Acid-Catalyzed Z/E Isomerization of Imines
J . Org. Chem., Vol. 66, No. 24, 2001 7985
81% 1Zi and 19% 1Ei. A sample of 1Zi was obtained by
for C10H10NCl: C, 61.39; H, 5.15; N, 7.16; Cl, 18.12. Found:
C, 61.13; H, 5.14; N, 7.19; Cl, 18.20.
1
preparative GC. H NMR (90 MHz) (δ): 3.95 (s, 3H), 4.72 (q,
2H, J ) 8 Hz), 7.40 (m, 3H), 7.80 (m, 2H). IR (neat, cm-1):
1622, 1614, 1576. Anal. Calcd for C10H9NO2F3: C, 51.51; H,
4.32; N, 6.01; F, 24.44. Found: C, 51.31; H, 4.31; N, 5.95; F,
24.24.
Meth yl (Z,E)-O-Meth ylcin n a m oh yd r oxim a te (2Zb).36
Sodium metal (3.85 g) was dissolved in methanol (70 mL) in a
250 mL round-bottomed flask fitted with a condenser, and a
dropping funnel. A solution of (Z,E)-O-methylcinnamohydroxi-
moyl chloride (5.58 g) in dimethyl sulfoxide (100 mL) was
added through the dropping funnel with stirring. The mixture
was stirred and heated at 50 °C for 24 h. The flask was allowed
to cool to room temperature and then poured into ice-cold
water (300 mL). The mixture was extracted with ether, and
the ether extracts were dried over anhydrous magnesium
sulfate. The ether was removed by rotary evaporation under
aspirator pressure to give a yellow oil. The oil was microdis-
tilled to yield 2ZB as a light yellow liquid (2.8 g, 51%). Bp:
2,2,2-Tr iflu or oeth yl (E)-O-Meth ylben zoh yd r oxim a te
(1Ei). A glacial acetic acid (15 mL) solution of 1Zi and 1Ei
(1.00 g) obtained from the previous procedure was heated at
80 °C for 3.5 h. The solution was poured into 6 N sodium
hydroxide solution (50 mL), and the resulting mixture was
extracted with ether. The ether extracts were dried over
magnesium sulfate and evaporated to give a clear oil. GC
analysis of the oil showed that it was a mixture of 1Zi and
1Ei in a ratio of 57:43. The E isomer (1Ei) was obtained by
1
1
80-84 °C/0.05 mmHg. H NMR (300 MHz) (δ): 3.89 (s, 3H),
preparative GC. H NMR (δ): 3.83 (s, 3H), 4.52 (q, 2H, J ) 8
Hz), 7.45 (m, 3H), 7.85 (m, 2H). IR (neat, cm-1): 1633, 1603,
1578. Anal. Calcd for C10H9NO2F3: C, 51.51; H, 4.32; N, 6.01;
F, 24.44. Found: C, 51.65; H, 4.41; N, 5.87; F, 24.28.
3.99 (s, 3H), 6.45-6.50 (d, J ) 16 Hz, 1H), 7.10-7.15 (d, J )
16 Hz, 1H), 7.30-7.46 (m, 5H). 13C NMR (75 MHz) (δ): 59.30,
62.25, 117.75, 126.87, 127.97, 134.90, 135.46, 155.77. IR (neat,
cm-1): 1627.9. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85;
N, 7.32. Found: C, 69.18; H, 6.83; N, 7.38.
(Z,E)-O-Met h ylcin n a m oh yd r oxim oyl Ch lor id e (2Za ).
This compound was recently reported,35 but it was isolated only
as a crude product. Methyl cinnamohydroxamate35 (18.01 g)
in carbon tetrachloride (25 mL) was placed in a 250 mL round-
bottomed flask fitted with a condenser and a solid addition
funnel. Phosphorus pentachloride (21.17 g) was added slowly,
with stirring, through the addition funnel. With continued
addition of phosphorus pentachloride, the solution progres-
sively turned to a vivid yellow color. The temperature of the
solution was maintained between 37 and 43 °C. After the
addition of the phosphorus pentachloride, the solution was
heated to 68 °C and this temperature was maintained for 6 h.
The resulting liquid was allowed to cool to room temperature
and was then slowly poured into ice-cold water. The mixture
was extracted with ether. The ether extracts were then
extracted with saturated sodium bicarbonate solution and
dried with anhydrous magnesium sulfate. The solvent was
removed by rotary evaporation under aspirator pressure to
yield a yellow semisolid. The crude product was distilled to
give an amber-colored liquid (12.71 g, 64%). Bp: 90-93 °C/
Meth yl (E,E)-O-Meth ylcin n a m oh yd r oxim a te (2Eb).36
A
solution of methyl (Z,E)-O-methylcinnamohydroximate (2.80
g) and glacial acetic acid (100 mL) was heated at 80 °C for 4
h. The reaction mixture was quenched with 6 M NaOH (400
mL) at the end of the reaction period. The resulting solution
was extracted with ether. The ether extracts were dried over
anhydrous magnesium sulfate, and the ether was evaporated
under aspirator pressure. The resulting oil was analyzed by
GC-MS and found to contain 2Zb and 2Eb in a ratio of 45:
55. The E-hydroximate 2Eb was separated by column chro-
matography using a mixture of hexane and chloroform in a
ratio of 2:1. The oil was further purified by distillation. Bp:
1
73-74/0.1 mmHg. H NMR (300 MHz) (δ): 3.79 (s, 3H), 3.83
(s, 3H), 7.10-7.05 (d, J ) 16 Hz, 1H), 7.24-7.19 (d, J ) 16
Hz, 1H), 7.32-7.52 (m, 5H). 13C (75 MHz) (δ): 54.08, 61.82,
111.60, 127.37, 128.46, 128.89 135.63 136.13 159.20. IR (neat,
cm-1) 1638.05. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85;
N, 7.32. Found: C, 68.94; H, 6.87; N, 7.49.
1
0.05 mmHg. H NMR (300 MHz) (δ): 4.04 (s, 3H), 6.81-6.87
Ack n ow led gm en t is made to the Minority Biomedi-
cal Research Support Program of the National Institutes
of Health (NIH-MBRS Grant GM08256), The Robert A.
Welch Foundation, and the Texas Woman’s University
Research Enhancement Program for support of this
work.
(d, J ) 16 Hz, 1H,), 7.28-7.23 (d, J ) 16 Hz, 1H), 7.34-7.48
(m, 5H); 13C NMR (75 MHz) (δ): 62.99, 120.40, 127.08, 128.61,
128.93, 135.02, 137.11, 137.96; IR (neat, cm-1) 1631.2; Anal.
Calcd for C10H10NCl: C, 61.39; H, 5.15; N, 7.16; Cl, 18.12.
Found: C, 61.60; H, 5.18; N, 7.24; Cl, 17.94.
(E,E)-O-Meth ylcin n a m oh yd r oxim oyl Ch lor id e (2Ea ).
A solution of (Z,E)-O-methylcinnamohydroximoyl chloride
(4.03 g) in hexane (84 mL) was placed in six quartz tubes. The
test tubes were irradiated in a Rayonet photochemical reactor
(254 nm) for 6 h. Immediately after irradiation, the hexane
solution was extracted with a saturated solution of sodium
carbonate. The hexane extracts were dried over anhydrous
magnesium sulfate, and the hexane was removed in a rotary
evaporator at aspirator pressure. Analysis of the resulting oil
by GC-MS showed that the oil contained 2Za and 2Ea in a
ratio of 35:65. The hydroximoyl chloride 2Ea 36 was separated
by column chromatography using a solution of hexane and
chloroform in a ratio of 10:2. The oil was further purified by
Su p p or tin g In for m a tion Ava ila ble: Tables giving the
Cartesian coordinates for 1ZjH+, 1EjH+, 1Zk H+, 1Ek H+,
2ZcH+, 2EcH+, 2Zd H+, 2Ed H+, 1Za H+, 1Ea H+, 1ZbH+,
1EbH+, 2Za H+, and 2Ea H+ at the HF6-31+G(*) + ZPVE level
of theory and experimental procedures including spectral data
(1H and 13C NMR and infrared spectra) for 1Zd -h and 1Ed -h
are provided. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O010067K
(36) The isomer produced by ultraviolet irratdiation of 2Za was
determined to be the result of isomerization about the carbon-nitrogen
double bond (rather than isomerization about the carbon-carbon
double bond) from its 1H NMR spectrum; i.e., the CHdCH coupling
constant in both 2Za and 2Eb is 16 Hz which is consistent with a trans
configuration at the carbon-carbon double bond (see ref 37). Similarily,
the configurations of 2Zb and 2Eb at the carbon-carbon double bond
are trans (J ) 16 Hz).
1
distillation. Bp: 33-34/0.05 mmHg. H NMR (300 MHz) (δ):
4.00 (s, 3H), 7.25-7.30 (d, J ) 16 Hz, 1H), 7.33-7.54 (m, 6H).
13C NMR (75 MHz) (δ): 62.97, 113.82, 127.81, 128.64, 129.68,
134.79, 139.0.86, 147.60. IR (neat, cm-1): 1619.81. Anal. Calcd
(35) Miyata, O.; Nishiguchi, A.; Ninomiya, I.; Aoe, K.; Okamura, K.;
Naito, T. J . Org. Chem. 2000, 65, 6922-6931.
(37) Friebolin, H. Basic One- and Two-Dimensional NMR Spectros-
copy; VCH: New York, 1991; pp 77-82.