N o-alkylation

Particulate organic matter is transitoiy pool between fresh plant residues and humified organic matter (Gregorich and Janzen 1996). Often the term light fraction is used as a synonym for POM (von Lutzow et al. 2007). While POM and LF are similar, they are not equivalent fraction and have different C-, N-, O-alkyl contents (Gregorich et al. 2006). 

Another variation of the Madelung synthesis involves use of an O-alkyl or O-silyl imidate as the C2 electrophile. The mechanistic advantage of this modification stems from avoiding competing N-deprotonation, which presumably reduces the electrophilicity of the amide group under the classical conditions. Examples of this approach to date appear to have been limited to reactants with a EW substituent at the o-alkyl group[15,16]. 

If the oximino intermediates are O-alkylated and then reduced with BHj-N(CH3)3, N-alkoxy tryptophans can be obtained[6]. 

Under suitable conditions, O-alkylation rather than N-alkylation takes place, eg, to form 2-methoxy-l-pyrroline [5264-35-7] (40) (74—76). 

Several types of nitrogen substituents occur in known dye stmetures. The most useful are the acid-substituted alkyl N-substituents such as sulfopropyl, which provide desirable solubiUty and adsorption characteristics for practical cyanine and merocyanine sensitizers. Patents in this area are numerous. Other types of substituents include N-aryl groups, heterocycHc substituents, and complexes of dye bases with metal ions (iridium, platinum, zinc, copper, nickel). Heteroatom substituents directly bonded to nitrogen (N—O, N—NR2, N—OR) provide photochemically reactive dyes. 

The methylation of N-methyl derivatives of maleic hydrazide gives in general O-alkylated products. The opposite results are obtained with benzyl halides as alkylating agents. In this case the O-benzyl derivative (71) is formed, which is then further benzylated to the lV,0-dibenzyl derivative (72). When ethyl chloroacetate is used, the direction of alkylation is dependent on pH. At pH above 8, O-alkylation occurs at pH below 8, N-alkylation takes place exclusively in neutral and acidic solutions only IV-alkylated products are formed. 

Unsubstituted 3-alkyl- or 3-aryl-isoxazoles undergo ring cleavage reactions under more vigorous conditions. In these substrates the deprotonation of the H-5 proton is concurrent with fission of the N—O and C(3)—-C(4) bonds, giving a nitrile and an ethynolate anion. The latter is usually hydrolyzed on work-up to a carboxylic acid, but can be trapped at low temperature. As shown by Scheme 33, such reactions could provide useful syntheses of ketenes and /3-lactones (79LA219). 

Oxaziridines substituted in the 2-position with primary or secondary alkyl groups undergo decomposition at room temperature. In the course of some weeks, slow decomposition of undiluted compounds occurs, the pattern of which is analogous to that of acidic or alkaline N—O cleavage (Sections 5.08.3.1.3 and 4), Radical attack on a C—H bond in (109) effects N—O cleavage, probably synchronously (57JA5739). In the example presented here, methyl isobutyl ketone and ammonia were isolated after two hour s heating at 150 °C. 

The respective amide was prepared from 7-substituted 5-oxo-2,3-dihydro-5//-pyrido[l,2,3-de]-l,4-benzoxazine-6-carboxylic acids via acid chlorides with different benzylamines (00M1P3). 6-Carboxamides were N-benzylated, and a side-chain phenolic hydroxy group was O-alkylated. 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l, 2,3-r/e]-1,4-benzoxazine-6-carboxylic acid was obtained from the ethyl ester by alkalic hydrolysis. 

Aromatische O-Alkyl-oxime ergeben in ahnlicher Weise mit Natrium-cyano-trihydrido-borat die entsprechenden 0,N-Dialkyl-hydroxylamine z. B.2 ... 

O-Alkyl-7 und O-Aryl-hydroxylamine8 lassen sich mit Lithiumalanat in die Komponenten spalten bzw. re-duktivumlagern , O-Acyl-10bzw. N-Sulfonyl-hydroxylamine11 imerstenSchritt zum Hydroxylamin und Al-kohol bzw. Sulfonamid reduzieren. 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

Amides are very weak nucleophiles, far too weak to attack alkyl halides, so they must first be converted to their conjugate bases. By this method, unsubstituted amides can be converted to N-substituted, or N-substituted to N,N-disubstituted, amides. Esters of sulfuric or sulfonic acids can also be substrates. Tertiary substrates give elimination. O-Alkylation is at times a side reaction. Both amides and sulfonamides have been alkylated under phase-transfer conditions. Lactams can be alkylated using similar procedures. Ethyl pyroglutamate (5-carboethoxy 2-pyrrolidinone) and related lactams were converted to N-alkyl derivatives via treatment with NaH (short contact time) followed by addition of the halide. 2-Pyrrolidinone derivatives can be alkylated using a similar procedure. Lactams can be reductively alkylated using aldehydes under catalytic hydrogenation... 

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