Synthesis of Juvenile Hormone Bioanalogs
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(NH); 4.12 q, 2 H, J = 7.1 (OCH2CH3); 4.01 t, 2 H, J = 5.1 (2 × H-2); 3.57 br q, 2 H, J = 5.4 (2 ×
H-1); 3.48 m, 1 H (H-2″); 2.66 dd, 1 H, J = 8.3 and 13.6 (1 H of C6H4CH2); 2.51 dd, 1 H, J = 7.1
and 13.6 (1 H of C6H4CH2); 1.74–1.20 m, 1 H (H-1″, H-3″, 2 × H-4″, 2 × H-5″, 2 × H-6″); 1.24 t,
3 H, J = 7.1 (OCH2CH3); 0.92 d, 3 H, J = 6.8 (Me-3″). Mass spectrum (m/z, %): 335 (3, M+), 176
(6), 116 (100), 107 (30), 88 (47). For C19H29NO4 (335.4) calculated: 68.03% C, 8.71% H, 4.18% N;
found: 68.05% C, 8.80% H, 4.20% N. Yield 0.20 g (10%) of 15. IR spectrum: 3 640, 3 465, 1 727,
1 612, 1 509, 1 446. 1H NMR spectrum: 7.09 m, 2 H (2 × arom. H); 6.80 m, 2 H (2 × arom. H);
5.16 br t, 1 H, J = 5.4 (NH); 4.12 q, 2 H, J = 7.1 (OCH2CH3); 4.00 t, 2 H, J = 5.1 (H-2); 3.57 br q,
2 H, J = 5.1 (H-1); 3.10 dd, 1 H, J = 3.9 and 13.6 (1 H of C6H4CH2); 2.84 t, 1 H, J = 9.8 (H-2″);
2.32 dd, 1 H, J = 8.9 and 13.6 (1 H of C6H4CH2); 1.74–0.86 m, 8 H (H-1″, H-3″, 2 × H-4″, 2 × H-5″,
2 × H-6″); 1.24 t, 3 H, J = 7.1 (OCH2CH3); 1.02 d, 3 H, J = 6.4 (Me-3″). Mass spectrum (m/z, %):
335 (5, M+), 176 (6), 116 (100), 88 (44). For C19H29NO4 (335.4) calculated: 68.03% C, 8.71% H,
4.18% N; found: 68.00% C, 8.72% H, 4.19% N.
cis-2-(4-Methoxymethoxybenzyl)-6-methylcyclohexanone (16)
A solution of the isomeric mixture 11 (14.1 g, 64.7 mmol) in dry benzene (142 ml) was added to a
stirred suspension of sodium hydride (3.5 g, 72.8 mmol) in dry benzene (100 ml) under nitrogen and
the mixture was refluxed for 1 h. The mixture was cooled to 0 °C, chloromethyl methyl ether (15.7 g,
194.1 mmol) was added, and the mixture was stirred for 9 h at 0 °C. Water (50 ml) was added and
the mixture was extracted with ether (3 × 100 ml), washed with a 5% aqueous solution of NaOH (50 ml),
with water (2 × 100 ml), and the organic layer was dried (MgSO4). The volatiles were evaporated in
vacuo, and the crude 16 was separated from its respective trans-isomer by CC (light petroleum–ether
1
5 : 1) to yield pure 16 (8.20 g, 49%). IR spectrum: 1 713, 1 612, 1 511, 1 154, 1 081, 1 012. H NMR
spectrum: 7.07 m, 2 H (2 × arom. H); 6.94 m, 2 H (2 × arom. H); 5.14 s, 2 H (OCH2); 3.47 s, 3 H
(OMe); 3.16 dd, 1 H, J = 5.1 and 14.0 (1 H of C6H4CH2); 2.50 m, 1 H (H-2); 2.41 m, 1 H (H-6);
2.34 dd, 1 H, J = 8.2 and 14.0 (1 H of C6H4CH2); 2.12–1.26 m, 6 H (2 × H-3, 2 × H-4, 2 × H-5);
1.02 d, 3 H, J = 5.9 (Me-6). Mass spectrum (m/z, %): 262 (32, M+), 151 (49), 121 (34), 91 (5), 77
(5), 45 (100). For C16H22O3 (262.3) calculated: 73.24% C, 8.45% H; found: 73.31% C, 8.40% H.
2-c-(4-Methoxymethoxybenzyl)-6-c-methyl-1-r-cyclohexanol (17) and 2-t-(4-Methoxymethoxy-
benzyl)-6-t-methyl-1-r-cyclohexanol (18)
Ketone 16 (7.0 g, 26.6 mmol) was reduced by the same procedure as the reduction of ketone 5 to
yield a mixture of isomeric alcohols 17 and 18 (HPLC 17/18 1.23 : 1) that were separated by CC
(light petroleum–ether 3 : 1). Yield of pure 17 3.48 g, (49%). IR spectrum: 3 638, 1 612, 1 511, 1 153,
1
1 080, 1 013. H NMR spectrum: 7.10 m, 2 H (2 × arom. H); 6.96 m, 2 H (2 × arom. H); 5.15 s, 2 H
(OCH2); 3.49 br t, 1 H, J = 2.4 (H-1); 3.48 s, 3 H (OMe); 2.66 dd, 1 H, J = 8.2 and 13.5 (1 H of
C6H4CH2); 2.52 dd, 1 H, J = 7.0 and 13.5 (1 H of C6H4CH2); 1.71–1.20 m, 8 H (H-2, 2 × H-3, 2 × H-4,
2 × H-5, H-6); 0.92 d, 3 H, J = 6.7 (Me-6). Mass spectrum (m/z, %): 264 (26, M+), 246 (14), 151
(18), 121 (22), 45 (100). For C16H24O3 (264.4) calculated: 72.69% C, 9.15% H; found: 72.60% C,
1
9.11% H. Yield 3.12 g, (44%) of 18. IR spectrum: 3 638, 1 612, 1 446, 1 153, 1 080, 1 013. H NMR
spectrum: 7.09 m, 2 H (2 × arom. H); 6.95 m, 2 H (2 × arom. H); 5.15 s, 2 H (OCH2); 3.48 s, 3 H
(OMe); 3.11 dd, 1 H, J = 3.9 and 13.5 (1 H of C6H4CH2); 2.85 t, 1 H, J = 9.7 (H-1); 2.31 dd, 1 H,
J = 9.0 and 13.5 (1 H of C6H4CH2); 1.69–1.32 m, 8 H (H-2, 2 × H-3, 2 × H-4, 2 × H-5, H-6); 1.02 d,
3 H, J = 6.8 (Me-6). Mass spectrum (m/z, %): 264 (20, M+), 246 (10), 151 (15), 121 (21), 45 (100).
For C16H24O3 (264.4) calculated: 72.69% C, 9.15% H; found: 72.61% C, 9.21% H.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)