2196 J . Org. Chem., Vol. 67, No. 7, 2002
Szakonyi et al.
was dissolved in 50 mL of an ethereal solution of CH2N2, and
the solution was strirred for 48 h at room temperature. When
the reaction was complete (checked by H NMR), the solution
2H, CH2CH2CH3), 3.22 (s, 3H, COOCH3), 4.88 (t, 1H, J ) 5.3
Hz, NH), 6.83-7.11 (m, 3H, ArH), 7.86 (d, 1H, J ) 7.9 Hz,
ArH); 13C NMR (C6D6, 67.9 MHz) δ 11.4 (CH2CH2CH3), 23.7
(CH2CH2CH3), 26.6 (cyclopropane CH2), 30.3 (ArCH2), 31.2
(CH), 42.0 (Cq), 42.5 (CH2CH2CH3), 52.1 (COOCH3), 124.3,
127.7, 128.0, 128.4 (CH, aromatic), 134, 7, 141.1 (Cq, aromatic),
155.4 (NCONH), 172.6 (COOCH3); IR (KBr, cm-1) 3359, 2958,
1742, 1652; LRMS (70 eV, m/z) 289 (M + 1+, 10), 203 (100),
176 (53), 143 (49). Anal. Calcd for C16H20N2O3: C, 66.65; H,
6.99; N, 9.72. Found: C, 66.32; H, 7.25; N, 9.49.
1
was evaporated to dryness and the yellow residual oil was
purified by Kugelrohr distillation (110 °C air bath, 0.05
mmHg), which resulted in 0.61 g (62%) of pure compound 14
as a yellow oil: 1H NMR (CDCl3, 500 MHz) δ 1.27 (dd, 1 H, J
) 4.8, 6.7 Hz, cyclopropane CH2), 1.34 (dd, 1 H, J ) 4.6, 9.5
Hz, cyclopropane CH2), 2.15-2.18 (m, 1 H, CH), 2.91 (d, 1 H,
J ) 16.1 Hz, ArCH2), 3.16 (dd, 1 H, J ) 5.5, 16.1 Hz, ArCH2),
3.77 (s, 3 H, COOCH3), 6.62 (d, 1 H, J ) 7.9 Hz, ArH), 6.72 (t,
1 H, J ) 7.3 Hz, ArH), 6.97 (d, 1 H, J ) 7.4 Hz, ArH), 7.02 (t,
1 H, J ) 7.5 Hz, ArH); 13C NMR (CDCl3, 67.9 MHz) δ 18.2
(cyclopropane CH2), 23.2 (CH), 26.4 (ArCH2), 40.2 (Cq), 52.2
(COOCH3), 115.0, 119.5, 127.1, 129.2 (CH, aromatic), 118.9,
2-P h en yl-4a ,5-d ih yd r o-1H ,4H -cyclop r op a [e]im id a zo-
[1,5-a ]qu in olin e-1,3(2H)-d ion e (21a ). A 0.17 g (0.53 mmol)
portion of urea 20a was dissolved in 10 mL of MeOH, and 5
drops of methanol containing 25% of dry NH3 was added to
the solution. The reaction was complete after being stirred for
1.5 h at room temperature (TLC monitoring). The solution was
evaporated to dryness, and the resulting crystalline product
was recrystallized from EtOAc/petroleum ether to yield 0.125
141.5 (Cq, aromatic), 173.6 (COO); IR (liquid film, NaBr, cm-1
)
3392, 2954, 1725, 1441, 909, 734; LRMS (70 eV, m/z) 204 (M
+ 1+, 69), 144 (100). Anal. Calcd for C12H13NO2: C, 70.92; H,
6.45; N, 6.89. Found: C, 70.76; H, 6.59; N, 6.71.
1
g (80%) of 21a : mp 162-163 °C; H NMR (CDCl3, 270 MHz)
Meth yl N-(P h en yla m in oca r bon yl)-1,2,7,7a -tetr a h yd r o-
1aH-cyclopr opa[b]qu in olin e-1a-car boxylate (20a). A 0.172
g (0.9 mmol) portion of amino ester 5 and 0.106 g (0.95 mmol)
of phenyl isocyanate were dissolved in 5 mL of dry toluene,
and the solution was stirred overnight at room temperature.
Evaporation to dryness, followed by chomatographic purifica-
tion on silica gel (eluent: petroleum ether/EtOAc ) 2:1, Rf
0.35), resulted in 0.21 g (72%) of compound 20a : mp 143-
δ 1.58 (t, 1H, J ) 5.9, cyclopropane CH2), 1.67 (dd, 1H, J )
5.9, 9.6 Hz, cyclopropane CH2), 2.42-2.49 (m, 1H, CH), 3.15
(d, 1H, J ) 16.2 Hz, ArCH2), 3.26 (dd, 1H, J ) 4.0, 16.5 Hz,
ArCH2), 7.1-7.5 (m, 8H, ArH), 7.93 (d, 1H, J ) 8.3 Hz, ArH);
13C NMR (CDCl3, 67.9 MHz) δ 15.0 (cyclopropane CH2), 22.3
(CH), 27.1 (ArCH2), 44.5 (Cq), 121.0, 125.1, 126.3, 127.9, 128.2,
129.1, 130.0 (CH, aromatic), 123.9, 131.8, 132.0 (Cq, aromatic),
152.0 (NCON), 171.1 (NCOCq); IR (KBr, cm-1) 3467, 1772,
1722, 1404; LRMS (70 eV, m/z) 290 (M+, 51), 262 (26), 156
(13), 143 (100). Anal. Calcd for C18H14N2O2: C, 74.47; H, 4.86;
N, 9.65. Found: C, 74.52; H, 5.23; N, 9.49.
2-(p-Tolyl)-4a ,5-d ih yd r o-1H,4H-cyclop r op a [e]im id a zo-
[1,5-a ]qu in olin e-1,3(2H)-d ion e (21b). Starting from 0.12 g
(0.36 mmol) of 20b, the procedure used was similar to that
for the preparation of 21a from 20a : yield 78%, mp 143-144
°C; 1H NMR (CDCl3, 270 MHz) δ 1.61 (dd, 1H, J ) 5.9, 9.8
Hz, cyclopropane CH2), 1.69 (dd, 1H, J ) 5.9, 9.6 Hz, cyclo-
propane CH2), 2.40 (s, 3H, ArCH3), 2.43-2.51 (m, 1H, CH),
3.18 (d, 1H, J ) 15.5 Hz, ArCH2), 3.29 (dd, 1H, J ) 4.3, 15.5
Hz, ArCH2), 7.08-7.39 (m, 7H, ArH), 7.93 (d, 1H, J ) 8.3 Hz,
ArH); 13C NMR (CDCl3, 67.9 MHz) δ 15.2 (cyclopropane CH2),
21.4 (CH3), 22.5 (CH), 27.3 (ArCH2), 44.7 (Cq), 121.2, 126.4,
125.3, 128.2, 130.0, 130.3 (CH, aromatic), 124.1, 129.3, 132.3,
138.5 (Cq, aromatic), 152.5 (NCON), 171.5 (NCOCq); IR (KBr,
cm-1) 1773, 1718, 1406, 1146; LRMS (70 eV, m/z) 305 (M+,
24), 144 (100), 116 (21). Anal. Calcd for C19H16N2O2: C, 74.98;
H, 5.30; N, 9.20. Found: C, 74.62; H, 5.59; N, 8.91.
2-P r op yl-4a ,5-d ih yd r o-1H ,4H -cyclop r op a [e]im id a zo-
[1,5-a ]qu in olin e-1,3(2H)-d ion e (21c). Starting from 0.08 g
(0.28 mmol) of 20c, the procedure used was similar to that for
the preparation of 21a from 20a : yield 85%; mp 80-81
°C; 1H NMR (CDCl3, 270 MHz) δ 0.98 (t, 3H, J ) 7.4 Hz,
CH2CH2CH3), 1.42-1.53 (m, 1H, cyclopropane CH2), 1.58 (dd,
1H, J ) 5.9, 9.6 Hz, cyclopropane CH2), 1.61-1.81 (m, 2H,
CH2CH2CH3), 2.33-2.41 (m, 1H, CH), 3.13 (dd, 1H, J ) 1.5,
16.5 Hz, ArCH2), 3.21 (dd, 1H, J ) 4.0, 16.5 Hz, ArCH2), 3.59-
3.65 (m, 2H, CH2CH2CH3), 7.04-7.31 (m, 3H, ArH), 7.89 (d,
1H, J ) 8.3 Hz, ArH); 13C NMR (CDCl3, 67.9 MHz) δ 11.3
(CH2CH2CH3), 14.5 (CH2CH2CH3), 21.6 (cyclopropane CH2),
21.7 (CH2CH2CH3), 27.0 (CH), 40.8 (ArCH2), 44.4 (Cq), 120.8,
124.8, 127.9, 130.0 (CH, aromatic), 123.7, 132.2 (Cq, aromatic),
153.3 (NCON), 172.2 (NCOCq); IR (KBr, cm-1) 2930, 1760,
1710, 1416; LRMS (70 eV, m/z) 256 (M+, 57), 170 (4), 143 (100),
128 (20). Anal. Calcd for C15H16N2O2: C, 70.29; H, 6.29; N,
10.93. Found: C, 70.55; H, 6.62; N, 10.65.
1
146 °C; H NMR (C6D6, 270 MHz) δ 1.04 (t, 1H, J ) 5.8 Hz,
cyclopropane CH2), 1.80 (dd, 1H, J ) 15.2, 6.9 Hz, ArCH2),
1.88-2.0 (m, 1H, CH), 2.1-2.2 (m, 1H, cyclopropane CH2), 2.58
(dd, 1H, J ) 15.0, 7.8 Hz, ArCH2), 3.20 (s, 3H, COOCH3), 6.8-
7.1 (m, 6H, ArH), 7.16 (s, 1H, NH), 7.45 (d, 2H, J ) 7.9 Hz,
ArH), 7.55 (d, 1H, J ) 7.9 Hz, ArH); 13C NMR (C6D6, 67.9 MHz)
δ 27.8 (cyclopropane CH2), 31.3 (ArCH2), 32.1 (CH), 43.4 (Cq),
53.3 (COOCH3), 120.3, 124.3, 125.0, 126.1, 128.6, 129.7, 130.3
(CH, aromatic), 136.4, 140.6, 141.6 (Cq, aromatic), 153.9
(NCONH), 173.4 (COOCH3); IR (KBr, cm-1) 3296, 1728, 1656;
LRMS (70 eV, m/z) 322 (M+, 17), 203 (100), 175 (50), 143 (55).
Anal. Calcd for C19H18N2O3: C, 70.79; H, 5.63; N, 8.69.
Found: C, 70.42; H, 6.01; N, 8.41.
Meth yl N-(p-Tolyla m in oca r bon yl)-1,2,7,7a -tetr a h yd r o-
1aH-cyclopr opa[b]qu in olin e-1a-car boxylate (20b). A 0.255
g (1.33 mmol) portion of amino ester 5 and 0.16 g (1.4 mmol)
of p-tolyl isocyanate were dissolved in 10 mL of dry toluene,
and the solution was stirred overnight at 80 °C. Evaporation
to dryness, followed by chromatographic purification on silica
gel (eluent: petroleum ether/EtOAc ) 2:1, Rf 0.4), resulted in
0.31 g (68%) of compound 20b: mp 103-105 °C; 1H NMR
(C6D6, 270 MHz) δ 1.02 (t, 1H, J ) 5.9 Hz, cyclopropane CH2),
1.78 (dd, 1H, J ) 7.1, 15.3 Hz, ArCH2), 1.90 (m, 1H, CH), 2.06
(s, 3H, ArCH3), 2.17 (dd, 1H, J ) 4.9, 8.6 Hz, cyclopropane
CH2), 2.57 (dd, 1H, J ) 7.8, 15.3 Hz, ArCH2), 3.20 (s, 3H,
COOCH3), 6.83-7.03 (m, 6H, ArH + NH), 7.40 (d, 2H, J )
8.6 Hz, ArH), 7.57 (d, 1H, J ) 7.9 Hz, ArH); 13C NMR (C6D6,
67.9 MHz) δ 20.7 (ArCH3), 26.6 (cyclopropane CH2), 30.2
(ArCH2), 31.0 (CH), 42.3 (Cq), 52.2 (COOCH3), 119.4, 127.7,
128.0, 128.4, 128.6, 129.6 (CH, aromatic), 123.9, 124.9, 132.5,
135.3 (Cq, aromatic), 152.9 (NCONH), 172.4 (COOCH3); IR
(KBr, cm-1) 3414, 1728, 1677, 1520, 1320; LRMS (70 eV, m/z)
337 (M + 1+, 22), 203 (100), 175 (61), 143 (57). Anal. Calcd for
C
20H20N2O3: C, 71.41; H, 5.99; N, 8.33. Found: C, 71.05; H,
6.17; N, 8.56.
Met h yl 2-P r op yla m in oca r b on yl-1,2,7,7a -t et r a h yd r o-
1a H-cyclop r op a [b]qu in olin e-1a -ca r boxyla te (20c). A 0.16
g (0.84 mmol) portion of amino ester 5 and 0.075 g (0.88 mmol)
of propyl isocyanate were dissolved in 5 mL of dry toluene,
and the solution was stirred overnight at 80 °C. Evaporation
to dryness, followed by chromatographic purification on silica
gel (eluent: petroleum ether/EtOAc ) 2:1, Rf 0.28), resulted
in 0.140 g (58%) of compound 20c: mp 103-106 °C; 1H NMR
(C6D6, 270 MHz) δ 0.73 (t, 3H, J ) 7.3 Hz, CH2CH2CH3), 1.04
(t, 1H, J ) 5.9 Hz, cyclopropane CH2), 1.23-1.36 (m, 2H,
CH2CH2CH3), 1.83 (dd, 1H, J ) 6.9, 14.9 Hz, ArCH2), 1.91-
2.02 (m, 1H, CH), 2.11 (dd, 1H, J ) 4.9, 8.6 Hz, cyclopropane
CH2), 2.63 (dd, 1H, J ) 7.9, 15.2 Hz, ArCH2), 3.04-3.7 (m,
Ackn owledgm en t. The authors express their thanks
for the financial support from the Fund for Scientific
Research-Flanders (Belgium) (FWO-Vlaanderen) and
the Flemish-Hungarian Bilateral Research Cooperation
(BWTS). Z.S. is indebted to the National Scientific
Research Foundation, Hungary (OTKA, F 032828) and
the Foundation for Hungarian Research and Higher
Education (AMFK).
J O010993Z