Novel aminoalkylation reactions of electron-rich aromatic compounds
thesisposted on 2017-05-18, 11:37 authored by Robert F. Wilkins
It has been shown that preformed methyleneiminium salts react readily with N-substituted pyrroles, and both furan and 2-methylfuran, to give Mannich bases in good yields. Furan itself has previously been reported not to undergo the Mannich reaction. Thus furan reacts with N,N-dimethy(methylene)iminium chloride to give 2-(N,N-dimethylaminomethyl)furan. Modification of these experimental methods has enabled Mannich reactions to be carried out in non-protic solvents whilst avoiding high concentrations of acid. Thus bis-(dialkylamino)methanes (aminals) and alkoxydialkyl-aminomethanes (aminol ethers) were interacted with sulphur dioxide or chlorosilanes to generate reactive aminoalkylating species "in situ". Such species were then used to functionalise aromatic substrates. It has been demonstrated that a number of cyclic aminals and aminol ethers will function as Mannich reagents in "in situ" reactions. This type of reaction enables two functional groups to be simultaneously introduced into nucleophilic substrates. Thus 2-methylfuran will react with 1,3-dimethylimidazolidine in the presence of trichloromethylsilane to give N,N'-dimethyl-N-(5'-methyl-2'-furylmethyl)ethylene diamine which contains both secondary and tertiary amine groups. Similarly interaction of N-methylindole with 3-methyl-I,3-oxazolidine and a chlorosilane yields 3-(N'-2'-hydroxyethyl-N'-methylaminomethyl)-N -methylindole, which has a tertiary amine substituent and a terminal alcohol functionality. The use of t-butylchlorodimethylsilane as the activating agent enables the said hydroxyl group to be simultaneously protected as its t-butyl-dimethylsilylether. 5-methyl-2-(N-methylaminomethyl)furan was prepared by the removal of the hydroxyethyl substituent from 2-(N-2'-hydroxyethyl-N-methylaminomethyl)- 5-methylfuran. The use of thionyl chloride as an activating reagent has enabled us to prepare methyl 2-(5'-methyl-2'-furyl)-2-(N -2"-chloroethyl-N -methylamino)-acetate, a racemic aryl glycine derivative, from 2-methoxycarbonyl-3-methyl- 1,3-oxazolidine, in a reaction with 2-methylfuran
Publisher© Robert F. Wilkins
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NotesA Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.