Bella et al.
acetate afforded 3b as pale yellow crystals (1.0 g, 82%); mp:
82-84 °C, 1H NMR δ 2.31 (3H, s, CH3), 3.72 (3H, s, CH3), 3.79
(3H, s, CH3), 4.26 (2H, s, CH2), 5.06 (2H, s, CH2), 6.13 (1H, s,
ArH), 6.93 (1H, s, ArH), 7.22-7.28 (10H, m, ArH), 7.91 (1H,
br, s, NH); 13C NMR δ 13.7 (CH3), 48.4 (CH2), 55.9 (CH3), 57.8
(CH3), 76.2 (CH2), 96.2 (CH), 109.6 (C), 114.6 (CH), 127.4,
127.7, 128.2, 128.6, 128.8, 128.9 (10 × CH), 138.6 (C), 139.7
(C), 140.0 (C), 143.6 (C), 151.5 (C), 157.7 (CdN); IR (Nujol)
1-[2-(Ben zylam in o)ph en yl]eth an on e O-tr ityloxim e 11a.
To a stirred solution containing (2-acetyl-phenyl)benzylam-
monium chloride 2a (1.0 g, 4.4 mmol) in warm ethanol (10 mL),
was added portionwise O-tritylhydroxylamine (1.8 g, 6.5
mmol). After complete addition the mixture was heated at 60
°C and stirred for 10 min before adding a drop of sulfuric acid.
When a white solid separated from solution, the temperature
was lowered to room temperature and the solution stirred for
20 min. The reaction mixture was filtered and the solid cake
was extensively washed with ethanol and dried under vacuum,
to give white crystals of 11a (1.8 g 84%); mp: 160-162 °C; 1H
NMR δ 2.54 (3H, s, CH3), 3.93 (2H, 2 × s, CH2), 6.35 (1H, d,
ArH), 6.57 (1H, t, ArH), 6.96-7.01 (1H, m, ArH), 7.17-7.42
(21H, m, ArH)), 7.49 (1H, br s; NH); 13C NMR δ 13.8 (CH3),
46.5 (CH2), 91.2 (C-O), 111.1 (CH), 114.7 (CH), 117.8 (C),
126.4, 126.6, 127.1, 127.4, 127.7, 128.2, 128.9, 129.3, 129.7,
(22 × CH), 139.7 (C), 143.0 (C), 144.7 (C), 146.7 (C), 157.1 (Cd
N); IR (Nujol) νmax: 3305 (NH), 1603 (CdN), cm-1; LRMS (ES)
m/z 483 [(M + H)+, (16)], 243 (100), HRMS calcd for C34H31N2O
(M+H)+ 483.2436, found 483.2444. The reaction was also
carried out in refluxing ethanol for 10 h, the solvent was
evaporated under reduced pressure and the slurry residue
made basic by a 6M NaOH and extracted with DCM (3 × 20
mL). The combined organic layers were dried with MgSO4,
filtered and the solvent evaporated to give a pale yellow oil.
Separation of the products was performed by column chroma-
tography (alumina), eluting with 10% ethyl acetate in hexane
to give products deriving from thermal cleavage of 3a , i.e.,
trans-1-[2-(benzylamino) phenyl] ethanone oxime (major iso-
ν
max: 3284 (NH), 1624 (CdN) cm-1; EIMS m/z, 390 (M)+, (100)],
300 (55), 283 (87), 268 (14), 205 (7), 193 (12), 178 (15), 91 (60),
77 (6). HRMS calcd for C24H26N2O3 (M+) 390.1943, found
390.1930. Anal. Calcd for C24H26N2O3: C, 73.82; H, 6.71, N,
7.17. Found: C, 73.75, H, 6.74, N, 7.14.
N -Be n zyl-N -{2-[N -(b e n zyloxy)e t h a n im id oyl]-4,5-d i-
m eth oxyp h en yl}-1-m eth yl-2,5-cycloh exa d ien e-1-ca r box-
a m id e 5b. 1-Methylcyclohexa-2,5-diene-1-carbonyl chloride
(0.5 g, 3.2 mmol) was dissolved in dry dichloromethane (5 mL)
and added dropwise to a mixture of 3b (0.8 g, 2.0 mmol) and
a catalytic amount of DMAP in dry distilled pyridine (20 mL).
The resultant mixture was refluxed overnight before adding
HCl (6M, 50 mL). The aqueous layer was extracted with DCM
(2 × 100 mL), the combined organic layer was washed with
water containing a little NaHCO3 (20 mL), water (20 mL) and
dried over MgSO4. The solvent was evaporated at reduced
pressure to give a yellow oil, which was purified by column
chromatography, eluting with ethyl acetate in hexane (1:9f3:
7) in order to furnish amide 5b as a pale yellow oil (0.7 g, 87%);
1H NMR δ 1.25 (3H, s, CH3), 1.95-2.35 (2H, m, CH2), 2.19
(3H, s, CH3), 3.47 (3H, s, CH3), 3.69 and 5.51 (2H, AX, J )
14.0 Hz, CH2), 3.87 (3H, s, CH3), 4.84-5.71 (4H, m, CH), 5.23
(2H, s, CH2), 6.10 (1H, s, ArH), 6.75 (1H, s ArH) 7.09-7.41
(10H, m, ArH)); 13C NMR δ 15.6 (CH3) 26.1 (CH2), 30.0 (CH3),
46.4 (C), 55.2 (CH2), 55.8 (CH3), 56.5 (CH3), 76.6 (CH2), 111.4
(CH), 115.4 (CH), 119.3 (CH), 123.7 (2 × CH), 127.0 (C), 127.4-
129.8, (9 × CH), 132.58 (2 × CH), 133.2 (C), 137.8 (C), 137.9
(C), 147.6 (C), 148.0 (C), 153.8 (CdN), 174.5 (CdO); IR (Nujol)
1
mer) as pale yellow crystals: mp 52-54 °C; H NMR δ 2.33
(3H, s, CH3), 4.40 (2H, m, CH2), 6.62-6.70 (2H, m, ArH), 7.12-
7.41 (7H, ArH), 7.79 (1H, br s, NH); 13C NMR δ 12.5 (CH3),
47.5 (CH2), 111.3 (CH), 115.4 (CH), 117.9 (C), 126.9, 127.1,
128.5, 129.0, 129.9 (CH), 139.4 (C), 146.8 (C), 158.9 (CdN);
IR (Nujol) νmax 3337 (NH), 1604 (CdN), cm-1; EIMS m/z 240
[(M)+, 45), 223(100), HRMS (EI) calcd for C15H16N2O (M+)
240.1262, found 240.1269. cis-1-[2-(Benzylamino) phenyl]-
ethanone oxime as white crystals: 1H NMR δ 2.41 (3H, s, CH3),
4.21(2H, s, CH2), 7.05-7.64 (9H, m, ArH), 8.26 (1H, br s, NH);
13C NMR δ 13.9 (CH3), 47.0 (CH2), 109.3 (CH), 119.0, 121.9,
122.2, 126.1, 127.8, 128.9 (8 × CH), 135.5 (C), 135.7 (C), 142.5
(C), 151.8 (CdN). Triphenylmethane: 13C NMR δ 56.8 (CH),
126.2, 128.2, 129.4 (15 × CH), 143.8 (3 × C).
ν
max: 1638 (CdO), 1518 (CdC), 1260 (CdC), cm-1 CIMS m/z
511 ((M+H)+, 100); HRMS (CI) calcd for C32H35N2O4 (M + H)+
511.2597, found 511.2607. Anal. Calcd for C32H34N2O4: C,
75.27; H, 6.71, N, 5.49. Found: C, 74.75, H, 6.73, N, 6.35.
1-Ben zyl-3-[(ben zyloxy)a m in o]-5,6-d im eth oxy-3-m eth -
yl-1,3-d ih yd r o-2H-in d ol-2-on e 10b. To a stirred refluxing
solution of amide 5b (0.1 g, 0.25 mmol) in benzene (5 mL) was
added 0.5 mL of a solution prepared by dissolving dilauroyl
peroxide (0.12 g, 0.3 mmol) in benzene (2.5 mL). After refluxing
for 5 min methyl thioglycolate (0.05 mL) was added. The
remaining dilauroyl peroxide solution was then added over 8
h. After complete addition, the solution was refluxed for 30 h,
the solvent was evaporated at reduced pressure and the
product was analyzed by GC-MS; peak tR 3.6 min; methyl
thioglycolate, peak tR 10.3 min; undecane (from initiator), peak
tR 16.1 min; disulfide (dimer of thiol), peak tR 17.1 min; lauric
acid (from initiator), peak tR 23.5 min; docosane (from initia-
tor), peak tR 28.2 min; 10b. The total reaction product was
dissolved in DCM (20 mL) and treated with a warm 6M
solution of KOH (50 mL). The aqueous phase was extracted
with DCM (3 × 25 mL) and the combined organic layers dried
with magnesium sulfate and evaporated at reduced pressure
to leave a brown solid which was purified by column chroma-
tography eluting with a mixture 40% ethyl acetate in hexane
N-Ben zyl-1-m et h yl-N-[2-[N-(t r it yloxy)et h a n im id oyl]-
p h en yl]-2,5-cycloh exa d ien e-1-ca r b oxa m id e 12a . To a
stirred mixture containing 11a (1.4 g, 2.9 mmol) and a catalytic
amount of DMAP in dry distilled pyridine (20 mL) was slowly
added a solution prepared by dissolving 1-methylcyclohexa-
2,5-diene-1-carbonyl chloride (0.67 g, 4.4 mmol) in dry DCM
(5 mL). The resultant mixture was refluxed overnight before
pouring into aqueous HCl (6 M, 50 mL). The aqueous layer
was extracted with DCM (2 × 100 mL), and the combined
organic layers were washed with water containing a little
NaHCO3 (20 mL) and water (20 mL), and dried over MgSO4.
The solvent was evaporated at reduced pressure to leave a
reddish oil, which was purified by column chromatography,
eluting with ethyl acetate 5% in hexane (Rf ) 0.27) in order
to furnish 12a as a white solid which was crystallized from a
mixture ethyl acetate/hexane/DCM affording colorless crystals
(1.43 g, 82%): mp 164-166 °C; 1H NMR δH 1.19 (3H, s, CH3),
1.85-2.23 (2H, AB, CH2), 2.42 (3H, s, CH3), 3.40 and 5.51 (2H,
AX, J gem ) 14.3 Hz, CH2), 4.72-5.64 (4H, m, dCH), 6.53 (1H,
d, ArH), 6.78-7.37 (23H, m, ArH); 13C NMR δ 16.4 (CH3) 25.6
(CH2), 29.8 (CH3), 45.8 (C), 54.4 (CH2), 91.0 (C), 120.1 (CH),
123.1 (2 × CH), 126.8, 127.0, 127.2, 127.6, 127.8, 129.2, 129.6
129.0, (23 × CH), 131.8 (2 × CH), 135.1 (C), 137.5 (C), 138.9
(C), 144.7 (3 × C), 154.4 (CdN), 173.9 (CdO); IR (Nujol) νmax
1632 (CdO), cm-1; ESMS m/z 625 [(M + Na)+, 100); HRMS
(ES) calcd for C42H38N2O2Na (M + Na)+ 625.2831, found
625.2823. Anal. Calcd for C42H38N2O2: C, 83.69; H, 6.35, N,
4.65. Found: C, 83.75, H, 6.49, N, 4.45.
1
(Rf ) 0.28) to give 10b as a yellow pale oil (0.05 g, 63%); H
NMR δ 1.37 (3H, s, CH3), 3.74 (3H, s, CH3), 3.84 (3H, s, CH3),
4.40 and 4.50 (2H, AB, J ) 11.0 Hz, CH2), 4.70 and 5.13 (2H,
AB, J ) 15.9 Hz, CH2), 6.26 (1H, s, NH), 6.93-6.99 (1H, m,
ArH), 7.10-7.26 (11H, m, ArH), 13C NMR δ 19.9 (CH3) 43.6
(CH2), 56.0 (CH3), 56.5 (CH3) 65.6 (C), 76.4 (CH2), 95.3 (CH),
108.1 (CH), 120.8 (C), 126.6, 127.1, 127.4, 127.9, 128.2, 128.4,
(10 × CH), 135.2 (C), 136.5 (C), 136.8 (C), 144.9 (C), 149.6 (C)
178.7 (CdO); IR (neat) νmax: 3235 (NH), 1718 (CdO) cm-1
;
EIMS m/z 358 (M+, 15), 327 (20), 236 (53), 91 (100); HRMS
(EI) calcd for C25H26N2O4 418.1893, found 418.1885.
5932 J . Org. Chem., Vol. 69, No. 18, 2004