Showing papers on "Alkylation published in 1985"

The Chemistry of Hydantoins

Abstract: Publisher Summary This chapter reviews the chemistry of hydantoins. The hydantoins can be synthesized using amino acids, cyanate or thiocyanate salts, alkyl or aryl isocyanates and isothiocyanates, ureas, α-dicarbonyl compounds, Bucherer–Bergs and Read reactions, and cycloaddition reactions with heterocumulenes. The chapter also illustrates physicochemical studies on hydantoins. H-NMR, IR, and UV techniques are widely used to study ionization and tautomerism in hydantoins. Hydantoins are weak acids which owe their acidic character to dissociation of the proton bonded to the 3-nitrogen atom as this allows for maximum delocalization of charge in anion. The chapter also presents physicochemical studies on hydantoins using ultraviolet spectroscopy, mass spectrometry, infrared spectroscopy, nuclear magnetic resonance spectroscopy, crystal structure determinations, and quantum mechanical calculations. The reactivity of hydantoins and their derivatives are described further in the chapter. Hydantoins and thiohydantoins can react with nucleophilic and electrophilic as well as with other types of reagents. On protonation in a strongly acidic solution, hydantoin cations are formed. Hydantoins can easily be alkylated in the N-3 position by treatment with alkyl halides in an alkaline solution in protic or aprotic solvents. Other alkylating agents include dimethyl sulfate and diazomethane.

Asymmetrische Michael‐Additionen. Stereoselektive Alkylierung chiraler, nicht racemischer Enolate durch Nitroolefine. Herstellung enantiomerenreiner γ‐Aminobuttersäure‐ und Bernsteinsäure‐Derivate

Abstract: Asymmetric Michael-Additions. Stereoselective Alkylation of Chiral, Non-racemic Enolates by Nitroolefins. Preparation of Enantiomerically Pure γ-Aminobutyric and Succinic Acid Derivatives Chiral, non-racemic lithium enolates (E,F,G) of 1,3-dioxolan-4-ones, methyl 1,3-oxazolidin-4-carboxylates, methyl 1,3-oxazolin-4-carboxylates, 1,3-oxazolidin-5-ones, and 1,3-imidazolidin-4-ones derived from (S)-lactic acid (2a), (S)-mandelic acid (2b), and (S)-malic acid (2c), or from (S)-alanine (10), (S)-proline (11), (S)-serine (12), and (S)-threonine (13), are added to nitroolefins. Michael adducts (3–9, 14–18) are formed (40–80%) with selectivities generally above 90% ds of one of the four possible stereoisomers. Conversions of these nitroalkylated products furnish the α-branched α-hydroxysuccinic acids 28 and 29, the α-hydroxy-γ-amino acid 25, the α,γ-di-amino acid 32, the substituted γ-lactames 19–22, and the pyrrolidine 23. The relative and absolute configuration of the products from dioxolanones and nitropropene are derived by chemical correlation and NOE measurements indicating that the steric course of reaction is to be specified as 1k, ul-1,3. The mechanism is discussed.

Substituted Ureas. Methods of Synthesis and Applications

Abstract: Systematic data on the method of synthesis of ureas by the interaction of compounds containing the amino-group with organic isocyanates, of amines and alkyl halides with alkali metal cyanates, and of primary and secondary amines with phosgene, carbon dioxide, urea, or nitrourea and by the carbonylation of amines are presented. The reactions involving the alkylation of urea and its interaction with various compounds containing functional groups are considered. The advantages and disadvantages of various methods are noted. The principal and practical applications of substituted ureas, including their applications as additives to organic materials, are discussed. The bibliography includes 314 references.

In vivo formation and persistence of modified nucleosides resulting from alkylating agents

Abstract: Alkylating agents are ubiquitous in the human environment and are continuously synthesized in vivo. Although many classes exist, interest has been focused on the N-nitroso compounds, since many are mutagens for bacteria, phage, and cells, and carcinogens for mammals. In contrast to aromatic amines and polyaromatic hydrocarbons which can react at carbons, simple alkylating agents react with nitrogens and oxygens: 13 sites are possible, including the internucleotide phosphodiester. However, only the Nnitroso compounds react extensively with oxygens. In vivo, most possible derivatives have been found after administration of methyl and ethyl nitroso compounds. The ethylating agents are more reactive toward oxygens than are the methylating agents and are more carcinogenic in terms of total alkylation. This is true regardless of whether or not the compounds require metabolic activation. It has been hypothesized that the level and persistence of specific derivatives in a "target" cell correlates with oncogenesis. However, no single derivative can be solely responsible for this complex process, since correlations cannot be made for even a single carcinogen acting on various species or cell types. Some derivatives are chemically unstable, and the glycosyl bond is broken (3- and 7-alkylpurines), leaving apurinic sites which may be mutagenic. These, as well as most adducts, are recognized by different enzymatic activities which remove/ repair at various rates and efficiencies depending on the number of alkyl derivatives, as well as enzyme content in the cell and recognition of the enzyme. Evaluation of human exposure requires early and sensitive methods to detect the initial damage and the extent of repair of each of the many promutagenic adducts.

α‐Alkylation of Amino Acids without Racemization. Preparation of Either (S)‐ or (R)‐α‐Methyldopa from (S)‐Alanine

Abstract: Enantiomerically pure cis- and trans-5-alkyl-1-benzoyl-2-(tert-butyl)-3-methylimidazolidin-4-ones (1, 2, 11, 15, 16) and trans-2-(tert-butyl)-3-methyl-5-phenylimidazolidin-4-one (20), readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf.3, 4, 12, 21). Diastereoselective alkylation of these enolates to 5,5-dialkyl- or 5-alkyl-5-arylimidazolidinones (5, 6, 9, 10, 13a-d, 17, 18, 22) and hydrolysis give α-alkyl-α-amino acids such as (R)- and (S)-α-methyldopa (7 and 8a, resp.), (S)-α-methylvaline (14), and (R)-α-methyl-methionine (19). The configuration of the products is proved by chemical correlation and by NOE 1H-NMR measurements (see 23, 24). In the overall process, a simple, enantiomerically pure α-amino acid can be α-alkylated with retention or with inversion of configuration through pivaladehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined ‘self-reproduction of a center of chirality’. The method is compared with other α-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, α-branched α-amino acids as synthetic intermediates and for the preparation of biologically active compounds is discussed.

Synthesis of sulfones by phase-transfer alkylation of arenesulfinate salts

Abstract: Alkylation a l'aide d'halogenures d'alkyle en presence d'halogenures de tetrabutylammonium dans un melange eau-benzene et acetone

Synthesis and biological activity of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids. A new class of heteroatom-activated beta-lactam antibiotics.

Abstract: The synthesis of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids (1) is described. 3-[(Carbobenzyloxy)amino]-N-hydroxy-2-azetidinones (13a,b), prepared from serine and threonine, were alkylated with 2-(trimethylsilyl)ethyl bromoacetate in the presence of potassium carbonate in THF/H2O. Alkylation with secondary alpha-bromo esters was accomplished with potassium hydroxide in dimethyl sulfoxide. The Cbz group was replaced with the 2-(2-amino-4-thiazolyl)-2(Z)-(methoxyimino)acetamido side chain by catalytic hydrogenation followed by treatment with 21. Removal of the 2-(trimethylsilyl)ethyl ester with fluoride ion provided derivatives suitable for antimicrobial evaluation. In vitro tests showed that the title compounds possess significant activity predominantly against Gram-negative bacteria.

The role of lithium salts in controlling the regiochemistry of the alkylation of a lithium enolate in a weakly polar aprotic solvent

Abstract: Etude de la methylation de l'isobutyrophenone par le toluenesulfonate de methyle dans le dioxolanne en presence de sels de lithium

Synthesis of novel dihydropyrimidines and tetrahydropyrimidines

Abstract: A partir d'α-acetyl cinnamates et d'amidines ou de guanidines, synthese d'hydroxy-6 tetrahydro-1,4,5,6 pyrimidinecarboxylates-5 qui sont ensuite deshydrates en derives dihydro. Alcoxycarbonylation, acylation et alkylation regioselectives en derives substitues en 3; reduction des derives obtenus en derives tetrahydro-1,2,3,4

Alkylierung in der 2‐Stellung von (2S, 4R)‐ 4‐Hydroxyprolin unter Retention

Abstract: Alkylation in the 2-Position of (2S, 4R)-4-Hydroxyproline with Retention of Configuration O-Acetyl-4-hydroxyproline (1b) is condensed with pivalaldehyde to give a single stereoisomer of the 2-(tert-butyl)-4-oxo-3-oxa-1-azabicyclo[3.3.0]oct-7-yl acetate (3). This is converted to the enolates 4 or 5, reactions of which with alkyl halides, aldehydes, and acetone (6,9,10,11) are diastereoselective (lk-1,3-induction). Cleavage of the corresponding products furnishes the enantiomerically pure 2-deuterio-, 2-methyl-, 2-allyl-, and 2-benzyl-substituted 4-hydroxyprolines 2a–2d.