Regiochemical observations on the lithiation of 1,2,4-trichlorobenzene and reaction with DMF and oxamide electrophiles in THF

Tetrahedron Letters

Volumn 44, Issue 30, 2003, Pages 5653-5656

  Burton, Andrew J ^a   Cardwell, Kevin S ^a   Fuchter, Matthew J ^a   Lindvall, Mika K ^a   Patel, Rajnikant ^a   Packham, Terry W ^a   Prodger, Jeremy C ^a   Schilling, Mark B ^a   Walker, Matthew D ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

1,2,4 trichlorobenzene; 2,3,5 trichlorobenzaldehyde; Organolithium; keto amide

Indexed keywords

1,2,4 TRICHLOROBENZENE; AMIDE; GW 356194; N,N DIMETHYLFORMAMIDE; SODIUM CHANNEL BLOCKING AGENT;

ARTICLE; CHEMICAL REACTION; CHEMISTRY; LITHIATION; OBSERVATION;

EID: 0037928455     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)01360-1     Document Type: Article

References (9)

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4. 13C NMR and mass spectral analyses.
5. Deuterated trichlorobenzene, for the synthesis of 7-D / D, was obtained from the corresponding Grignard reagent, suggesting that these reagents do not display the same anion equilibration.
6. 7 Using their predictions, the 2,3,5-isomer should be the next most stable anion after the 2,3,6-isomer. This is supported by our observations.
7. Schlosser M., Marzi E., Cottet F., Büker H.H., Nibberling N.M.M. Chem. Eur. J. 7:2001;3511.
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9. All low energy conformers for all starting materials, adduct anions and product isomers were located using Low Mode Conformational Searching and the MMFF force field in the gas phase, as implemented in MacroModel v. 7.0 (Schrodinger, Inc.). The resulting conformers were further optimised at the B3LYP/6-31+G* level using Gaussian98 A.7 (Gaussian, Inc., Pittsburgh, PA, 1998), and the energies of the adduct anions in THF (using gas phase geometries) were calculated using Tomasi's PCM solvation model. The lowest energy conformer of each isomer was considered in energy comparisons between isomers.