Reductive alkylation of lipase

Candida rugosa lipase was modified via reductive alkylation to increase its hydrophobicity to work better in organic solvents. The free amino group of lysines was alkylated using propionaldehyde with different degrees of modification obtained (49 and 86%). Far-ultraviolet circular dichroism (CD) spectroscopy of the lipase in aqueous solvent showed that such chemical modifications at the enzyme surface caused a loss in secondary and tertiary structure that is attributed to the enzyme unfolding. Using molecular modeling, we propose that in an aqueous environment the loss in protein structure of the modified lipase is owing to disruption of stabilizing salt bridges, particularly of surface lysines. Indeed, molecular modeling and simulation of a salt bridge formed by Lys-75 to Asp-79, in a nonpolar environment, suggests the adoption of a more flexible alkylated lysine that may explain higher lipase activity in organic solvents on alkylation.     

Reductive alkylation ofE. coli L-asparaginase

Alkylasparaginases have been obtained with the far-reaching modification of 1–10 lysine residues per subunit of the enzyme. It has been established that alkylation does not affect the stability of the enzyme, and the change in the pH optimum of the catalytic action is due to the chemical nature of the alkyl substituent.Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR, Riga. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 232–235, March–April, 1980.     

Reductive alkylation of 2-methoxybenzoic acid derivatives

Metal-ammonia reduction followed by in situ alkylation of 2-methoxybenzoic acids often results in substantial loss of the methoxy substituent; reduction of the carboxylate salts or esters, however, suppresses this side reaction and good to excellent yields of desired products are then obtained.     

Reductive alkylation of p-benzoquinone using mixed organoboranes

Mixed organoboranes based on diphenyl- or dimethylalkylboranes transfer the alkyl group in the reductive alkylation of p-benzoquinone to form the alkylhydroquinones in very high yields. The auxiliary groups do not transfer or have a low migratory aptitude. Primary and secondary alkyl groups are transferred with retention of regio- and stereochemistry to the hydroquinone. O-Alkylation is the major product with tertiary and secondary groups with steric bulk in proximity to the site of attachment. The presence of metal salts, such as magnesium, results in reduction to the unsubstituted hydroquinone. This reaction makes the first practical route to alkylhydroquinones via organoboranes.     

Reductive alkylation of proteins using iridium catalyzed transfer hydrogenation

An efficient transition metal catalyzed procedure for the reductive alkylation of proteins has been developed. Imines formed from the condensation of aldehydes (1 mM) with lysine residues and the N-terminus can be reduced efficiently by a [Cp*Ir(4,4'-dimethoxy-2,2'-bipyridine)(H2O)]SO4 catalyst in the presence of formate ions. The reaction proceeds readily at pH 7.4 in aqueous phosphate buffer at temperatures ranging from 22 to 37 degrees C, and reaches high levels of conversion for a number of aromatic aldehydes. UV experiments have confirmed that the catalyst does not bind to protein substrates. The utility of the reaction has been demonstrated through an efficient two-step procedure for the attachment of unfunctionalized poly(ethylene glycol) to protein targets.     

Reductive hydroxyalkylation/alkylation of amines with lactones/esters

We have developed a one-pot method for the direct intermolecular reductive hydroxyalkylation or alkylation of amines using lactones or esters as the hydroxyalkylating/alkylating reagents. The method is based on the in situ amidation of lactones/esters with DIBAL-H-amine complex (for primary amines) or DIBAL-H-amine hydrochloride salt complex (for secondary amines), followed by reduction of the amides with an excess of DIBAL-H. Different from the reduction of Weinreb amides with DIBAL-H where aldehydes are formed, the reduction of the in situ formed Weinreb amides yielded amines. Moreover, this method is not limited to Weinreb amides, instead, it also works for other amides in general. A plausible mechanism is suggested to account for the outcome of the reactions.     

Reductive alkylation of indoles with alkynes and hydrosilanes under indium catalysis

Under Indium catalysis, diverse alkylindoles were successfully prepared with a flexible combination of indoles and alkynes in the presence of hydrosilanes. In addition to the hydrosilane, carbon nucleophiles are also available. This new method generates alkylindoles in yields over 70% with a broad scope of functional group compatibility.     

Electroorganic synthesis. Reductive alkylation of functionalized 1,2-dithiole-3-thiones

Two-electron reduction of some substituted 1,2-dithiole-3-thiones 1 followed by alkylation of the dianionic intermediates leads through electrosynthesis to mixture of Z and E isomers of the corresponding substituted alkyl-(3-thioalkyl)-2-propenedithioates 2, 3 in satisfactory yield. The structure of those products was established by ¹³C and ¹H nmr and mass spectroscopy. The isomers ratios were determined by nmr spectroscopy.     

Reductive alkylation of anhydrides and lactones: direct access to monosubstituted lactones

Reductive alkylation of anhydrides (1 equiv) with a 2:0.25 mixture of Grignard reagent and Zn(BH₄)₂ afforded monosubstituted lactones in moderate yields. The same sequence applied to unsubstituted lactones gave monoalkylated diols, which were further selectively oxidised with tetra-n-propylammonium perruthenate (TPAP) into the expected monoalkylated lactones.     

Reductive alkylation of beta-alkoxy aziridines: new route to substituted allylic amines

[reaction: see text] A new route to substituted cyclic allylic amines via the reductive alkylation of beta-alkoxy aziridines using excess alkyllithium reagents is described.     

Reductive electrophilic C–H alkylation of quinolines by a reusable iridium nanocatalyst

The incorporation of a coupling step into the reduction of unsaturated systems offers a desirable way for diverse synthesis of functional molecules, but it remains to date a challenge due to the difficulty in controlling the chemoselectivity. Herein, by developing a new heterogeneous iridium catalyst composed of Ir-species (Ir^δ+) and N-doped SiO₂/TiO₂ support (Ir/N-SiO₂/TiO₂), we describe its application in reductive electrophilic mono and dialkylations of quinolines with various 2- or 4-functionalized aryl carbonyls or benzyl alcohols by utilizing renewable formic acid as the reductant. This catalytic transformation offers a practical platform for direct access to a vast range of alkyl THQs, proceeding with excellent step and atom-efficiency, good substrate scope and functional group tolerance, a reusable catalyst and abundantly available feedstocks, and generation of water and carbon dioxide as by-products. The work opens a door to further develop more useful organic transformations under heterogeneous reductive catalysis.

By developing a heterogeneous iridium catalyst composed of a N-doped SiO₂/TiO₂ support and Ir-species (Ir/N-SiO₂/TiO₂), its application in reductive electrophilic alkylation of quinolines with various aryl carbonyls or benzyl alcohols is presented.     

Reductive alkylation of p-phenylenediamine and its hydroquinone complex with ketones in presence of rhenium and palladium sulfides

Conclusions Conditions were found (150–200°, hydrogen pressure 110–150 atm, reaction time 3 h) for the reductive alkylation of p-phenylenediamine and its hydroquinone complex with acetone, butanone, and cyclohexanone in presence of Re₂S₇ or PdS as catalyst, and N,N'-diisopropyl-, N,N'-di-s-butyl-, and N,N'-dicyclohexyl-p-phenylenediamines and their hydroquinone complexes were obtained in 60–90% yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1601–1605, July, 1968.     

Reductive activation of arenes: XIX. Mechanism and some synthetic applications of the alkylation of phthalodinitrile radical anion

Using cyclopropylmethyl bromide as mechanism-sensitive reagent, it was shown that the reaction of phthalonitrile radical anion with alkyl halides in liquid ammonia involves electron transfer. The effects of the nature of alkyl bromide and counterion in the radical anion salt and reaction conditions on the ratio of 2-alkyl-benzonitrile, 4-alkylphthalonitrile, and 2,5-dialkylbenzonitrile were studied. Phthalodinitrile radical anion was found to undergo dimerization with formation of biphenyl-2,3′,4′-tricarbonitrile. The examined transformations may underlie syntheses of phthalonitriles modified at the 4-position.     

对氨基苯酚生产新工艺

以对硝基苯酚为原料，铁粉作还原剂一步反应生产对氨基苯酚．采取对母液除硫和减少水用量及降低结晶温度等方法，使产品得率从40％提高到65％以上，产品的各项指标均达到规定标准，获得较好的经济效益。     

Theoretical studies on electrochemistry of p-aminophenol

Geometric parameters, vibrational frequencies and thermochemical values of p-quinonimine (p-Q) and p-aminophenol (p-AP) were computed by ab initio calculation (HF) and density function theory (DFT) with the 6-31G(d,p) basis set. Cyclic voltammetry with a goldren electrode of p-AP solutions in phosphate buffers at pH 7.30 showed that standard electrode potential of half reaction for (p-Q) and (p-AP) is 0.728V. Standard electrode potential of half reaction for p-Q and p-AP were calculated using the sum of electronic and thermal free energies of p-Q and p-AP with normal hydrogen electrode (NHE) as a reference electrode. The results show that the theoretical standard electrode potential of half reaction for p-Q and p-AP is 0.682V at B3LYP/6-31G(d,p) level and 0.622V at HF/6-31G(d,p) level, respectively, indicating that computed standard electrode potential at B3LYP/6-31G(d,p) level are more reliable than that at HF/6-31G(d,p) level.     

Selective spectrophotometric determination of p-aminophenol and acetaminophen

A specific spectrophotometric method was developed for the determination of p-aminophenol and acetaminophen. The method is based on the reaction of p-aminophenol at ambient temperature with sodium sulphide in presence of an oxidant to produce a methylene blue-like dye. Different oxidizing agents were tried, e.g. Ce(IV) and Fe(III). The colour developed within 10 min and remained stable for at least 3 h. The method was applied successfully to the determination of p-aminophenol in the presence of acetaminophen without prior separation. The method was also applied to the analysis of various commercially available acetaminophen dosage forms and excellent recoveries were obtained comparable to those obtained by official procedures. The reaction product was isolated and a possible reaction mechanism was suggested.