8088 J . Org. Chem., Vol. 64, No. 22, 1999
Griffiths et al.
ca. 75 area %). Purification by distillation gave imidate 18
(190.8 g, GC content 98.7 area %, bp 34 °C/20 mbar). 1H NMR
(CDCl3) δ 6.95 (1 H, s), 3.70 (3 H, s), 2.24 (2 H, m), 1.54 (2 H,
m), 1.36 (2 H, m), 0.93 (3 H, t, J ) 7.5 Hz); HRMS calcd for
C6H12NO (M+ - H) 114.0919, found 114.0918.
of concd H2SO4 and addition of toluene (500 mL). MeOH and
water were removed by vacuum distillation, and the resulting
orange suspension was cooled to 0 °C, treated with POCl3
(214.7 g, 1.40 mol), stirred for 1 h at room temperature, and
heated to 80 °C before addition of DMF (102.9 g, 1.40 mol) (T
rose to 102 °C, HCl evolution). The black reaction mixture was
heated for 2 h at 100 °C, cooled to 40 °C, and poured into water
(350 mL) (exothermic reaction) with maintenance of the
temperature at <30 °C. The reaction flask was washed with
water (50 mL) and EtOAc (300 mL), and to the combined
reaction mixture and wash liquors was added Celite (20.0 g).
The mixture was stirred for 0.25 h at 25 °C before adjustment
of the pH from -0.9 to +1.2 by addition of 30% NaOH (295.6
mL) and removal of the Celite by filtration. The layers were
separated, and the organic phase was washed twice with water
and evaporated to dryness at 65 °C. The residue was diluted
with toluene (151 mL), and the mixture was heated to 60 °C
and cooled slowly to -10 °C. The precipitate was filtered,
washed with cold toluene, and dried to give 2 (51.9 g, HPLC
content 98.6% based on comparison with a standard of known
content, 54.8% yield based on 20). 1H NMR (CDCl3) δ 12.44 (1
H, br s), 9.65 (1 H, s), 2.87 (2 H, t, J ) 7.5 Hz), 1.79 (2 H, m),
1.39 (2 H, m), 0.93 (3 H, t, J ) 7.5 Hz); 13C NMR (CDCl3) δ
177.7 (d), 155.3 (s), 142.0 (s), 126.0 (s), 29.9 (t), 28.5 (t), 22.3
2-Bu tyl-2-im id a zolin -5-on e (11). To a solution of NaOH
(4.04 g, 101 mmol) in MeOH (32 mL) at 0 °C was added
hydrochloride 20 (12.68 g, 101 mmol) in one portion whereupon
the temperature sank to -11 °C. The white suspension was
stirred for 15 min before addition of a solution of imidate 18
(11.74 g, 102 mmol) in toluene (18 mL). The mixture was
stirred for 3 h at room temperature before adjustment of the
pH from 9.9 to 7.0 by addition of a few drops of concd HCl.
The mixture was filtered to remove NaCl, and the filtrate was
concentrated at 20 °C and dried under vacuum before addition
of CH2Cl2 (100 mL). The mixture was filtered to remove ca.
0.6 g of undissolved solid material (residual NaCl and traces
of dimer 25), and the filtrate was concentrated at 20 °C and
dried under high vacuum to give 11 as a yellow solid (14.22 g,
1
estimated purity by H NMR 90-95%, 90-95% yield).
The analytical data from a small sample prepared in 30%
yield by the method used by J acquier9 for the preparation of
imidazolinones 12a and 12b were as follows: mp 79.5-80.5
1
°C H NMR (DMSO-d6) δ 10.8 (1 H, br s), 3.91 (2 H, s), 2.33 (2
H, m), 1.57 (2 H, m), 1.32 (2 H, m), 0.88 (3 H, t, J ) 7.4 Hz);
13C NMR (DMSO-d6) δ 183.4 (s), 164.9 (s), 58.5 (t), 29.3 (t),
27.1 (t), 21.6 (t), 13.5 (q); IR (KBr) 1737, 1619 cm-1; Anal. Calcd
for C7H12N2O: C, 59.98; H, 8.63; N 19.98. Found: C, 58.4; H,
8.4; N, 20.0; HRMS calcd for C7H12N2O 140.0950, found
140.0948.
(t), 13.6 (q); IR (KBr) 1673, 1515 cm-1; HRMS calcd for C8H11
ClN2O 186.0560, found 186.0563.
-
(Z)-2-Bu tyl-4-(dim eth ylam in om eth ylen e)-2-im idazolin -
5-on e (26). To a solution of imidazolinone 11 (20.0 g, 143
mmol) in CH2Cl2 (300 mL) at 20 °C was added acetal 29 (27.72
g, purity ca. 92%, ca. 214 mmol) over 8 min whereupon the
temperature rose to 27 °C. The clear red solution was stirred
for 0.5 h, washed twice with water, dried (MgSO4), filtered,
and evaporated to dryness to give a brown solid (21.96 g).
Recrystallization (with active charcoal treatment) from EtOAc
gave 26 (12.32 g, 44%) as a pale brown solid, mp 115.5-117.5
°C; 1H NMR (CDCl3) δ 10.4 (1 H, br s), 7.07 (1 H, s), 3.55 (3 H,
br s), 3.18 (3 H, br s), 2.50 (2 H, m), 1.66 (2 H, m), 1.40 (2 H,
m), 0.93 (3 H, t, J ) 7.3 Hz); 13C NMR (CDCl3) δ 172.6 (s),
150.7 (s), 141.3 (d), 115.1 (s), 46.2 (q), 39.5 (q), 29.5 (t), 28.9
(t), 22.4 (t), 13.8 (q); IR (KBr) 2929, 1683, 1605 cm-1. Anal.
Calcd for C10H17N3O: C, 61.51; H, 8.78; N, 21.52. Found: C,
61.66; H, 8.77; N, 21.39.
2-Bu tyl-5-ch lor o-1H-im id a zole (27). To a solution of
POCl3 (300 g, 1.92 mol) in chlorobenzene (70 mL) at 95 °C was
added imidazolinone 11 (50.0 g, 0.36 mol) as a solid in one
portion, whereupon the temperature rose to 103 °C. The red-
black mixture was heated for 2 h at 100 °C and cooled to 80
°C before removal of POCl3 and chlorobenzene (total 305.1 g)
by vacuum distillation. The black, oily residue was added to a
mixture of ice (500 g) and EtOAc (100 mL), and the pH was
adjusted to 7 by addition of 30% NaOH (153 mL). The phases
were separated, and the aqueous phase was extracted with
EtOAc. The combined organic layers were dried (MgSO4),
filtered, and concentrated at 30 °C to give a residue (25.54 g)
which was purified by chromatography on silica gel (elution
with EtOAc/hexane 1:1) to give 27 (17.6 g, 31%), mp 62-64
°C; 1H NMR (CDCl3) δ 11.1 (1 H, br s), 6.85 (1 H, s), 2.72 (2 H,
t, J ) 7.5 Hz), 1.69 (2 H, m), 1.35 (2 H, m), 0.89 (3 H, t, J )
7.5 Hz); 13C NMR (CDCl3) δ 148.2 (s), 127.2 (s), 111.6 (d), 30.5
(t), 28.3 (t), 22.3 (t), 13.7 (q); IR (KBr) 1579, 1442 cm-l. Anal.
Calcd for C7H11ClN2: C, 53.00; H, 6.99; N, 17.66. Found: C,
53.50; H, 7.00; N, 17.40.
Meth yl (1-Meth oxyp en tylid en ea m in o)a ceta te (21). To
a suspension of imidate hydrochloride 6 (106.2 g, 0.70 mol) in
CH2Cl2 (1000 mL) at ca. 2 °C was added hydrochloride 20 (88.8
g, 0.71 mol) as a solid in three portions. The mixture was
stirred at 6 h at ca. 0 °C and for 15 h at 22 °C before addition
of a solution of triethylamine (71.2 g, 0.70 mol), whereupon
the temperature rose to 28 °C. The mixture was stirred at 22
°C for 1 h before addition of pH 7 phosphate buffer (700 mL).
The phases were separated, and the aqueous phase was
extracted twice with CH2Cl2. The combined organic layers were
dried (MgSO4), filtered, and concentrated at 20 °C/400 mbar
to give a yellowish oil (111.3 g) which was distilled in vacuo
to give 21 (56.6 g, 43.2%) as a colorless oil (99.1 GC area %,
1
bp 49 °C/1 mbar). H NMR (CDCl3) δ 4.08 (2 H, s), 3.73 (3 H,
s), 3.66 (3 H, s), 2.22 (2 H, m), 1.53 (2 H, m), 1.33 (2 H, m),
0.91 (3 H, t, J ) 7.4 Hz); IR (neat) 1753, 1677 cm-1; HRMS
calcd for C9H17NO3 187.1208, found 187.1211.
Meth yl (2-Bu tyl-5-oxo-2-im id a zolin -l-yl)a ceta te (22). To
a solution of NaOH (0.24 g, 6 mmol) in MeOH (11 mL) at 0 °C
was added hydrochloride 20 (0.76 g, 6 mmol) in one portion.
The white suspension was stirred for 15 min at 0 °C before
addition of a solution of 21 (0.96 g, 5 mmol) in MeOH (5 mL).
The mixture was stirred for 1 h at room temperature (GC
analysis showed no 21), concentrated under vacuum, and
treated with CH2Cl2 (15 mL) and water (15 mL). The layers
were separated, and the aqueous phase was extracted twice
with CH2Cl2. The combined organic layers were dried (MgSO4),
filtered, concentrated, and dried under high vacuum to give
22 as a viscous liquid (0.69 g, 97.5 GC area %) which later
solidified. Attempts to carry out further purification of 22 led
to decomposition, possibly due to a dimerization process
analogous to that undergone by 11 (see above). 1H NMR
(CDCl3) δ 4.26 (2 H, s), 4.15 (2 H, m), 3.78 (3H, s), 2.36 (2 H,
m), 1.72 (2 H, m), 1.43 (2 H, m), 0.95 (3 H, t, J ) 7.4 Hz); 13C
NMR (CDCl3) δ 181.0 (s), 168.1 (s), 164.8 (s), 58.1 (t), 52.8 (q),
41.1 (t), 28.5 (t), 26.8 (t), 22.3 (t), 13.7 (q); HRMS calcd for
(E)-Meth yl P en t-3-en im id a te (37). A solution of (E)-3-
pentenenitrile (35) (90.1 g, purity ca. 90%, 1.0 mol) in MeOH
(64.0 g, 2.0 mol) was cooled to 5 °C before bubbling in gaseous
HCl (75.0 g, 2.06 mmol) over 2 h at such a rate that the
temperature did not exceed 10 °C. The mixture was stirred
for a further 2 h at ca. 7 °C before addition to a mixture of
Et2O (166 mL) and water (300 mL) at 8-16 °C; 30% NaOH
(203.5 mL) was added simultaneously to maintain a pH of ca.
12. The phases were separated, and the organic layer was dried
(MgSO4), filtered, and evaporated in vacuo to give an orange
liquid containing 37 (70 GC area %). Attempted distillation
through a 20 cm Vigreux column at ca. 300 mbar led to some
decomposition but gave two fractions (total 43.4 g) containing
C
10H16N2O3 212.1161, found 212.1162.
2-Bu tyl-5-ch lor o-3H-im id a zole-4-ca r ba ld eh yd e (2). To
a solution of NaOH (20.20 g, 0.50 mol) in MeOH (160 mL) at
0 °C was added hydrochloride 20 (63.42 g, 0.50 mol) in one
portion whereupon the temperature sank to -10 °C. The white
suspension was stirred for 15 min before addition of a solution
of imidate 18 (57.6 g, 0.50 mol) in toluene (101 mL). The
mixture was stirred for 3 h at room temperature before
adjustment of the pH from 8.7 to 7.0 by addition of a few drops