Alkylation and hydroxyalkylation

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Synthetic procedures involving other types of intermediates can be based on 2-lithiation. An indirect 2-alkylation can be carried out via indol-2-ylborates which can be prepared by addition of 2-lithioindoles to trialkylboranes. 

Treatment of the borates with iodine leads to boron- C2 migration of an alkyl group[9]. This reaction has not been widely applied synthetically but it might be more applicable for introduction of branched alkyl groups than direct alkylation of an indol-2-yllithium intermediate. 

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Indol-2-ylcopper reagents can also be prepared from 2-lithioindoles and they have some potential for the preparation of 2-substituted indoles. 1-Methyl-indol-2-ylcopper can be prepared by reaction of 2-lithio-l-methylindole with CuBr[10]. It reacts with aryl iodides to give 2-aryl-1-methylindoles. Mixed cyanocuprate reagents can be prepared using CuCN[ll], The cyan-ocuprate from 1-methylindole reacts with allyl bromide to give 2-allyl-l-methylindole. 

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The Reimer-Tiemann reaction is not an effective route to formyl-pyrroles or -indoles (see Section 3.05.1.6) and the oxidation of alkyl and hydroxyalkyl derivatives of the heterocycles and the reduction of carboxylic acid derivatives are discussed in Sections 3.05.2.2 and 3.05.2.4, respectively. 

Alkyl and -hydroxyalkyl radicals. Alkyl radicals, prepared in situ, react with pyridine to form mainly 2-alkyl derivatives and this regioselectivity is shown in the radical reactions of alkylmercurial compounds with pyridines (Scheme 51). 

Dichloropyridazine can be successfully alkylated and hydroxyalkylated by free radicals (Scheme 26). 4-t-Butyl-3,6-dichloropyridazine is prepared in high yield <880PP117>, and in a novel radical hydroxyalkylation, hydroxy-t-butyl radicals generated in situ from 2,2-dimethyl-1,3-pro-panediol react to give the 4-hydroxy-t-butyl derivative (76), along with some of the fused dihydro-furopyridazine byproduct the product (76) can be obtained pure in 55-60% yield by recrystallization. In the latter 3,6-dichloropyridazine reaction, trifluoroacetic acid and silver nitrate both catalyse hydrolysis of the dichloropyridazine substrate, but if the acid is omitted, or the quantity... 

Formation of alkyl and hydroxyalkyl hydroperoxides by the ozonolysis of alkenes, in K.H. Becker (ed). Tropospheric Oxidation Mechanisms Air Pollution Research Report, EC, Brussels 1995, in press. 

Formation of alkyl and hydroxyalkyl hydroperoxides on ozonolysis in water and in air,... 

Water-soluble resins Any of several resin types that are produced by polymerization reactions in which the chain growth results from breaking of ring structure or double bonds of the monomers. Examples are alkyl- and hydroxyalkyl cellulose derivatives, carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid, polyacrylamide, polyethylene oxide, and polyethylene-imide. Tracton AA (ed) (2005) Coatings technology handbook. Taylor and Francis Inc., New York. 

Greminger, G. K., Krumel, K. L. (1980). Alkyl and hydroxyalkyl cellulose. In R. L. Davidson (Ed.), Handbook of water-soluble gums and resins (pp. 3.1-3.25). McGraw-Hill. 

Alkylation and hydroxyalkylation of allenic sulfides, 46 -(22) 4-Phenyl-l-butyne, 48 - (23) l-Chloro-5-hexyne, 48 - 24) 3-Buty-noic acid, 49 - (2S) 2,3-Pentadienedioic acid, 50 - (2S) 2-riethyl-2,3--pentadienedioic acid, 51 - (37) 3-Trimethylsilyl-l-heptyne, 52 - 23) 3-Ethynyl-l-hexanol, 53 - (29) 3-Phenyl-3-trimethylsilyl-l-propyne,... 

Doubly deprotonated methyl 3-nitropropanoate (25) is a new reagent which is alkylated and hydroxyalkylated exclusively at the 2-position by alkyl halides and aldehydes respectively (Scheme 39) a double alkylation can also be performed. Elimination of HNOg with DBN, or better with DBU, in THE furnishes the corresponding a-methylenealkanoates. (3-Nitro-ketones also result from the reaction of 1,1-dinitrohalides with ketone enolates. ... 

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