Synthesis and Properties of 2-Alkyl-1-(2-aminoethyl)pyrroles

3-Chloropropenyl alkyl ketones or 2-methoxy-3-chloropropyl alkyl ketones in reaction withethylenediamine furnish previously unknown 2-alkyl-1-(2-aminoethyl) pyrroles. Their reaction with 2'2'-dichlorodiethyl ether gave rise to 2-alkyl-1-(2-morpholinoethyl)pyrroles, with anhydrides ofdicarboxylic acids the corresponding amidoacids and imides of dicarboxylic acids were obtained.     

Facile synthesis of 6-organyl-4-(trifluoromethyl)pyridin-2(1H)-ones and their polyfluoroalkyl-containing analogs

The three-component cyclization of 3-polyfluoroalkyl-3-oxopropanoates and methyl ketones with ammonium acetate affords 6-organyl-4-(polyfluoroalkyl)pyridin-2(1H)-ones (organyl is alkyl, aryl, or hetaryl). The synthesized pyridones were evaluated for antifungal, antibacterial, and analgesic activity.

     

Synthesis and Structure of Disodium 1,2-Bis(2-oxocycloalkylidene)ethane-1,2-diolates and Disodium 4-Alkoxy-4-oxo-1-(2-oxocycloalkylidene)but-2-ene-1,2-diolates

Russian Journal of General Chemistry - Two-stage condensation of cycloalkyl ketones with dimethyl oxalate or alkyl acetates with dialkyl oxalates and cycloalkyl ketones produced disodium...     

A highly diastereoselective synthesis of (E)-B-2-(1-cyclopropyl-1-alkenyl)-1,3,2-dioxaborinanes. Isolation and oxidation to alkyl cyclopropyl ketones

A convenient, novel synthesis of alkyl cyclopropyl ketones based on Z-1-bromo-1-alkenylboronate esters is developed. α-Bromo-(Z)-1-alkenylboronate esters readily available from literature procedures smoothly undergo a reaction with cyclopropylmagnesium bromide in tetrahydrofuran to provide the corresponding ‘ate’ complexes. These ‘ate’ complexes undergo intramolecular nucleophilic substitution reactions to provide the corresponding (E)-1-alkenylboronate esters containing cylcopropyl moiety for the first time in good isolated yields (68-82%). The carbon skeleton present in these intermediates is confirmed by oxidation with hydrogen peroxide and sodium acetate to afford the corresponding alkyl cyclopropyl ketones in good yields (72-85%).     

Conversion of 2-(O-hydroxyphenyl) alkyl ketones into 2-hydroxymethylchroman derivatives

2-Hydroxymethylchromans are the only products arising from the oxidation by m-chloro-perbenzoic acid of the β-(o-hydroxyphenyl) olefins VI, obtained in turn form 2-(o-hydroxy-phenyl) alkyl ketones (I) by the Wittig olefination with triphenylphosphonium methylide.     

Convenient synthesis of 3-methyl-1-(4-pyridinyl)-2-butanone using phenyllithium as a metalating agent

3-Methyl-1-(4-pyridinyl)-2-butanone has been synthesized via a short and convenient method based upon acylation of 4-picoline by phenyllithium followed by reaction with ethyl isobutyrate. This procedure can be extended to the preparation of various alkyl pyridyl ketones, intermediates in the synthesis of potential anti-tumor 6-substituted 7H-pyridocarbazole dimers.     

Haloacetylated enol ethers. 13. Synthesis of N-[1-aryl(alkyl)-3-oxo-4,4,4-trichloro-1-buten-1-yl]-o-phenylenediamines and 2-trichloromethyl-4-aryl-3H-1,5-benzodiazepines

The synthesis and isolation of the intermediates N-[1-aryl(alkyl)-3-oxo-4,4,4-trichloro-1-buten-1-yl]-o-phenylenediamines 2a-f and the corresponding 2-trichloromethyl-4-aryl-3H-1,5-benzodiazepines 3c-g or benzimidazoles 4a-b derivatives obtained from the intramolecular cyclization of 2a-f or from direct cyclo-condensation reaction of β-alkoxyvinyl trichloromethyl ketones 1a-g with o-phenylenediamine, is reported. Depending of the structure of the β-alkoxyvinyl trichloromethyl ketones or the N-[1-aryl(alkyl)-3-oxo-4,4,4-trichloro-buten-1-yl]-o-phenylenediamines and the reactions conditions, benzimidazoles or 3H-1,5-benzodiazepines were obtained.     

Synthesis of benzothiophene derivatives by Pd-catalyzed or radical-promoted heterocyclodehydration of 1-(2-mercaptophenyl)-2-yn-1-ols

Novel and convenient approaches to benzothiophene derivatives 3 and 5 have been developed, based on heterocyclization reactions of 1-(2-mercaptophenyl)-2-yn-1-ols 2 or 4, respectively, readily available from alkynylation of 2-mercaptobenzaldehydes or 1-(2-mercaptophenyl) ketones 1. In particular, 1-(2-mercaptophenyl)-2-yn-1-ols 2, bearing a CH(2)R substituent on the triple bond (R = alkyl, aryl), were conveniently converted in fair to good yields (55-82%) into (E)-2-(1-alkenyl)benzothiophenes 3 when allowed to react in the presence of catalytic amounts (2 mol %) of PdI(2) in conjunction with KI (KI:PdI(2) molar ratio =10) at 80-100 °C in MeCN as the solvent, through a heterocyclodehydration process. On the other hand, 2-alkoxymethylbenzothiophenes 5 were selectively obtained in fair to excellent yields (49-98%) via a radical-promoted substitutive heterocyclodehydration process, by reacting 1-(2-mercaptophenyl)-2-yn-1-ols 4 (bearing an alkyl or aryl substituent on the triple bond) in alcoholic media at 80-100 °C in the presence of a radical initiator, such as AIBN.     

Convenient Syntheses of Functionalized Dialkyl Ketones and Alkanoylsilanes: 1-(Benzotriazol-1-yl)-1-phenoxyalkanes as Alkanoyl Anion Equivalents

(Benzotriazol-1-yl)-1-phenoxyalkanes 10, prepared by two-step transformations of the corresponding aldehydes, are readily deprotonated at the methine group by BuLi. Subsequent reactions with alkyl halides, aldehydes, ketones, and imines yield the corresponding substituted derivatives that undergo hydrolysis under acidic conditions to afford the expected functionalized ketones 13, 15,17, 19, 21, 24, and25. Two successive lithiations of (benzotriazolyl)phenoxymethane, each followed by reaction with a trialkylsilyl chloride, alkyl halide, aldehyde, or ketone, generate similar intermediates 27, 29, 31,33, and 36. Subsequent hydrolyses of 27, 29, 31, 33, and 36 yield the functionalized ketones 28, 30, and 32 and the alkanoylsilanes 34 and 37 in good yields.     

Synthesis of (2-chlorophenyl)(phenyl)methanones and 2-(2-chlorophenyl)-1-phenylethanones by Friedel-Crafts acylation of 2-chlorobenzoic acids and 2-(2-chlorophenyl)acetic acids using microwave heating

Several 2-(2-chlorophenyl)-1-phenylethanones and (2-chlorophenyl)(phenyl)methanones were prepared by the Friedel-Crafts acylation reaction of 2-(2-chlorophenyl) acetic acids and 2-chlorocarboxylic acids, respectively, in the presence of cyanuric chloride, pyridine, and AlCl₃ or FeCl₃ using microwave heating. The yields of the ketones were significantly higher than those obtained using conventional heating. In addition, similar reactions carried out with the less inexpensive and less toxic FeCl₃ gave titled ketones in comparable yields. Interestingly, the FeCl₃ catalyzed reactions gave pure ketones (no chromatographic purification required), whereas the AlCl₃ catalyzed reaction gave impure product that required chromatographic purification.     

Structure of 2(5)-alkyl-4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones,cyclocondensation products of benzil with aliphatic ketones

The reaction of benzil with methyl alkyl ketones gave three isomeric cyclopentenone derivatives, 2-substituted and cis- and trans-5-substituted 4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones. cis- and trans-2,5-Disubstituted 4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones were formed in analogous reaction of benzil with dialkyl ketones. The structure of the products was confirmed by ¹H NMR spectroscopy and molecularmechanics calculations.     

Synthesis of 2-alkyl-2-(3-cyanopyridin-2-ylthio)propionic acids

Derivatives of 2-alkyl-2-mercaptopropionic acid were synthesized based on the substituted 3-cyanopyridin-2(1H)-thiones. The synthesis was carried out by the heating of a mixture of thione, alkyl methyl ketone, and chloroform in the presence of a base. The reaction proceeds readily for acetone, whereas alkyl methyl ketones require a prolonged heating in the presence of a phase-transfer catalyst. Methyl esters were prepared from the acids obtained. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1967–1970, October, 2007.     

A novel synthesis of 3-(substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)-diones

An improved synthesis of 3-(substituted)pyrimido[4,5-c]pyridazine-5,7(1H,6H)-diones, a known subclass of 4-deazatoxoflavins, is reported. The approach involves treatment of 3-methyl-6-(1-methylhydrazinyl)uracil with representative phenyl and alkyl glyoxal monohydrates, which in turn are obtained by selenium dioxide oxidation of the corresponding phenyl and alkyl methyl ketones. The first entry into 4-monosubstituted isomers is also reported.     

Simplified synthesis of 3-(1-arylsulfonylalkyl) indoles and their reaction with Reformatsky reagents

A simple procedure for the preparation of 3-(1-arylsulfonyl-alkyl) indoles by three-component condensation of indoles, carbonyls, and arenesulfinic acids is presented. The obtained products undergo a Reformatsky reaction leading to alkyl 3-(3-indolyl) alkanoates and (3-indolyl) ketones.     

Synthesis and molecular structure of 1-(pyrimidin-2-yl)-2-(4-aryl-1,3-thiazol-2-yl)hydrazines

Reactions of some 2-hydrazinopyrimidine hydrochlorides with potassium thiocyanate gave 1-(pyrimidin-2-yl)thiosemicarbazides which underwent Hantzsch condensation with aryl chloromethyl ketones to produce 1-(pyrimidin-2-yl)-2-(4-aryl-1,3-thiazol-2-yl)hydrazine hydrochlorides. The protonation was accompanied by mutually dependent tautomeric rearrangements of heterocyclic fragments.     

Synthesis and Properties of 3-Alkyl(aryl)-5-chloromethylisoxazoles

3-Chloro-2-isothiocyanato-1-propenyl alkyl(aryl) ketones react with hydroxylamine hydrochloride to give 3-alkyl(aryl)-5-chloromethylisoxazole. Treatment of the latter with dimethylamine and ammonium thiocyanate leads to formation of previously unknown 3-alkyl(aryl)-5-dimethylamino(or isothiocyanato)- methylisoxazoles.     

Reaction of 2-(2-oxo-2-arylethylidene)-2,3-dihydropyrimidine-4(1H)-ones with aldehydes

2-(2-Oxo-2-arylethylidene)-2,3-dihydropyrimidine-4(1H)-ones react with aromatic and heteroaromatic aldehydes to form the unsaturated ketones, whereas in the case of 3- and 4-benzaldehydes the corresponding trans-2-styrylpyrimidine-4(3H)-ones were obtained. A possible mechanism of hydrolytic cleavage of the product of condensation of 2-(2-oxo-2-phenylethylidene)-2,3-dihydropyrimidine-4(1H)-one with paraformaldehyde under acid catalysis and mechanochemical activation has been discussed.     

Synthesis of Alkyl 4-(1-Alkyl-2-aryl-2-oxoethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates

Zinc enolates derived from 1-aryl-2-bromoalkanones react with alkyl 5,5-dimethyl-2-oxo-2,5-dihydrofuran-3-carboxylates to give alkyl 4-(1-alkyl-2-aryl-2-oxoethyl)-5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylates. Reactions of the latter with amines, such as p-toluidine, cyclohexylamine, and piperidine, lead to the corresponding carboxamides.     

Diastereoselective Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan catalyzed by bismuth triflate

We have developed an efficient vinylogous Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan with various aromatic aldehydes mediated by bismuth triflate in low catalyst loading (1 mol %). The reaction proceeds rapidly and affords the corresponding 5-(hydroxy(aryl)methyl)furan-2(5H)-ones in high yields with good to very good diastereoselectivities (dr up to >98:2). Such selectivities, albeit previously reported with other Lewis acids, could this time be achieved with a much lower catalyst loading. 5-(Hydroxy(alkyl)methyl)furan-2(5H)-ones derived from ketones could also be obtained with good diastereoselectivities.     

Synthesis of Alkyl 2-(1-t-Butylperoxyalkyl)propenoates and Ethyl 2-t-Butylperoxymethylbut-2-enoate

Methods of synthesis of alkyl 2-(1-t-butylperoxyalkyl)propenoates and ethyl 2-t-butylperoxymethylbut-2-enoate are developped through the nucleophilic substitution of t-butylperoxylate anion towards various allylic derivatives prepared from alkyl 2-hydroxymethylalk-2-enoates and ethyl 2-(1-hydroxyethyl)propenoate.