C. Bozzo et al. / Tetrahedron 59 (2003) 1227–1236
1235
C-7); 142.6 (C-8a); 143.1 (C-4a); 164.4 (CO). MS (EI), m/z
(%): 247 (26); 219 (6); 163 (10); 138 (30); 112 (75); 84 (50);
69 (100). Anal. Calcd for C14H17NO3: C, 67.99%; H,
6.93%; N, 5.66%. Found: C, 68.34%; H, 6.65%; N, 5.48%.
H-40 and H-60); 8.86 (bs, OH). 13H NMR (75.5 MHz,
CDCl3), d (ppm), 12.4 (CH3); 14.3 (CH3); 39.8 (CH2); 43.5
(CH2); 96.1 (C-3); 117.9 (C-30); 119.3 (C-50); 122.2 (C-60);
126.4 (C-40); 143.1 (C-10); 148.9 (C-20); 154.5 (C-2); 165.5
(CO). MS (CI, CH4), m/z (%): 292 (10); 264 (14); 236 (100).
Anal. Calcd for C13H17NO3: C, 66.36%; H, 7.28%; N,
5.96%. Found: C, 66.64%; H, 7.15%; N, 5.58%.
2-(2-Hydroxyphenoxy)-N,N-pentamethylen-3-piperidino-
propanamide (18). IR (NaCl) y (cm21), 3460, 1635, 1266,
1
1196. H NMR (500 MHz, CDCl3), d (ppm), 1.50 (m, 4H,
C30H2 and C40H2);1.63 (m, 2H, C400H2); 1.70 (m, 4H,
C300(C500)H2; 2.50 (dd, J¼14, 1.5 Hz, 1H, CH–N); 2.61 (bs,
2H, C200and C600Hax); 2.69 (bs, 2H, C200 and C600Heq); 3.00
(dd, J¼14, 11 Hz, 1H, CH-N); 3.39 (m, 1H, C60Hax); 3.52
(m, 2H, C20Hax, C60Heq); 3.62 (m, 1H, C20Heq); 4.58 (d,
J¼11 Hz, 1H, CH2-O); 6.68 (ddd, J¼8.0, 7.2, 1.5 Hz, 1H,
H-5); 6.90 (dd, J¼8.5, 2.0 Hz, 1H, H-3); 6.97 (m, 2H, H-4
and H-6). 13C NMR (50.3 MHz, CDCl3), d (ppm), 23.3
(C-200); 24.1 (C-4000); 24.9 (C-300 and C-500); 25.4 (C-30); 26.2
(C-5 ); 43.2 (C-6 ); 55.1 (C-200 and C-600); 60.9 (CH2); 80.6
(CH); 117.2 (C-3) and 118.5 (C-5); 122.1 (C-6); 125.5
(C-4); 145.9 (C-1); 150.5 (C-2); 167.5 (CO). MS (EI), m/z
(%): 332 (5); 223 (43); 138 (19); 98 (100). Anal. Calcd for
C19H28N2O3: C, 68.65%; H, 8.49%; N, 8.43%. Found: C,
68.30%; H, 8.57%; N, 8.47%.
2-(2-Hydroxyphenoxy)-N,N-diethyl-3-(N0,N0-diethylamino)-
propanamide (23). IR (NaCl) y (cm21), 3465, 1646, 1258,
1108. 1H NMR (200 MHz, CDCl3), d (ppm), 1.22 (m, 12H,
CH3); 3.10 (dd, J¼14.0, 11.0 Hz, 1H, CH-N); 3.47. (q,
J¼7.0 Hz, 4H, CH2); 3.65 (m, 4H, CH2); 4.65 (d, J¼3.0 Hz,
1H, CH); 4.69 (d, J¼3.0 Hz, 1H, CH); 6.84 (dd, J¼8.0,
7.0 Hz 1H, H-50);0 7.10 (d, J¼9.0 Hz, 1H, H-30); 7.12 (m,
2H, H-40 and H-6 ); 8.90 (bs, OH). 13C NMR (50.3 MHz,
CDCl3), d (ppm), 12.2 (CH3); 14.5 (CH3); 40.2 (CH2); 43.5
(CH2); 59.8 (CH2); 82.3 (CH); 116.9 and 117.8 (C-3 and
C-5); 122.8 (C-6); 126.5 (C-4); 145.6 (C-1); 151.2 (C-2);
166.3 (CO). Anal. Calcd for C17H27N2O3: C, 66.42%; H,
8.85%; N, 9.11%. Found: C, 66.23%; H, 8.50%; N, 9.49%.
3.3.3. trans N,N-Diethylamine-3-diethylamino-2,3-di-
hydro-1,4-benzodioxin-2-carboxa-mide (24). To a stirred
solution of the amide 2 (215 mg, 0.92 mmol) in dry toluene
(15 mL), was added diethylamine (1.90 mL, 18.30 mmol).
The reaction mixture was heated at reflux for 24 h. Then was
cooled and diethylamine (1.90 mL, 18.30 mmol) was added.
The resulting mixture was stirred at reflux for 24 h. Then
the crude of reaction was cooled to room temperature,
the solvent was removed and directly passed through a
chromatography column on silica gel (hexane/ethyl acetate
(6/4)) to give the trans aminoamide 24 (272 mg, 96% yield).
IR (KBr) y (cm21), 1622, 1498, 1258, 1100. 1H NMR
(300 MHz, CDCl3), d (ppm), 1.08 (t, J¼7.1 Hz, 6H, CH3);
1.18 (t, J¼7.1 Hz, 3H, CH3); 1.26 (t, J¼7.1 Hz, 3H, CH3);
2.75–2.94 (m, 4H, CH2N); 4.65 (d, J¼7.7 Hz, 1H, H-2);
5.12 (d, J¼7.7 Hz, 1H, H-3); 6.75–6.97 (m, 4H, H-arom).
13H NMR (75.5 MHz, CDCl3), d (ppm), 12.6 (CH3); 13.8
(CH3); 14.8 (CH3); 40.7 (CH2); 41.9 (CH2); 43.2 (CH2);
70.3 (C-2); 88.4 (C-3); 116.7 and 117.0 (C-5 and C-8);
120.5 and 121.8 (C-6 and C-7); 142.1 and 143.8 (C-4a and
C-8a); 166.0 (CO). MS (EI), m/z (%): 306 (6); 233 (45); 218
(21); 190 (12). Anal. Calcd for C17H26N2O3: C, 66.64%; H,
8.55%; N, 9.14%. Found: C, 66.87%; H, 8.78%; N, 9.46%.
3.3.2. N,N-Diethyl-2,3-dihydro-1,4-benzodioxin-2-carb-
oxamide (19). This compound was prepared according to
the above procedure starting from the ester 16 (550 mg,
2.64 mmol). The reaction mixture was purified by column
chromatography (hexane/ethyl acetate (80/20)) to give the
amide 19 (326 mg, 1.39 mmol, 52% yield) as a pale yellow
oil. Eluting with hexane/ethyl acetate (70/30) gave the
phenol 21 (27 mg, 4% yield) as a white solid with mp¼93–
958C. Eluting with hexane/ethyl acetate (50/50) give only
trace of the lactone 20. Finally, with ethyl acetate 100%
only trace of the aminophenol 23 was obtained. Amide 19.
IR (NaCl) y (cm21), 1650, 1250, 1095. 1H NMR (500 MHz,
CDCl3), d (ppm), 1.16 (t, J¼7.1 Hz, 3H, CH3); 1.27 (t, J¼
7.1 Hz, 3H, CH3); 3.40 (m, 2H, CH2–); 3.48 (m, 2H, CH2–);
4.29 (dd, J¼12, 8.5 Hz, 1H, C3Hax); 4.45 (dd, J¼12.0,
2.5 Hz, 1H, C3Heq); 4.47 (dd, J¼8.5, 2.5 Hz, 1H, H-2); 6.86
(m, 4H, H-arom). 13C NMR (75.5 MHz, CDCl3), d (ppm),
12.6 (CH3); 14.5 (CH3); 40.2 (CH2); 41.8 (CH2); 65.5 (C-3);
70.7 (C-2); 117.18 and 117.24 (C-5 and C-8); 121.3 and
121.9 (C-6 and C-7); 142.8 and 143.2 (C-4a and C-8a);
165.5 (CO). MS (CI, CH4), m/z (%): 276 (10); 264 (29); 236
(100). Anal. Calcd for C13H17NO3: C, 66.364%; H, 7.28%;
N, 5.96%. Found: C, 66.26%; H, 7.56%; N, 5.87%.
Acknowledgements
3-Methylene-2,3-dihydro-1,4-benzodioxin-2(3H)-one (20).
The compound 20 was obtained as a by-product in the
preparation of the amide 19. IR (KBr) y (cm21), 3112, 1643,
Financial support of this work was provided by the
Generalitat de Catalunya (2001-SGR-00085) and the
´
Ministerio de Educacion y Cultura (SPAIN) (CYCIT
QUI1999-0512).
1
1242, 1100. H NMR (300 MHz, CDCl3), d (ppm), 4.46
(d, J¼3.2 Hz, 1H, CH); 5.52 (d0, J¼3.1 Hz, 1H, CH); 6.81
(ddd, J¼0 8, 7.1, 1.8 Hz, 1H, H-5 ); 7.001 (dd, J¼8.5, 1.8 Hz,
1H, H-3 ); 7.07 (m, 2H, H-40 and H-6 ).
N,N-Diethyl-2-(2-hydroxyphenoxy)acrylamide (21). IR
1
References
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1H, H-5 ); 7.01 (dd, J¼8.5, 1.8 Hz, 1H, H-3 ); 7.07 (m, 2H,
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