Free radical-mediated vinyl amination: a mild, general pyrrolidinyl enamine synthesis

The complete scope of free radical-mediated vinyl amination is described, using 5-exo-trig cyclizations of vinyl radicals to the nitrogen of azomethines. The focus is primarily on N,N-dialkyl enamines since their nucleophilicity renders them the most challenging enamines to synthesize using redox conditions. These studies establish several encouraging precedents for the broader application of this strategy.     

Free radical-mediated aryl amination: convergent two- and three-component couplings to chiral 2,3-disubstituted indolines

5-exo-trig Cyclization of an aryl radical to the nitrogen of an azomethine is used as the key annulating step in a modular preparation of 2,3-cis- and trans-disubstituted indolines. The precursors are readily prepared by phase-transfer-catalyzed Michael addition of a glycine Schiff base to a variety of acceptors. When the more reactive alkylidene malonate Michael acceptors are implemented, a one-pot three-component coupling is possible. The net result is a convergent [3 + 2] coupling strategy for the construction of highly functionalized indolines, a substructure occurring in numerous biologically active natural products.     

Palladium catalyzed amination of vinyl chlorides: a new entry to imines, enamines and 2-amino-1,3-butadienes

Vinyl chlorides are employed for the first time in palladium catalyzed cross-coupling reactions with amines to furnish imines and enamines. The new methodology has been applied to the synthesis of 2-amino-1,3-butadienes, that could not be achieved from the corresponding bromides.     

Palladium catalyzed alkenyl amination: from enamines to heterocyclic synthesis

The most recent advances in the Pd catalyzed amination of alkenyl halides directed towards the synthesis of imines and enamines are reviewed. The application of this cross-coupling reaction in the synthesis of heterocycles appears to be a potentially powerful methodology. The few examples already available are also discussed.     

An efficient solventless method for the synthesis of N,N-dialkyl sulfonamide derivatives

Aza-Michael addition of sulfonamides to α,β-unsaturated esters efficiently proceeds in the presence of catalytic amount of sodium hydroxide (NaOH) and tetrabutylammonium bromide (TBAB) as a phase-transfer catalyst (PTC) under microwave irradiation to afford N,N-dialkyl sulfonamides as biologically interesting compounds in good to excellent yields and short reaction times.     

Reactions ofN-nitramines and their trimethylsilyl derivatives withN,N-bis(trimethylsilyloxy)enamines

Trimethylsilyl derivatives of methyl- and ethylnitramine react asN-centered nucleophiles with 2-N,N-bis(trimethylsilyloxy)aminopropene to give trimethylsilyl derivatives of hitherto unknown α-(N-nitro)alkylamino-substituted acetone oximes. As an ambident nucleophile, nonsubstituted methylnitramine reacts with the same enamine to give both a product of N,C-corss-coupling and a product of O,C-cross-coupling,viz., N′-methyl-N-[(2-trimethylsilyloxyimino)propoxy]diazeneN-oxide. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2045–2047, October, 1998.     

Nature of reissert analogs derived from N,N-dialkyl and N,N-diaryl carbamoyl chlorides

Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method. Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.     

From vinyl sulfides, sulfoxides and sulfones to vinyl zirconocene derivatives

An easy and straightforward new method for the preparation of sp² zirconocene derivatives from a wide range of heterosubstituted alkenes such as vinyl sulfides, sulfoxides and sulfones is described. In all cases, a complete isomerization of the stereochemistry is observed and only the E-isomer is obtained. The reactivity of the resulting vinylic organometallic can be increased by a transmetalation reaction into organocopper, organozinc or organopalladium species and, therefore, several carbon-carbon formation were easily realized.     

Pd-catalyzed stereoselective tandem ring-opening amination/cyclization of vinyl γ-lactones: access to caprolactam diversity

A stereoselective amination/cyclization cascade process has been developed that allows for the preparation of a series of unsaturated and substituted caprolactam derivatives in good yields. This conceptually novel protocol takes advantage of the easy access and modular character of vinyl γ-lactones that can be prepared from simple precursors. Activation of the lactone substrate in the presence of a suitable Pd precursor and newly developed phosphoramidite ligand offers a stereocontrolled ring-opening/allylic amination manifold under ambient conditions. The intermediate (E)-configured ε-amino acid can be cyclized using a suitable dehydrating agent in an efficient one-pot, two-step sequence. This overall highly chemo-, stereo- and regio-selective transformation streamlines the production of a wide variety of modifiable and valuable caprolactam building blocks in an operationally attractive way.

A Pd-mediated stereoselective tandem process has been developed towards a large variety of functional caprolactam synthons.     

Efficient access to some new pyrimidine derivatives and their antimicrobial evaluation

1-[4-(3-Hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]ethanone ( 1 ) was used as a precursor for heterocyclic synthesis. Condensation of compound 1 with monochloroacetic acid and benzaldehyde gave thiazolopyrimidine 2 which in turn underwent cyclization with malononitrile dimmer to afford malononitrile derivative 3 . Also, the reaction of compound 1 with benzaldehyde under a basic condition produced chalcone 4 . Chalcone 4 can be used as a key intermediate for further preparation of heterocyclic compounds. In addition, compound 1 was allowed to react with malononitrile dimmer and/or ethyl chloroacetate to give pyrimidines 8 and 9 , respectively. Alkylation of compound 8 with ethyl chloroacetate afforded S-alkylated product 10 which was treated with hydrazine hydrate to yield the hydrazino derivative 11 . Alternative synthesis of compound 10 was taken place through reaction of compound 9 with malononitrile dimmer. The biological activity of the synthesized compounds was investigated. Compounds 1 , 4 , 5 , and 8 recorded high activities against Gram positive bacteria (S. aureus). Structures of the new synthesized compounds were elucidated by elemental analysis and spectral data.     

Gas Chromatographic Determination of Sodium N,N-dialkyl Dithiocarbamates such as their S-n-propyl Esters in Industrial Wastewater

Abstract

A gas chromatographic method for the determination of N,N-dialkyl dithiocarbamates in industrial wastewater at the nanogram level is described. The sample is freeze-dried, extracted with ethanol and then esterified with 1-iodopropane. The method is sensitive, specific, and free from interference of metals. The sensitivity of the method is in the order of 1 ng (injected).     

Free radical-mediated aryl amination and its use in a convergent [3 + 2] strategy for enantioselective indoline alpha-amino acid synthesis

The scope of aryl radical additions to the nitrogen of azomethines is described. Aryl, trifluoromethyl alkyl, and alpha,beta-unsaturated ketimines engage in regioselective aryl-nitrogen bond formation via 5-exo cyclizations of an aryl radical to azomethine nitrogen. Selectivity for carbon-nitrogen over carbon-carbon bond formation is generally high (>95:5) and competes only with direct aryl radical reduction by stannane (0-10%). Alpha-ketoimines are a promising new class of carbon radical acceptors for which no competitive aryl radical reduction is observed. The reaction conditions are pH-neutral and are therefore among the mildest methods available for amination of an aromatic ring. The ketimines examined did not suffer from competitive reduction by stannane, offering an advantage over the use of diazo and azide functional groups as nitrogen sources for carbon radicals. The free radical-mediated aryl amination was sequenced with the O'Donnell phase transfer-catalyzed enantioselective alkylation strategy of glycinyl imine to provide either enantiomer of indoline alpha-amino acids with high ee. These new constrained phenyl alanine derivatives are now readily available for evaluation across a variety of applications.     

Mass spectral studies of a series of N,N-dialkyl aminoethyl-2-chlorides and trimethyl silyl ethers of N,N-dialkyl aminoethane-2-ols under electron impact conditions

The electron impact (EI) mass spectra of a series of N,N-dialkyl-aminoethyl-2-chlorides, N(R(1))(R(2))-CH(2)-CH(2)Cl and trimethylsilyl ethers of N,N-dialkyl aminoethane-2-ols, N(R(1))(R(2))-CH(2)-CH(2)-O-Si(CH(3))(3), where R(1) and R(2) = methyl, ethyl, propyl and isopropyl, which are precursors of VX type of compounds, are studied. All the compounds (1-20) show abundant molecular ions, in addition to a weak [M - H](+) ion, except the N,N-diisopropyl group containing compounds (8 and 18). A general EI fragmentation pattern for the above two series of compounds is discussed. The observed fragment ions are due to simple homolytic cleavages, and they are distinct to allow the identification of the compounds unequivocally including those of isomeric compounds. The primary fragmentation of compounds 1-20 is beta-cleavage, i.e. homolytic cleavage of C-C bond, which is linked to the nitrogen atom. Three types of beta-cleavages are possible for these compounds, in which the abundance of beta-cleavage product ions is found to depend on the size and structure of the alkyl group attached to nitrogen. The alpha-cleavage fragment ions are found only for N,N-dialkyl aminoethyl-2-chlorides but are absent in the corresponding trimethylsilyl ethers of N,N-dialkyl aminoethane-2-ols. The retention indices are calculated for all the studied compounds (1-20) and are in the ranges of 750.38-1079.24 for 1-10 and 905.23-1190.25 for 11-20.     

Photocatalytic divergent decarboxylative amination: a metal-free access to aliphatic amines and hydrazines

Nitrogen-containing motifs are widely present in natural products, bioactive molecules, and drugs. Accordingly, effective synthetic methods with high efficiency and diversity are highly desirable. Here, we present the invention of a facile, visible lightmediated decarboxylative C(sp~3)–N bond-forming reaction by employing abundant carboxylic acids as the feedstock and a commercial diazirine as a nitrogen donor. This process is amenable to access both imines and diaziridines, as the corresponding masked amines and hydrazines, through a selectable single or double nitrogen transfer from the diazirine, respectively. This divergent approach works well in both directions with various alkyl carboxylic acids, including primary, secondary, and tertiary acids, as well as natural products and drugs, thus affording a rapid, metal-free approach to build nitrogen-containing molecule libraries with considerable structural diversity, which could thus benefit the related study in context of chemical biology and drug discovery.     

N,N-Disubstituted-4-aminophenylazostyrylformate derivatives: their synthesis, mesogenic behaviour and photostability

A series of new azo dye liquid crystals was prepared by the reaction of the N,N-disubstituted-4-aminophenylazobenzaldehydes with butyl cyanoacetate in the presence of piperidine in refluxing ethanol. The new azo dye liquid crystals possess a SmA phase, and representative samples were found to be reasonably photostable.     

N-haloamidines—III: S-Triazine derivatives from N-halobenzamidines and enamines

The reaction of N-haloamidines with enamines affords 1,4-dihydro-s-triazine derivatives as the main reaction product. The dihydro derivatives are aromatisable through oxidation with chloranil. The mass spectra of the isolated products are discussed in detail.