New synthetic reactions, involving the use of solids

Doctoral thesis English OPEN
Shalabi, Ahmed Fekri Abdel
  • Subject: QD

Directed lithiation and substitution of various N-benzyl pivalamides and various N'-benzyl-N,N-dimethylureas could be achieved using f-BuLi in THF at low temperature followed by reactions with various electrophiles to give ring substitution ortho to the pivaloylaminomethyl side-chain and urea containing group respectively. Trifluoroacetic anhydride induced dehydration of substituted 2-(pivaloylaminomethyl)phenyl- and 2 (dimethylaminocarbonylmethyl)phenylmethanols gives the corresponding isoindolines in excellent yields. Lithiation of 2- and 4-substituted pyridines, namely N-(pyridinylmethyl)pivalamides, N'-(pyridinylmethyl)-N,N-dimethylureas and pyridinylmethyl tert-butylcarbamates, with two mole equivalents of f-BuLi in anhydrous THF at -78 C takes place on the nitrogen and on the methylene group of the side-chain. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding side-chain substituted derivatives in high yields. While the lithiation and substitution of N-(pyridin-3-ylmethyl)pivalamide, N'-(pyridin-3-ylmethyl)-N,N-dimethylurea and pyridin-3- ylmethyl tert-butylcarbamate with two mole equivalents of alkyllithium in anhydrous THF at -78 C takes place on the nitrogen and on the ortho-position or on the side-chain depending on the type of lithium reagent. Treatment of one of the ring substituted products with trifluoroacetic anhydride in dichloromethane under reflux conditions led to formation of the corresponding 1 H-pyrrolo 3,4-c pyridine. A convenient method for Knoevenagel condensation of aromatic aldehydes with active methylene compounds to synthesize arylidene compounds was developed using inexpensive and environmentally friendly reagents such as K2C03. The method is simple and the conditions are mild to provide high product yields. A boron reaction, which produces an alkyl ester via migration without any by-product, has been developed using HBCI2 on a solid-support.
  • References (5)

    2.4.3 Syntheses of A/-(2-substituted 4- 40 chlorobenzyl)pivalamides 2.20-2.25 via directed lithiation of A/-(4-chlorobenzyl)pivalamide (2.6)

    2.4.4 Syntheses of 2.26-2.33 via directed lithiation of A/-(4- 46 fluorobenzyl)pivalamide (2.15) and A/-(4- trifluoromethylbenzyl)pivalamide (2.16)

    2.4.5 Syn th eses of A/'-(4-substituted benzyl)-N,N- 53 dimethylureas 2.36, 2.38 and 2.39

    2.4.6 S yn th eses of 2.40-2.47 via directed lithiation of A/-(4- 56 fluorobenzyl)-A/,A/-dimethylurea (2.36), A/-(4- chlorobenzyl)-A/,/V-dimethylurea (2.38) and A/-(4-trifluoromethylbenzyl)-A/,A/-dimethylurea (2.39)

    R eferences 64

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