Alkylation in basic media

V-Hydroxy groups can be acetylated (AC2O) and O-alkylated in basic media by methyl iodide. 1-Hydroxypyrazole 2-oxides are quite strong acids. 

Most aldehyde-based chiral auxiliaries come from carbohydrates [248]. For example, aldehyde 1.97 is transformed into a-aminoester imines 1.98, which undergo stereoselective alkylations in basic media. After acidic hydrolysis, the dural... 

Pyrazole alkylation in basic media [122] A very important microwave-specific effect was apparent in the absence of a base in the reaction of pyrazole with phenethyl bromide (reaction times MW = 8 min, A = 48 h, Eq. 69). When the same reaction was performed in the presence of KOH, the microwave effect disappeared vide supra Eq. 46). 

Azolinones are protonated on oxygen in strongly acidic media. O-Alkylation of 2-azolinones can be effected with diazomethane thiazolinone (486) forms (487). Frequently O- and iV-alkylation occur together, especially in basic media where proton loss gives an ambident anion. 

It has been noted that imidazolium ions are not inert. Under mild basic conditions, they are deprotonated to give reaetive nucleophiles. For reactions in basic media, the C2 hydrogen of the imidazolium ring can be replaced with an alkyl group. In one study, the C2 hydrogen was substituted by a methyl group. Ionie liquids based on the C2 methylated imidazolium cation were evaluated for the... 

The alkylation of thiurets (297) in basic media affords 3-thio-5-imino-l,2,4-thiadiazolidines (305)... 

Despite the highly selective alkylations of azaenolates, the optical purity of the final products is rather low in several cases, due to partial racemization during hydrolysis of the alkylated imines. In general, racemization occurs very fast in basic media, whereas in acidic solutions, especially in two-phase systems, the degree of racemization is rather low and depends on the nature of the carbonyl compounds. 

Perimidines with a free NH-group (360) in basic media form readily oxidizable anions (361). The latter can be A-alkylated in inert atmosphere, the reaction being sensitive to steric interference from 2-and 4(9)-substituents (81RCR1559). 

Alkylation of A-oxides, e.g., in basic media by methyl iodide, usually takes place at the oxygen (89S773, 90S795, 91CHE802) as does acylation (by e.g. Ac20) (89TL4353, 90S795). 

N-Unsubstituted 1,4-dihydroazines very easily undergo N-alkylation and N-acylation in basic media—KOH [308], NaOH [309], NaOMe [310], LiN(-SiMe3)2 [311], pyridine [312], DMAP [313], etc. [246, 247]. 

Picramide and its N-substituted derivatives introduce the added complication that proton loss may occur from the amino-group to give the Bronsted bases 23 (R = H, alkyl, phenyl). Green and Rowe (1913) found support for this formula from the alkali metal analyses of the solids formed from many polynitroanilines with bases. In fact picramide itself has been frequently used as an indicator for establishing H-acidity scales in basic media on the assumption that its indicator behaviour is due to proton loss (Schaal, 1955 Stewart and O Donnell, 1962 Stewart et al., 1962). The most likely other alternatives for the products of 1 1 interaction of picramides with bases are 24 and 25 (R = H, alkyl, phenyl R =R = H, alkyl). Formula 24, the analogue of Meisenheimer s formula for the adducts of picryl ethers, was suggested by Busch and... 

Conversely, when negatively charged surfactants (e.g., long-chain alkyl phosphates) are used as SDAs, it is possible to work in basic media, whereby again a mediator ion, in this case a positively charged one (M+), must be added to... 

The reaction between an alcohol and the halide of a non-metal (usually phosphorus) is well known in the synthesis of alkyl halides. Usually the reaction is conducted with an excess of alcohol and/or in basic media thus... 

Alkyl substituents in aromatic azoloazines are reactive towards electrophilic reagents in basic media. Basic reagents readily abstract protons from such alkyl groups yielding resonance stabilized carbanions. Thus, treatment of the methyl derivatives (243) with aldehydes gives the alkenes (245) (Scheme 21) <84H(22)174i). Ready formation of the resonance stabilized anions (244) is behind the activity of the methyl group. 

The alkylation of thiurets (347) in basic media produces the imino derivatives (352) possibly via intermediates such as (350) and (351) (Nu = soft nucleophile), as indicated in Scheme 127 (74IJC134). The acid-catalyzed dealkylation of (352 R = (-butyl) results in a reverse isomerization to the thiuret (347). The reaction takes a different course when iV-alkyl thiurets of type (353) are alkylated in the presence of an amine. In this case intermediate (354) is postulated to exchange with the amine to form a guanidine which undergoes ring closure to yield (355 Scheme 128) (74JOC2235). Thermolysis of (356) also produces (355) presumably via a spiran intermediate. 

Whereas free thiol or thione functions are readily alkylated, especially in basic media (62JCS3124), 2-alkylthiouracils normally alkylate preferentially at N-3 (82ACS(B)15). With dimethylformamide dimethylacetal, significant... 

Migrations of the double bond and carbon-skeleton rearrangements are important in the preparation of several olefinic compounds. A number of alkyl cyclopentenes are available in quantities suitable for synthetic work by the isomerization of cyclohexene and its homologs over alumina at 470- 480°. o-Allylphenol is isomerized by methanolic potassium hydroxide at 110° to o-propenylphenol (75%). Several /5, y-olefinic acids are conveniently obtained from the corresponding a /3-isomers by equilibration in basic media. The two isomeric acids are readily separated by partial esterification of the resulting mixtures since the /3,y-isomers are more easily esterified. "... 

As a rule of thumb one ean assume that reactions which are carried out in basic media involve the anion (5), which A -alkylates to give mainly the 1,4 isomer (6) if R is bulky or electron-withdrawing. In free base alkylations the tautomeric mixture (3) (4) reacts. An electron-withdrawing substituent (R) will ensure that much of the reaction will be with the major tautomer (3) even if that tautomer is the less reactive. The product mixture formed will have mainly 1,5 regiochemistry (7), e.g. 4(5)-nitroimidazole methylated in basic medium gives mainly l-methyl-4-nitroimidazole in neutral media l-methyl-5-nitroimidazole forms almost exclusively. Sterically demanding groups, however, favour the 1,4 isomer. Table 7.1.1 lists some other examples. 

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