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DOI: 10.1055/s-0029-1217722
Unexpected Variations in Sites of Lithiation of N-(2-Methoxybenzyl)-pivalamide
Publication History
Publication Date:
03 August 2009 (online)
Abstract
Directed lithiation of N-(2-methoxybenzyl)pivalamide with two mole equivalents of t-BuLi in anhydrous THF at -78 ˚C followed by reactions with various electrophiles gave ring substitution, but ortho to the methoxy group rather than ortho to the pivaloylaminomethyl group, which was unexpected in view of earlier results reported with n-BuLi.
Key words
N-(2-methoxybenzyl)pivalamide - directed lithiation - synthesis - dilithium intermediate - electrophile
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References and Notes
Analytical Data
for Compound 2: Mp 170-171 ˚C (lit.
[6]
168-169 ˚C). ¹H
NMR (500 MHz, DMSO-d
6): δ = 7.43
(t, J = 6
Hz, exch., 1 H, NH), 7.34 (app. t, J = 8
Hz, 1 H, H-5), 7.27 (dd, J = 2,
8 Hz, 1 H, H-6), 7.19 (br d, J = 8
Hz, 1 H, H-4), 4.47 (d, J = 6
Hz, 2 H, CH2), 3.82 (s, 3 H, OCH3), 1.05 [s, 9
H, C(CH3)3] ppm. ¹³C
NMR (125 MHz, DMSO-d
6): δ = 177.5
(s, C=O), 169.7 (s, CO2H), 158.4 (s, C-3), 134.3
(s, C-2), 128.7 (d, C-5), 126.7 (s, C-1), 121.6 (d, C-6), 114.6
(d, C-4), 56.5 (q, OCH3), 38.4 [s, C(CH3)3],
35.7 (t, CH2), 27.8 [q, C(CH3)3] ppm.
MS (ES+): m/z (%) = 553
(34) [2 M + Na]+,
531 (42) [2 M + H]+,
329 (32) [M + MeCNNa]+,
304 (3) [M + K]+,
266 (100) [MH]+. HRMS (ES+): m/z calcd for C14H20NO4 [MH]+:
266.1392; found: 266.1392. FT-IR: νmax = 3401,
2965, 1698, 1611, 1539, 1467, 1385, 1219
cm-¹.
Analytical Data
for Compound 4: Mp 156-157 ˚C. ¹H NMR
(500 MHz, DMSO-d
6): δ = 8.03
(t, J = 6
Hz, exch., 1 H, NH), 7.57 (dd, J = 2,
8 Hz, 1 H, H-6), 7.32 (dd, J = 2,
8 Hz, 1 H, H-4), 7.16 (app. t, J = 8
Hz, 1 H, H-5), 4.32 (d, J = 6 Hz,
2 H, CH2), 3.79 (s, 3 H, OCH3), 1.15 [s,
9 H, C(CH3)3] ppm. ¹³C
NMR (500 MHz, DMSO-d
6): δ = 178.1
(s, C=O), 167.8 (s, CO2H), 157.1 (s, C-2), 134.6
(s, C-3), 131.5 (d,
C-4), 129.6 (d, C-6), 126.1 (s, C-1),
123.9 (d, C-5), 62.1 (q, OCH3), 38.6 [s, C(CH3)3],
37.3 (t, CH2), 27.9 [q, C(CH3)3] ppm.
MS (ES+): m/z (%) = 569
(12) [2 M + K]+,
553 (100) [2 M + Na]+,
548 (32) [2 M + NH4]+,
329 (25) [M + MeCNNa]+,
304 (27) [M + K]+,
288 (70) [M + Na]+,
266 (71) [MH]+. HRMS (ES+): m/z calcd for C14H20NO4 [MH]+: 266.1392;
found: 266.1386. FT-IR: νmax = 3377,
2972, 1698, 1610, 1540, 1427, 1368, 1247 cm-¹.