Phase-transfer Catalyzed Alkylation Research Articles

Phase-transfer-catalyzed alkylation of guanidines by alkyl halides under biphasic conditions: a convenient protocol for the synthesis of highly functionalized guanidines.

An operationally straightforward and efficient method for the alkylation of carbamate-protected guanidines with various alkyl halides and mesylates is described. This protocol proceeds via deprotonation of the acidic N-carbamate hydrogen of the guanidine under biphasic conditions using a catalytic amount of a tetrabutylammonium salt as a phase-transfer catalyst. In this manner, highly functionalized guanidines can be obtained. The reaction is tolerant of a wide range of functional groups on both the alkyl halide and guanidine component. In addition, the reaction is sufficiently mild such that simple aqueous workup and filtration through a short silica gel column yields the substituted guanidines in high purity. In conjunction with the EDCI-mediated guanylation of disubstituted thioureas with amines, phase-transfer catalyzed alkylation of guanidines via a one-pot, three-component synthesis of substituted guanidines was achieved.

Spiropyrans and spirooxazines. 1. Synthesis and photochromic properties of 9"-hydroxy- and 9"-alkoxy-substituted spironaphthooxazines

A procedure was developed for phase-transfer catalyzed alkylation of 5-hydroxyindolenine and 9"-hydroxy-substituted spiro[indoline-2,3"-naphtho[2,1-b]oxazines] by alkyl halides. New 9"-hydroxy- and 9"-alkoxy-substituted spironaphthooxazines, spirooxazinyloxyacetic acids, and their esters containing substituents with different length of the carbon chain in the indoline moiety were synthesized. The influence of the substituents on the spectroscopic properties of the starting and colored forms and the kinetic characteristics of photochromic transformations of 9"-substituted spironaphthooxazines in solutions and polymeric films was investigated. The bipolar merocyanine forms of spirooxazines were found to produce H-aggregates.

The preferred solid‐state conformation of (αMe)Trp peptides

The two Z-L-Ala-DL-(alpha Me)Trp-NH2 diastereomeric dipeptides were synthesized from (Z-L-Ala)2(O) and H-DL-(alpha Me)Trp-NH2. The latter racemate, prepared by phase-transfer catalyzed alkylation of the N alpha-benzylidene derivative of alanine amide followed by acidic hydrolysis of the resulting Schiff base, was characterized by X-ray diffraction. The molecular and crystal structure of Z-L-Ala-L-(alpha Me)Trp-NH2, separated from its diastereomer by silica-gel column chromatography, was determined by X-ray diffraction analysis. Both independent molecules in the asymmetric unit of the dipeptide adopt a type-II beta-bend conformation. However, only the more regularly folded conformation of molecule B is stabilized by a 1<--4 C = O...H--N intramolecular H bond. The present results indicate that: (i) the C alpha-methylated (alpha Me)Trp residue is a strong beta-bend and helix former, and (ii) the relationship between (alpha Me)Trp chirality and helix screw sense tends to be opposite to that of protein amino acids. The implications for the use of the (alpha Me)Trp residue in designing conformationally restricted analogs of bioactive peptides are briefly discussed.

Syntheses of 2-oxabicyclo[4.10.0]hexadec-1(6)-ene from cyclododecanone

Two methods for the synthesis of 2-oxabicyclo[4.10.0]hexadec-1(6)-ene from cyclododecanone have been suggested. The most convenient method involves the preparation of 2-(3-tert-butoxypropyl)cyclododecanone by phase-transfer catalyzed alkylation of cyclododecanone with l-bromo-3-tert-butoxypropane followed by removal of the protectingtert-butyl group and elimination of water.

1,5-Benzodiazepines XI. 5-(Dialkylamino) or 5-(alkylthio) substituted 8-chloro-6-phenyl-6 H-[1,2,4]triazolo[4,3- a][1,5]benzodiazepines with anticonvulsant activity

The cyclocondensation of (dimethylamino)benzodiazepinones 3a,b with hydrazides yielded triazolobenzodiazepinones 4 which were treated with Lawesson's reagent to give thiolactams 5. The phase-transfer catalyzed (TEBA) alkylation of compounds 5 with suitable alkyl halides afforded 5-(alkylthio)-6-phenyl-6 H-[1,2,4]triazolo[4,3- a][1,5]benzodiazepines 6a-f. The desired N,N-dialkyl-6-phenyl-6 H-[1,2,4]triazolo[4,3- a][1,5]benzodiazepin-5-amines 7a-k were finally obtained from the reaction of the (methylthio)derivatives 6a-d with proper dialkylamines. Compounds 6b-f and 7a-e, g-k were screened for anticonvulsant activity after a preliminary evaluation of their gross behavioral effects and acute toxicity. Nine of the 15 triazolobenzodiazepines tested exerted a clear-cut anticonvulsant effect associated with low acute toxicity. In particular, the most active compounds 6e, f and 7h showed LD 50/ED 50 ratios that were notably higher than that of phenobarbital and ranging from 50% to 20% of that of diazepam, the latter used as reference drugs.

Synthesis of α,α-disubstituted α-amino acid amides by phase-transfer catalyzed alkylation

α,α-Disubstituted α-amino acid amides were prepared in 17–86% chemical yield by the phase-transfer catalyzed alkylation of N-benzylidene α-H amino acid amides, followed by weak acidic hydrolysis of the Schiff bases.

A catalytic enantioselective synthesis of α-methyl amino acid derivatives by phase-transfer catalysis

Optically active α-methyl amino acid derivatives are prepared in up to 50% enantiomeric excess by phase-transfer catalytic alkylation of aldimine Schiff bases of alanine t-butyl ester.

Alkylation of 2-Acetylpyrrole and 1 -alkyl-2-Acetylpyrroles Under Solid/Liquid Phase-Transfer Conditions

Abstract The alkylation of 2 -acetylpyrrole with alkyl iodides in the benzene/solid KOH system in the presence of 18-crown-6 at room temperature gives the corresponding 1-alkyl derivatives in high yields. The phase-transfer catalysed alkylation of 1-alkyl-2-acetylpyrroles without solvent leads to side-chain di-C-alkylated products, i.e. ketones of the (1-alkyl-2-pyrrolyl) COCHR2 type in satisfactory yields.

ChemInform Abstract: Phase-Transfer Catalytic Alkylation of Hydroperoxides: A Convenient Route to Mixed Dialkyl Peroxides.

Abstract The solid-liquid phase transfer catalytic alkylation of hydroperoxides using solid potassium hydroxide as a base and TEBAC as a phase transfer catalyst is reported. When the alkylating agent is a primary bromide, this reaction represents a simple and quick method for the synthesis of mixed dialkyl peroxides in fair yields.

Phase-Transfer Catalytic Alkylation of Hydroperoxides: A Convenient Route to Mixed Dialkyl Peroxides

Abstract The solid-liquid phase transfer catalytic alkylation of hydroperoxides using solid potassium hydroxide as a base and TEBAC as a phase transfer catalyst is reported. When the alkylating agent is a primary bromide, this reaction represents a simple and quick method for the synthesis of mixed dialkyl peroxides in fair yields.

Studies in [3,4] sigmatropic rearrangements: a novel synthesis of 9-allenyl-10-substituted anthracenes from 10,10-disubstituted 9-anthrols

A series of 10,10-disubstituted anthrones (3a–f) have been prepared from anthrone (1) and 10-prop-2-ynylanthrone (2) by both phase-transfer catalysed alkylation and classical alkylation. Reduction of these compounds with sodium borohydride in methanol gave a series of 10,10-disubstituted anthrols (6a–f). These when heated in acetic acid underwent smooth rearrangement to give 9-allenyl-10-alkyl (and related alkenyl and alkynyl) anthracenes (7a, b, e, f) except for 10,10-dibut-2-ynyl (6c) and 10,10-dibut-2-enyl-9-anthrol (6d) where the corresponding acetates (8c, d) were obtained. This reaction was also studied in the presence of a small amount of trifluoroacetic acid (TFA) and toluene-p-sulphonic acid (TPSA). In the presence of the former in carbon tetrachloride the reaction was complete in 5 min at 0–5 °C. The migratory aptitude of groups and the mechanism of the reaction is commented on.

Phase-transfer catalyzed alkylation of pyrazoles and 1,2,4-triazole with cis- and trans-1,4-dichloro-2-butenes

The phase-transfer catalyzed (PTC) alkylation of pyrazoles and 1,2,4-triazole with cis- and trans-1,4-dichloro-2-butenes (DCB) has been examined. The monoalkylation products of pyrazoles with cis-DCB are bicyclic salts formed by intramolecular cyclization of the intermediate cis-1-(4-chloro-2-butenyl)pyrazoles. The corresponding trans-compounds are incapable of cyclization, but on prolonged standing they undergo intermolecular polyquaternization. Both cis- and trans-DCB undergo phase-transfer catalyzed reaction with 1,2,4-triazole to give polymeric quaternary salts. Conditions have been worked out for the dehydrochlorination of 1-(4-chloro-2-butenyl)azoles to 1-(butadien-2-yl)azoles.

Studies on Organophosphorus Compounds XXXIII. Chemoselective Phase-Transfer CatalyticS-Alkylation of Dialkyl/diarylthiophosphinic Acids; A New Facile Route toS-Alkyl Dialkyl/diarylthiophosphinates

A phase-transfer catalytic (PTC) alkylation involving the reaction of alkyl bromide and dialkyl/diarylthiophosphinic acids in the presence of potassium carbonate and tetrabutylammonium bromide is described. The reaction proceeds by SN2 mechanism and gives exclusively S-alkylated products.

A Two-Step Synthesis of Mimosamycin

Abstract The marine antibiotic mimosamycin, and a number of analogues, have been prepared in two steps by cycloaddition of a 1,4-benzoquinone or naphthoquinone with 2-aza-bis(1,3-t-butyldimethylsilyloxy)-1,3-buta-diene, hydrolytic work-up of the adduct, and phase-transfer catalysed alkylation of the resultant isoquinolin-3-ones.

Phase transfer catalysis under ultrasound. Alkylation of isoquinoline Reissert compound

Comparative experiments showed that ultrasonic irradiation improved the yields and reduced times in the phase-transfer catalysed alkylation of the Reissert compound 2-benzoyl-1,2-dihydroisoquinoline-1-carbonitrile.

Preparation of isopropyl- and t-butyl-pyridines from methylpyridines by phase-transfer catalysed alkylation

Methyl groups in the 2,4, and 6 positions of pyridine rings have been converted into isopropyl (2 and 6 positions) and t-butyl (4 position) groups by alkylation of the N-methylpyridinium iodides with methyl iodide, using a phase-transfer catalyst; attempts to prepare 2,6-diethylpyridine, or to alkylate 3-methylpyridine, by this technique were unsuccessful.

ASYMMETRIC SYNTHESIS OF 3-SUBSTITUTED 3,4-DIHYDRO-β-CARBOLINONES

Abstract A novel method of phase-transfer catalysed alkylation at C-3 position of 3,4-dihydro-β-carbolinones and an asymmetric synthesis of (S)-3-carbomethoxymethyl-9-methyl-3,4-dihydro-β-carbolinone (7) are reported.