hydrogenated, the double bond is unaffected, but hydrogenolysis of the alcohol group occurs instead to give 13 . The lactam group is less stable in the tetrahydro series than in the dihydro compounds. For example, the lactam is cleaved when 8 is treated with amines containing a small amount of water, and the monoamides 16 and 17 are formed. Similarly, sodium hydroxyde cleaves the lactam under mild conditions to the dicarboxylic acid 19 , which can be converted to 2, 3-dihydro-1-methyl-2-oxo [1H]imidazo[1, 2-a]benzimidazole-3-acetic acid (4-methyl)piperazide ( 20 ) with thionyl chloride and N-methylpiperazine. However, when 7 is treated with methylamine at low temperature, the amide 22 is formed, whilst at room temperature the amine attacks both the ester and the double bond to give 23 . The structure of 8 was confirmed by X-ray analysis.     

A general method for the preparation of 2-substituted-4-oxo-3-quinolinecarboxylic acids

A general method for preparing 2-substituted-4-oxo-3-quinolinecarboxylic acids and 2-substituted-4-oxo-1,8-naphthyridine-3-carboxylic acids as new analogs in the quinolone class of antiinfectives has been developed. The reaction of a Grignard reagent in the presence of copper(I) iodide with the 4-oxo-3-quinolinecar-boxylic acid esters and 4-oxo-1,8-naphthyridine-3-carboxylic acid esters yields the desired 2-substituent. Re-introduction of the 2,3-double bond is effected by phenylselenation of the 3-position, oxidation to the selen-oxide, and in situ syn-elimisation. Depending on the degree of steric crowding between the 2-substituent and the 3-carboxylic acid group, hydrolysis of the ester to the carboxylic acid could be carried out under acidic or basic conditions.     

Furan derivatives. Part 9. Synthesis and properties of cyclohepta[cd]benzofurans

Cyclohepta[cd]benzofurans 1a-c were synthesized by heating (5-oxo-5H-benzocyclohepten-4-yloxy)acetic acids 7a-c with sodium acetate in acetic anhydride or by irradiation of 7a-c in acetonitrile. Several reactions such as protonation, catalytic hydrogenation, Diels-Alder reaction, acylation, and photoreaction were examined for 1a-b . The results show that cyclohepta[cd]benzofurans have both properties of heptafulvene and benzofuran. The carbon-carbon double bond in the furan ring of 1a has aromatic character, however, the carbon-carbon double bonds in the seven-membered ring have olefinic character.     

Hydrogenation of the Sodium Salt of 2-Oxo-4-(3-pyridyl)butenoic Acid on Palladium Black

We have studied the hydrogenation of the sodium salt of 2-oxo-4-(3-pyridyl)butenoic acid on palladium black in the temperature range 20-70°C in aqueous-alcohol medium. The products of the reaction are the sodium salts of 2-oxo-4-(3-pyridyl)butanoic acid and 2-hydroxy-4-(3-pyridyl)butanoic acid together with hydrogenolysis products. The reaction occurs via a series-parallel mechanism.     

Synthesis and Complexing Properties of Alkyl (3-Oxo-2,3-dihydrothiophen-2-ylidene)- and (4-Oxothiazolidin-5-ylidene)acetate Derivatives

Condensation of dimethyl and diethyl acetylenedicarboxylate with thioacetamides gave the corresponding alkyl (3-oxo-2,3-dihydrothiophen-2-ylidene)- and (4-oxothiazolidin-5-ylidene)acetates. Treatment of these compounds with zinc in acetic acid resulted in reduction of the exocyclic double bonds. The products can be used in membrane processes as sodium cation carriers.     

Synthesis of some substituted 1,3-thiazolines and 1,3-thiazolidines

Sodium salts of 2, 2-dimethyl-4-mercapto-5-oxo-1,3-thiazoline and 2-oxo-3-mercapto-1-thia-4-azaspiro[4.5]dec-3-ene, obtained from a solvate of sodium cyanodithioformate with three molecules of dimethylformamide, acetone, or cyclohexanone in the presence of morpholine, react with chlorothioformic dimethylamide with the formation of 2,2-dimethyl-5-oxo-4-(dimethylaminothiocarbonylthio)-1,3-thiazoline and 2-oxo-3-(dimethylaminothiocarbonylthio)-1-thia-4-azaspiro[4.5]dec-3-ene, respectively, and during acidolysis by hydrochloric acid they are converted to 2,2-dimethyl-5-oxo-4-thiono-1,3-thiazolidine and 2-oxo-3-thiono-1-thia-4-azaspiro[4.5]decane. The latter compounds are facilely phosphorylated by dialkyl chlorophosphonates at the nitrogen atom. The reaction of the solvate of sodium cyanodithioformate with three molecules of dimethylformamide with chloroacetone in the presence of morpho-line occurs anomalously with the formation of cyanothioformic morpholide.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2590–2593, November, 1990.     

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.     

New and efficient routes for the synthesis of murrayaquinone A and murrayanine

Three new routes were established for the synthesis of biologically active murrayaquinone A and a new method was developed for synthesis of murrayanine from the same starting material as 4-hydroxy carbazole. During the synthetic course a few novel observation were recorded, which include two one pot reaction sequences and C–N bond cleavage by sodium cyanoborohydride.     

Oxazoline N-oxide mediated [2 + 3] cycloadditions. Application to a formal synthesis of (+)-carpetimycin A

[formula: see text] Cycloaddition between gamma,delta-unsaturated beta-enamino ester 9 and camphor-derived oxazoline N-oxide 8 afforded a single adduct, 14. Dipolarophile 9 proved to be very reactive despite the substitution on the double bond. Stereoselective sodium cyanoborohydride reduction of the imminium intermediate 14a gave rise stereoselectively to beta-amino ester derivative 15a. Oxidative acidic hydrolysis, oxidation of the resulting aldehyde 18, deprotection, and cyclization afforded the beta-lactam 23, a direct precursor of (+)-carpetimycin A.     

Preparation of enantiomerically pure (R)- and (S)-3-amino-3-phenyl-1-propanol via resolution with immobilized penicillin G acylase

Ethyl 2,4-dioxo-4-phenylbutyrate, obtained by condensation of acetophenone with diethyl oxalate, was converted to 3-oxo-3-phenyl-1-propanol in 90% yield by reaction with baker’s yeast. Reductive amination with sodium cyanoborohydride in the presence of ammonium acetate gave the racemic 3-amino-3-phenyl-1-propanol in 65% yield. Enzymatic resolution of the corresponding N-phenylacetyl derivative with penicillin G acylase, immobilized on an epoxy resin gave (S)-amide and (R)-amino alcohol in high enantiomeric purity (ee >99%) and >45% yields for each enantiomer.     

Cyclodimerization of the Stevens Rearrangement Products from 4-Alkoxy-2-butynyl(alkoxycarbonylmethyl)dimethyl-ammonium Salts into Cyclohexene Derivatives

4-Alkoxy-2-butynyl(alkoxycarbonyl)dimethylammonium salts undergo 3,2-Stevens rearrangement by the action of the corresponding sodium alkoxides. Hydrolysis of the rearrangement products with dilute hydrochloric acid gives 3-alkoxy-2-oxo-3-pentenoic acid esters which are converted into 3-methylene-2-oxo-4-pentenoates via 1,4-elimination of alcohol. [2 + 4]-Cyclodimerization of 3-methylene-2-oxo-4-pentenoates leads to 1,4-bis(alkoxalyl)-4-vinylcyclohexenes.     

Synthesis of 2-chloro-2-imidoylaziridines via aza-Darzens-type reaction of 3,3-dichloro-1-azaallylic anions and N-(arylsulfonyl)imines

3,3-Dichloro-1-azaallylic anions, generated by deprotonation of alpha,alpha-dichloroketimines 10 with lithium diisopropylamide, reacted with N-sulfonylaldimines 7 to produce the Mannich-type products N-[2,2-dichloro-3-(N-alkylimino)-1,3-diarylpropyl]benzenesulfonamides 11. The latter stable compounds were hydrolyzed at the imino functionality to afford N-[2,2-dichloro-3-oxo-1,3-diarylpropyl]benzenesulfonamides 12 in excellent yields. N-[2,2-Dichloro-3-(N-alkylimino)-1,3-diarylpropyl]benzenesulfonamides 11 were cyclized to cis-3-aryl-2-chloro-2-imidoylaziridines 19 in 81-99% yield with high diastereoselectivity, representing a novel and readily available class of stable 2-chloroaziridines. Finally, a highly stereoselective entry to 2-(aminomethyl)-2-chloroaziridines 27 (70-98% yield; de > 95-99) was worked out from the reaction of cis-3-aryl-2-chloro-2-imidoylaziridines 19 and sodium cyanoborohydride in the presence of acetic acid. The latter 2-(aminomethyl)aziridines 27 represent stereochemically defined small azaheterocyclic rings which were scarcely reported in the literature.     

Synthesis of amino derivatives of triazolopyrimidine

Heterocyclization of 1-(4,6-dimethylpyrimidin-2-yl)-4-R-thiosemicarbazides by the action of methyl iodide in ethanol in the presence of sodium acetate is accompanied by Dimroth rearrangement leading to the formation of 5,7-dimethyl-2-R-amino[1,2,4]triazolo[1,5-a]pyrimidines. Analogous heterocyclization of 4-aryl-1-(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)thiosemicarbazides gives 3-arylamino-7-methyl-5-oxo-[1,2,4]triazolo[4,3-a]pyrimidines. The presence in the pyrimidine ring of a carbonyl group capable of forming hydrogen bond with protons of the amino group stabilizes the molecule, thus hampering the Dimroth rearrangement.     

Michael Addition of 3-Oxo-3-phenylpropanenitrile to Linear Conjugated Enynones: Approach to Polyfunctional δ-Diketones as Precursors for Heterocycle Synthesis

Reaction of linear conjugated enynones, 1,5-diarylpent-2-en-4-yn-1-ones [Ar¹C≡CCH=CHC(=O)Ar²], with 3-oxo-3-phenylpropanenitrile (NCCH₂COPh) in the presence of sodium methoxide MeONa as a base in MeOH at room temperature for 4–26 h affords polyfunctional δ-diketones as a product of regioselective Michael addition to the double carbon–carbon bond of starting enynones. The δ-diketones have been formed as mixtures of two diastereomers in a ratio of 2.5:1 in good general yields of 53–98%. A synthetic potential of the obtained δ-diketones has been demonstrated by heterocyclization with hydrazine into substututed 5,6-dihydro-4H-1,2-diazepine.