Reactions of Dimethyl Heteroaroylphosphonates with Trialkyl Phosphite in the Presence of Proton Donors

Abstract

We have previously shown that substituted bcnzoylphosphonates (1; Ar ? X-Ph) react with trimethyl phosphite to give anionic intermediates which in the absence of electrophiles decompose to give carbene intermediates (3). The nature of the subsequent reaction products depends on the type and position of the substituents on the aromatic ring.ll1 When proton donors are present the initially formed anionic intermediates (2) give the quasi-phosphonium salts (4) which usually decompose to give the phohphonate-phosphates (5). although for the case of (1; Ar ? 4-MeOPh) formation of the phosphonates (6) was observed.     

Studies of the Reactions of 2-Substituted Dimethyl Benzoylphosphonates with Trimethyl Phosphite

Abstract

Dimethyl benzoylphosphonates (1) react with trimethyl phosphite to give anionic intermediates (2) which decompose to give carbenes (3) and trimethyl phosphate [1]. When suitable ortho-substituents are present on the benzoylphosphonate, intramolecular carbene insertion reactions can occur to give cyclic systems. With alkyl substitutents, where the length of the chain provides a choice of cyclisation pathways, insertion into an appropriate C[sbnd]H bond to give a 5-membered ring has been found to be the preferred option. We have therefore been investigating the behaviour of systems, such as (4), where insertion into a C[sbnd]H bond to give a 5-membered ring is prevented.     

Furanolates 1. A General Preparation of Alkyl Furyl Carbonates

Trimethylsiloxyfuran reacts with methyllithium to give lithium fura-nolate and unreactive tetramethylsilane, the former reacts with alkyl chloroformates on oxygen to give alkyt furyl carbonates not previously easily prepared.     

Reactions of 4-pyrones with primary amines. A new class of ionic associates

Primary aliphatic amines react with 2,6-dimethyl-4-pyrone to give 2,6-dialkylamino-2,5-heptadien-4-one derivatives. When the alkyl group was methyl, the diamino derivative cyclized on warming to give 1,2,6-trimethyl-4-pyridone. The corresponding butylamino derivative did not thermally cyclize, but did give a pyridone on treatment with acid. The isopropylaminoketone did not cyclize. Several examples of 1,2,6-trisubstituted-4-pyridones formed “ionic associates” consisting of two parts of the pyridone and one part of perchloric acid. These associates are useful primary standards for nonaqueous titrations.     

Application of aryloximes as solid-phase ketone linkers

In both solution and the solid phase, a variety of ketone oxime anions have been treated with 4-substituted-2-fluorobenzonitriles to give the corresponding nucleophilic aromatic substitution aryloxime adducts. Under aqueous acidic conditions, these adducts underwent cyclization to give the corresponding ketones. Suzuki and amide coupling reactions were also successfully performed on two resin-bound oximes followed by subsequent cyclorelease to give ketone product in good yields and purities. [reaction--see text]     

Reactions of Trimethylsilyl Isocyanate with Alcohols and Phenols

Mono- and diphenols add to trimethyl isocyanate on heating to give the corresponding aryl urethanes. Ethanol reacts with trimethylsilyl isocyanate to give ethyl urethane and ethyl allophanate in a ratio determined by reaction conditions.     

Halogenation of Xanthenyl and Thioxanthenylallenes

Reactions of acids with vinylidenexanthenes (or thioxanthenes) 1 and 9-methoxy-9-vinylxanthenes (or thioxanthenes) 8 give xanthene- (or thioxanthene-) 9-spiro-1′-indenes 7 . With bromine or sulfuryl chloride they give the corresponding 2′-halogenoxanthene- (or thioxanthene-)9-spiro-1′-indenes 5 . Formation of such derivatives depends on preferential attack of the reagents on allenes 1 to give initially xanthylium (or thioxanthylium) ions 3 which cyclize. One π bond of the allenes 1 can be selectively reduced in acid media. Chemical and spectral evidence for these routes are presented.     

Asymmetric synthesis of cis- and trans-2,5-disubstituted pyrrolidines from 3-oxo pyrrolidine 2-phosphonates: synthesis of (+)-preussin and analogs

Pyrrolidine enones, derived from 3-oxo pyrrolidine 2-phosphonates and a HWE reaction with aldehydes, on Luche reduction give pyrrolidine allylic alcohols. The alcohols on hydrogenation (Pd/H2) give cis-2,5-disubstituted pyrrolidines and on treatment with TFA-NaBH3CN undergo a hydroxy directed reduction to trans-2,5-disubstituted pyrrolidines.     

The effect of nitro groups on oxidative cyclisation of chalcones by thallium(III) nitrate(TTN)

2′-Hydroxy-3′-nitrochalcones on oxidation with thallium(III) nitrate do not give rearranged intermediates that can give isoflavones, instead cyclisation gives benzyl-idenebenzofuran-3(2H)-one derivatives.     

Insertion reactions of alkenes with diterpenoid chromium aminocarbenes

Insertion reactions of electron-deficient alkenes with chromium aminocarbenes derived from podocarpic acid generally give aryl ketone products derived from ring opening of an aminocyclopropane and subsequent enamine hydrolysis, the exception being alkenyl sulphones which give products derived from insertion of the carbene into the β-CH bond of the alkene. Increasing steric hindrance due to the substituents on the aminocarbene nitrogen appears to result in higher yields of the insertion products. However, other factors such as stabilisation of the intermediate tetracarbonylaminocarbene may explain why morpholinocarbenes give superior yields of the insertion products. Propenoic acid, propenal or nitropropene give a 13-formyl-substituted diterpenoid. Electron-rich alkenes do not undergo insertion reactions with these aminocarbenes at 110°C.     

Synthesis of mercaptonitroimidazoles and their reaction with 2,4,6-trinitrochlorobenzene

A number of derivatives of mercaptomono- and dinitroimidazoles were synthesized by the action of potassium sulfide on the corresponding halonitroimidazoles. Mono- and dipotassium salts of mercaptonitroimidazoles were obtained. It was established that the monopotassium salts of mercaptomono- and dinitroimidazoles react with 2,4,6-trinitrochlorobenzene to give picrylmercapto derivatives, dipotassium salts of mononitromercaptoimidazoles give, depending on the ratio of the components, picrylmercaptonitroimidazoles or S.N-dipicrylmercaptonitroimidazoles, and dipotassium salts of mercaptodinitroimidazole give only picrylmercaptonitroimidazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 812–816, June, 1982.     

Cycloaddition reactions of polyfluoroalkylthioncarboxylic acid derivatives with dimethyl acetylenedicarboxylate (DMAD)

Polyfluoroalkyldithiocarboxylates react with dimethyl acetylenedicarboxylate (DMAD) to give 2-polyfluoroalkyl-1,3-dithioles and/or 2-polyfluoroalkylidene-1,3-dithioles depending on the substituent at the thiolic sulfur atom and on the length of the polyfluoroalkyl chain. Amides of polyfluoroalkylthioncarboxylic acids with DMAD give 2-methoxy-2-polyfluoroalkyl-5-methoxycarbonylmethylene-thiazolidin-4-ones.     

About the Synthesis of Heterocyclic Analogues of Marginalin and Their Transformation Products

Pyridine-2 or 4-carboxaldehyde, furan-2-aldehyde, were condensed on 2-coumaranone and on 5-hydroxy 2-coumaranone to give new ene-lactones analogues of the natural marginalin. Only the addition compounds issued from 2-coumaranone could give stilbene methyl esters and no rearrangement into benzo [b] furan carboxylates could be observed. These observations are discussed in relation with previous results in the series.     

Addition reactions of 2-polyfluoroalkyl substituted 1,3-thiazolin-4-one derivatives

2-Polyfluoroalkyl-5-methoxycarbonylmethylene-thiazolin-4-ones react as dienophiles on the exo-cyclic ylidene bond to give spiro-derivatives and as 1,3-dienes with olefins to give dihydropyranothiazole derivatives. The endo-cyclic CN bond in these compounds do not enter into the cycloaddition reactions.     

The reactions of perfluoroalkanesulfonyl bromide with hetero-atom substituted olefinic bonds

Perfluoroalkanesulfonyl bromides reacted with vinyl bromide, vinyl acetate and trimethyl vinyl silane to give the corresponding adducts with the evolution of SO₂. Perfluoroalkanesulfonyl bromide reacted with trimethyl silyl enol ether followed by hydrolysis to give the corresponding α-bromoketones and perfluoroalkanesulfinic acid. However, perfluoroalkanesulfonyl chlorides reacted with trimethyl silyl enol ether of pinacolone on UV irradiation to give the corresponding α-perfluoroalkyl derivatives of pinacolone. Under mild condition, perfluoroalkanesulfonyl bromide also brominated phenol and anisole to give the corresponding p-bromo derivatives. Sodium α, α-dichlorotrifluoroethanesulfinate reacted with bromine in water at 25°C to form α, α-dichlorotrifluoroethanesulfonyl bromide which was thermally less stable than but similar in reactivity to perfluoroalkanesulfonyl bromide.     

A novel class of nitrile ylide

Isothiocarbamoyl chlorides IV on treatment with NEt₃ afforded nitrile ylides V which reacted with dimethyl acetylenedicarboxylate to give 2H-pyrroles VI and with ethyl cyanoformate to give 4H-imidazoles VII.     

The diene synthesis with sulfur-containing derivatives of acrylic acids

Reaction of aqueous solutions of salts of acrylic acids with thioepi chlorohydrin affords thietyl acrylates, which on hydrolysis give 3-hydroxythietane, and on oxidation with hydrogen peroxide give 3-hydroxythietane 1,1-dioxide. The diene synthesis was carried out with these acrylates, and also with acryloyl and methacryloyl isothiocyanates.The authors thanks M. I. Mironova for the IR spectra and the elemantal analyses.     

Tandem reactions of 1,3-diacid chlorides with 2-methylimidazoline and 2-methyl-1,4,5,6-tetrahydropyrimidine: one-pot synthesis of 1,8-naphthyridinetetraones

The reactions of 2-methylimidazoline and 2-methyl-1,4,5,6-tetrahydropyrimidine with 1,3-diacid chlorides, in the presence of Et3N in refluxing MeCN give highly functionalized potentially bioactive 1,8-naphthyridinetetraones. 2-Methylimidazoline and 2-methyl-1,4,5,6-tetrahydropyrimidine can be viewed as tridentate nucleophiles which give four consecutive tandem nucleophilic attacks on electrophiles.     

Novel heterocycles. 7. Reaction of 2-chloronicotinonitrile with thioureas. Synthesis of the pyrido[2,3-d]pyrimido-[2,1-b][1,3]thiazine ring system

N,N'-Dimethylthiourea and 3,4,5,6-tetrahydro-2-pyrimidinethiol were allowed to react with 2-chloro-nicotinonitrile ( 1 ) and their products investigated by standard methods and by carbon-13 nmr. In both instances, displacement of the chlorine occurred by nitrogen not the sulfur of the thioureas. Secondary cyclizations occurred by attack of nitrogen on the nitrile to furnish 3a , and by sulfur on the nitrile to give 4b , a new ring system. Tricyclic 4b was hydrolyzed in dilute acid to give 5 , or alkylated with methyl iodide in the presence of sodium hydride to give the ring opened product 6 .     

Synthesis and properties of 3-thiono derivatives of pyrido[2,3-e]-asym-triazine

2-Amino-3-hydrazinopyridine reacts with carbon disulfide to give 1,2,3,4-tetrahydropyrido[2,3-e]-asym-triazine-3-thione. The methylthio derivative obtained from it is oxidized to the sulfone, which undergoes exchange of the methylsulfonyl group for an amine residue in the cold. The methylthio derivative undergoes this sort of reaction only on heating, whereas in the cold it reacts with amines to give adducts that are unstable in solution and on heating.