Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives
J . Org. Chem., Vol. 62, No. 3, 1997 667
g), was added using a syringe at the same temperature. The
resulting mixture was allowed to warm up to room tempera-
ture and stirring was continued for an additional 2 h before
20 mL of saturated aqueous NH4Cl was added to quench the
reaction. The organic layer was separated, and the aqueous
layer was extracted with Et2O (3 × 20 mL). The combined
ether layers were washed five times with water and then once
with brine, dried over anhydrous MgSO4, and concentrated
under reduced pressure. The residue was purified by prepara-
tive TLC on SiO2 to afford the title compound 5b as a pale
yellow solid (0.23 g, 98%): Rf 0.46 (1:5 EtOAc-hexane); mp
(1.5H, d, J ) 6.9 Hz), 2.41 (0.5H, qd, J ) 6.9, 2.5 Hz), 2.65-
2.75 (1H, m), 2.90 (0.5H, qd, J ) 15.2, 6.9 Hz), 4.58 (2H, br s),
7.2-7.4 (4H, m); MS (rel intensity) m/ z 198 (M+, 32), 183
(100). Anal. Calcd for C13H14N2: C, 78.75; H, 7.12; N, 14.13.
Found: C, 78.65; H, 6.99; N, 14.30.
1-Am in o-3,4-d ih yd r o-3,7-d im eth yl-2-n a p h th a len eca r -
bon itr ile (5i): Rf 0.25 (1:3 EtOAc-hexane); IR (neat) 3443,
3366, 3254, 2168, 1656 cm-1; 1H NMR (60 MHz, CDCl3) δ 1.17
(3H, d, J ) 6.9 Hz), 2.2-2.95 (6H, m including s at 2.33), 4.70
(2H, br s), 7.0-7.2 (3H, m); MS (rel intensity) m/ z 198 (M+,
29), 183 (100). Anal. Calcd for C13H14N2: C, 78.75; H, 7.12;
N, 14.13. Found: C, 78.57; H, 6.98; N, 14.34.
88-91 °C (hexane); IR (KBr disk) 3448, 3322, 1652, 1616 cm-1
;
1H NMR (270 MHz, CDCl3) δ 0.87 (3H, d, J ) 6.9 Hz), 1.32
(3H, t, J ) 7.3 Hz), 2.56 (1H, d, J ) 13.5 Hz), 3.0-3.15 (2H,
m), 4.15-4.3 (2H, m), 6.50 (2H, br s), 7.15-7.35 (3H, m), 7.44
(1H, dd, J ) 8.9, 2.0 Hz); 13C NMR (67.9 MHz, CDCl3) δ 14.6,
18.7, 26.3, 36.0, 59.0, 99.2, 122.1, 126.5, 129.2, 129.7, 130.6,
138.0, 150.8, 170.3; MS (rel intensity) m/ z 231 (M+, 76), 216
(99), 144 (99), 143 (100). Anal. Calcd for C14H17NO2: C, 72.70;
H, 7.40; N, 6.06. Found: C, 72.46; H, 7.35; N, 6.12.
Following the above-mentioned procedure (method B) the
dihydronaphthalenecarbonitriles 5c-j were prepared. Forma-
tion of the carbonitriles by the ZnI2-promoted enolate-nitrile
coupling was faster than that of the carboxylates, and 1 h
stirring proved to be ample.
Eth yl 1-Am in o-3,4-d ih yd r o-6,7,8-tr im eth oxy-3-m eth yl-
2-n a p h th a len eca r boxyla te (5j): Rf 0.20 (1:3, EtOAc-hex-
ane); IR (neat) 3467, 3307, 1651, 1601 cm-1 1H NMR (270
;
MHz, CDCl3) δ 0.88 (3H, d, J ) 6.9 Hz), 1.31 (3H, t, J ) 7.3
Hz), 2.45 (1H, d, J ) 13.4 Hz), 2.93 (1H, d, J ) 5.4 Hz), 3.03
(1H, dd, 1H, J ) 13.4, 5.4 Hz), 3.86, 3.87, and 3.89 (combined
9H, 3s), 4.15-4.25 (2H, m), 6.54 (1H, s), 8.68 (2H, br s); MS
(rel intensity) m/ z 321 (M+, 17), 306 (100). Anal. Calcd for
C17H23NO5: C, 63.54; H, 7.21; N, 4.36%. Found: C, 63.77; H,
7.36; N, 4.24%.
Eth yl 1-Am in o-3-m eth yl-2-n aph th alen ecar boxylate (6b).
Gen er a l P r oced u r e for Deh yd r ogen a tion of 5. The di-
hydronaphthalenecarboxylate 5b (0.61 mmol, 0.14 g) was
dissolved in dry p-cymene (3 mL), and 10% Pd on activated
carbon (0.061 mmol, 64 mg) was added. The mixture was
heated at reflux temperature for 12 h, the reaction being
followed by TLC or taking small aliquots for analysis by 1H
NMR. After cooling and filtration of the catalyst, concentra-
tion of the filtrate under reduced pressure gave a residue,
which was subjected to preparative TLC on SiO2 to give 6b
(0.13 g, 90%) as a pale yellow oil: Rf 0.41 (1:5, EtOAc-hexane);
IR (neat) 3486, 3366, 1678, 1601 cm-1; 1H NMR (60 MHz, CCl4)
δ 1.40 (3H, t, J ) 7.2 Hz), 2.53 (1H, s), 3.0-3.15 (2H, m), 4.36
(2H, q, J ) 7.2 Hz), 6.16 (2H, br s), 6.84 (1H, s),7.1-7.85 (4H,
m); MS (rel intensity) m/ z 229 (M+, 100). Anal. Calcd for
C14H15NO2: C, 73.34; H, 6.59; N, 6.11. Found: C, 73.11 H,
6.29; N, 5.97.
E t h yl 1-Am in o-3,4-d ih yd r o-3-p h en yl-2-n a p h t h a len e-
ca r boxyla te (5c): Rf 0.37 (1:3 EtOAc-hexane); mp 109-112
1
°C (hexane); IR (KBr disk) 3442, 3318, 1656, 1618 cm-1; H
NMR (270 MHz, CDCl3) δ 1.17 (3H, t, J ) 7.3 Hz), 2.93 (1H,
dd, J ) 15.2, 1.8 Hz), 3.38 (1H, dd, J ) 15.2, 7.3 Hz), 4.0-
4.25 (2H, m), 4.27 (1H, dd, J ) 7.3, 1.8 Hz), 6.73 (2H, br s),
6.95-7.15 (5H, m), 7.2-7.3 (3H, m), 7.44 (1H, dd, J ) 8.7, 1.8
Hz); MS (rel intensity) m/ z 293 (M+, 24), 220 (100). Anal.
Calcd for C19H19NO2: C, 77.79; H, 6.53; N, 4.77. Found: C,
77.81; H, 6.49; N, 4.93.
1-Am in o-3,4-d ih yd r o-3-m eth yl-2-n a p h th a len eca r bon i-
tr ile (5d ): Rf 0.15 (1:10 EtOAc-hexane); mp 108-110 °C
(hexane); IR (KBr disk) 3463, 3363, 3254, 2178, 1636 cm-1
;
1H NMR (270 MHz, CDCl3) δ 1.19 (3H, d, J ) 6.3 Hz), 2.58
(1H, dd, J ) 14.2, 9.0 Hz), 2.6-2.7 (1H, m), 2.90 (1H, dd, J )
14.2, 4.2 Hz), 4.59 (2H, br s), 7.15-7.4 (4H, m); 13C NMR (67.9
MHz, CDCl3) δ 19.4, 27.8, 36.6, 82.1, 120.2, 122.0, 126.9, 128.7,
128.9, 130.2, 137.4, 151.6; MS (rel intensity) m/ z 184 (M+, 16),
169 (100). Anal. Calcd for C12H12N2: C, 78.23; H, 6.56; N,
15.20. Found: C, 78.51; H, 6.64; N, 15.00.
Following the above-mentioned procedure, the aminonaph-
thalenecarboxylic acid derivatives 6a -e and 6g-j were pre-
pared. Heating for 10-12 h was required to complete dehy-
drogenation to the carboxylates. Dehydrogenation to the
carbonitriles was faster than that to the carboxylates and
completed after 5-8 h.
1-Am in o-3,4-d ih yd r o-3-p h en yl-2-n a p h th a len eca r bon i-
tr ile (5e): Rf 0.18 (1:3 EtOAc-hexane); mp 165-167 °C
(hexane-CH2Cl2); IR (KBr disk) 3461, 3364, 3250, 2177, 1634
cm-1; 1H NMR (270 MHz, CDCl3) δ 3.03 (1H, dd, J ) 15.2, 6.9
Hz), 3.25 (1H, dd, J ) 15.2, 6.9 Hz), 3.83 (1H, t, J ) 6.9 Hz),
4.76 (2H, br s), 7.1-7.45 (9H, m); MS (rel intensity) m/ z 246
(M+, 75), 169 (100). Anal. Calcd for C17H14N2: C, 82.90; H,
5.73; N, 11.37. Found: C, 82.81; H, 5.60; N, 11.35.
1-Am in o-3-m eth yl-2-n a p h th a len eca r boxylic a cid (6a ):
Rf 0.47 (1:3 EtOAc-hexane); IR (neat) 3443, 3369, 3232, 1631
1
cm-1; H NMR (270 MHz, CDCl3) δ 2.40 (3H, s), 3.68 (2H, br
s), 6.60 (1H, s), 7.09 (1H, s), 7.3-7.45 (2H, m), 7.65-7.75 (2H,
m); MS (rel intensity) m/ z 201 (M+, 100). Anal. Calcd for
C12H11NO2: C,71.63; H, 5.51; N, 6.96. Found: C, 71.35; H,
5.40; N, 7.09.
Eth yl 1-Am in o-3-ph en yl-2-n aph th alen ecar boxylate (6c):
Rf 0.55 (1:3 EtOAc-hexane); IR (neat) 3487, 3369, 1684, 1602
cm-1; 1H NMR (60 MHz, CCl4) δ 0.67 (3H, t, J ) 7.0 Hz), 3.84
(2H, q, J ) 7.0 Hz), 6.10 (2H, br s), 6.99 (1H, s), 7.2-7.9 (9H,
m); 13C NMR (67.9 MHz, CDCl3) δ 13.1, 60.3, 119.0, 121.3,
122.5, 125.4, 125.6, 126.4, 127.8, 128.0, 128.3, 128.7, 134.9,
140.0, 140.1, 146.3, 170.0; MS (rel intensity) m/ z 291 (M+,
100). Anal. Calcd for C19H17NO2: C, 78.33; H, 5.88; N, 4.81.
Found: C, 78.19; H, 5.71; N, 5.00.
E t h yl 1-Am in o-3,4-d ih yd r o-3,3-d im et h yl-2-n a p h t h a l-
en eca r boxyla te (5f): Rf 0.60 (1:3, EtOAc-hexane); IR (neat)
3468, 3330, 1653, 1614 cm-1 1H NMR (270 MHz, CDCl3) δ
;
1.20 (6H, s), 1.34 (3H, t, J ) 7.3 Hz), 2.65 (2H, s), 4.25 (2H, q,
J
) 7.3 Hz), 6.31 (2H, br s), 7.15-7.4 (4H, m); MS (rel
intensity) m/ z 245 (M+, 21), 230 (100). Anal. Calcd for
C15H19NO2: C, 73.44; H, 7.81; N, 5.71. Found: C, 73.70; H,
7.88; N, 5.59.
1-Am in o-3,4-d ih yd r o-3-m et h yl-4-p h en yl-2-n a p h t h a l-
en eca r bon itr ile (5g): a mixture of diastereomers (ca. 1:3);
Rf 0.27 (1:3, EtOAc-hexane); IR (neat) 3466, 3363, 3255, 2178,
1-Am in o-3-m eth yl-2-n aph th alen ecar bon itr ile (6d):4a mp
146-149 °C (hexane) (lit.4a 146-147 °C); IR (KBr disk) 3450,
3384, 3250, 2204, 1643, 1624 cm-1
; 1H NMR (60 MHz, CCl4) δ
1
1636 cm-1; H NMR (270 MHz, CDCl3) δ 1.08 (2.25 H, d, J )
2.55 (3H, s), 5.1 (2H, br s), 7.03 (1H, s), 7.3-7.9 (4H, m).
1-Am in o-3-p h en yl-2-n a p h th a len eca r bon itr ile (6e): mp
214 °C (CH2Cl2); IR (KBr disk) 3459, 3373, 3246, 2201, 1645
7.3 Hz), 1.14 (0.75 H, d, J ) 6.8 Hz), 2.8-2.9 (0.75 H, m), 3.0-
3.1 (0.25 H, m), 3.79 (0.75 H, d, J ) 7.6 Hz), 4.00 (0.25 H, d,
J ) 5.9 Hz), 4.67 and 4.75 (2H, 2 br s), 6.9-7.5 (9H, m); MS
(rel intensity) m/ z 260 (M+, 28), 245 (100). Anal. Calcd for
C18H16N2: C, 83.05; H, 6.20; N, 10.76. Found: C, 83.00; H,
6.09; N, 10.85.
1
cm-1; H NMR (270 MHz, CDCl3) δ 5.25 (2H, br s), 7.24 (1H,
s), 7.4-7.65 (7H, m),7.75-7.85 (2H, m); MS (rel intensity) m/ z
244 (M+, 100). Anal. Calcd for C17H12N2: C, 83.58; H, 4.95;
N, 11.47. Found: C, 83.53; H, 4.86; N, 11.40.
1-Am in o-3,4-d ih yd r o-3,4-d im eth yl-2-n a p h th a len eca r -
bon itr ile (5h ): a mixture of diastereomers (ca. 1:1); Rf 0.50
(1: 3 EtOAc-hexane); IR (neat) 3465, 3363, 3254, 2178, 1634
cm-1; 1H NMR (270 MHz, CDCl3) δ 1.94 (1.5H, d, J ) 6.9 Hz),
1.09 (1.5H, t, J ) 7.3 Hz), 1.15 (1.5H, d, J ) 7.3 Hz), 1.21
1-Am in o-3-m e t h yl-4-p h e n yl-2-n a p h t h a le n e ca r b on i-
tr ile (6g): Rf 0.47 (1:3 EtOAc-hexane); IR (neat) 3470, 3377,
3254, 2203, 1643 cm-1; 1H NMR (270 MHz, CDCl3) δ 2.30 (3H,
s), 5.12 (2H, br s), 7.15-7.25 (2H, m), 7.3-7.5 (6H, m), 7.75-
7.85 (1H, m); MS (rel intensity) m/ z 258 (M+, 100). Anal.