The Journal of Organic Chemistry
Note
7.80 (dd, J = 8.6 and 7.3 Hz, 1H) ppm. 13C NMR (100 MHz,
DMSO): δ 140.3, 139.3, 134.4, 132.5, 132.1, 130.8, 130.0, 129.8, 117.2,
117.1, 109.0, 108.3 ppm. HRMS (ESI-TOF) m/z: [M]+ calcd for
C12H5BrN2 255.9616, found 255.9647. FT-IR: 3021, 2223, 1565, 1504,
1369, 1044, 986, 840, 814, 760, 615, 558 cm−1.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H12N3O2 278.0930,
found 278.0936. FT-IR: 2996, 2415, 2228, 1741, 1580, 1372, 1345,
1213, 1033, 961, 865, 769, 555 cm−1.
Ethyl 2-[(4,5-Dicyanonaphthalen-1-yl)amino]acetate (13). The
procodure was adapted from Bomann and co-workers’ conditions.14
Iminoacetate 12 (653 mg, 2.36 mmol, 1 equiv) was charged to a 50
mL flask containing a stir bar under argon atmosphere. Methanol (10
mL) was added via syringe forming a suspension. Next, BH3·Py (0.79
mL, 7.78 mmol, 3.3 equiv) was added via syringe, and the reaction
mixture was allowed to stir for 1 h. HCl (6 M, 5 mL, 30 mmol, 12.7
equiv) was added with the evolution of H2 over 10 min, and the
reaction mixture was stirred for 30 min. It was vacuum filtered and
washed with water. Once the filtrate appeared dry, it was dissolved in
DCM, dried on MgSO4, filtered, and concentrated to dryness to give
the N-naphthylglycine 13 as a tan residue (549 mg, 83% yield). Rf =
0.61 (20% EtOAc/DCM). Mp: 172−173 °C (DCM/hexanes). 1H
NMR (400 MHz, DMSO): δ 8.67 (d, J = 8.7 Hz, 1H), 8.29 (d, J = 7.2
Hz, 1H), 8.08 (t, J = 6.1 Hz, 1H), 8.04 (d, J = 8.5 Hz, 1H), 7.74 (t, J =
7.9 Hz, 1H), 6.64 (d, J = 8.5 Hz, 1H), 4.28 (d, J = 6.1 Hz, 2H), 4.19
(q, J = 7.1 Hz, 2H), 1.25 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (100
MHz, DMSO): δ 170.7, 150.1, 140.9, 139.2, 130.8, 129.2, 125.8, 123.0,
119.3, 118.1, 108.0, 105.4, 92.8, 61.7, 45.3, 15.0 ppm. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H13N3O2 280.1086, found
280.1088. FT-IR: 2995, 2209, 1743, 1580, 1345, 1218, 1116, 1021,
809, 750 cm−1.
4-Azidonaphthalene-1,8-dicarbonitrile (6). Compound 6 was
prepared according to literature precedence; however, no experimental
details were provided.8 Caution: explosion hazard when heating azides.
Aryl bromide 10 (5.2 g, 20 mmol, 1 equiv), NaN3 (1.56 g, 24 mmol,
1.2 equiv) and DMSO (80 mL) were charged to a 500 mL flask
containing a stir bar under argon atmosphere. The flask was placed in a
100 °C oil bath and stirred for 30 min. The reaction was cooled to
room temperature and diluted with water (250 mL) the suspended
solid was then filtered. The solid was dissolved in DCM and dried on
MgSO4. It was concentrated to saturation then crystallized with
hexanes (layer method) to give aryl azide 6 as brown fluffy needles
(3.74 g, 85% yield). Rf = 0.33 (100% DCM). Mp: 168−170 °C
1
(DCM/hexanes). H NMR (400 MHz, CDCl3): δ 8.52 (dd, J = 8.6
and 1.3 Hz, 1H), 8.17 (dd, J = 7.3 and 1.3 Hz, 1H), 8.11 (d, J = 8 Hz,
1H), 7.69 (dd, J = 8.6 and 7.3 Hz, 1H), 7.42 (d, J = 8 Hz, 1H) ppm.
13C NMR (100 MHz, CDCl3): δ 143.6, 139.0, 138.1, 130.1, 129.1,
126.9, 126.5, 116.9, 116.7, 114.7, 109.1, 104.6 ppm. HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C12H5N5Na 242.0443, found
242.0444. FT-IR: 3023, 2221, 2109, 1573, 1511, 1409, 1373, 1278,
1444, 1020, 955, 843, 818, 760, 658, 549 cm−1.
2-[(4,5-Dicyanonaphthalen-1-yl)amino]acetic Acid (5). Ethyl
ester 13 (500 mg, 1.79 mmol, 1.0 equiv) and methanol (8 mL)
were charged to a 50 mL flask along with a magnetic stir bar. Water (2
mL) and KOH (221 mg, 3.94 mmol, 2.2 equiv) were next added, and
the reaction mixture immediately became red-orange and cloudy. The
reaction was then stirred for 18 h. The reaction mixture was then
concentrated to remove the methanol. The remaining residue was
diluted with water (20 mL), and the pH was adjusted to 2−3 with
citric acid and the suspended solid was vacuum filtered then washed
with water. The solid was then dissolved in acetone, dried on MgSO4
and filtered. The acetone solution was warmed near boiling and
concentrated to saturation, and a layer of hexanes was placed on top
and allowed to slowly diffuse. Once it cooled to room temperature, it
was placed in a −25 °C freezer overnight. After vacuum filtration, we
obtained free acid 5 as a canary yellow powder (450.3 mg, >95%
yield). Rf = 0.43 (20% EtOAc/DCM). Mp: 210 °C dec (acetone/
4-Aminonaphthalene-1,8-dicarbonitrile (11). Compound 11 was
prepared according to literature precedence; however, no experimental
details were provided.8 Azide 6 (3.67 g, 16.7 mmol, 1 equiv), NaBH4
(1.9 g, 50 mmol, 3 equiv), and THF (50 mL) were charged to a 250
mL round-bottom flask with a stir bar under argon atmosphere fitted
with a reflux condenser. The reaction mixture immediately began to
evolve nitrogen; once the gas evolution slowed, the reaction vessel was
placed in a 65 °C oil bath and stirred for 1 h. The reaction mixture was
cooled to room temperature and concentrated to dryness. It was then
diluted with water (80 mL) and the pH was adjusted to pH 5−6 with
citric acid with hydrogen evolution. The solid was filtered and washed
into a round-bottom with toluene, and the solvent was removed in
vacuo. The residual water was removed by azeotroping with toluene
(3×, 20 mL) and then dried in vacuo overnight to give naphthylamine
11 as a tan powder (3.2 g, > 95% yield). Rf = 0.46 (30% EtOAc/
DCM). Mp: 220 °C dec (THF). 1H NMR (400 MHz, DMSO): δ 8.86
(dd, J = 8.6 and 1.2 Hz, 1H), 8.25 (dd, J = 7.3 and 1.2 Hz, 1H), 7.93
(d, J = 8.4 Hz, 1H), 7.65 (dd, J = 8.6 and 7.3 Hz, 1H), 7.38 (broad, s,
2H), 6.85 (d, J = 8.4 Hz, 1H) ppm. 13C NMR (100 MHz, DMSO): δ
152.4, 140.6, 139.3, 131.3, 130.1, 125.0, 122.2, 119.7, 118.2, 109.0,
107.6, 91.2 ppm. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C12H8N3 194.0718, found 194.0719. FT-IR: 3226, 2214, 1649, 1577,
1521, 1356, 754, 566 cm−1.
Ethyl (2E)-2-[(4,5-Dicyanonaphthalen-1-yl)imino]acetate (12).
Compound 12 was synthesized by analogy from Zhu et al.13
Naphthylamine 11 (868 mg, 4.54 mmol, 1 equiv), Na2SO4 (3.22 g,
22.7 mmol, 5 equiv), and toluene (45 mL,) were charged to a 250 mL
flask containing a stir bar. Ethyl glyoxylate (50%) in toluene (4.75 M,
1.9 mL, 9 mmol, 2 equiv) was next added, and the flask was fitted with
a reflux condenser and placed under argon atmosphere. The reaction
vessel was then placed in a 120 °C oil bath and stirred vigorously for
18 h. The reaction mixture was cooled to room temperature, vacuum
filtered to remove unreacted starting material and Na2SO4, and then
washed with toluene. The filtrate can be collected and resubmitted to
identical reaction conditions for the recycle. The toluene was removed
in vacuo to afford a tan powder. The solid was then washed with ether
(30 mL) to remove excess ethyl glyoxylate and vacuum filtered and
dried in vacuo to give pure anil 12 (550 mg, recycle: 367 mg, 73%
yield). Rf = 0.54 (20% EtOAc/DCM, partial decomposition to 11).
Mp: 205−207 °C (toluene). 1H NMR (400 MHz, DMSO): δ 8.54 (d,
J = 8.5 Hz, 1H), 8.48 (d, J = 7.2 Hz, 1H), 8.45 (d, J = 7.8 Hz, 1H),
8.14 (s, 1H), 7.92 (dd, J = 8.2 and 7.6 Hz, 1H), 7.54 (d, J = 7.8 Hz,
1H), 4.41 (qt, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H) ppm. 13C
NMR (100 MHz, DMSO): δ 171.5, 152.4, 140.7, 139.4, 131.4, 130.2,
125.1, 122.2, 119.7, 118.2, 109.0, 107.7, 91.2, 87.8, 61.1, 15.0 ppm.
1
hexanes). H NMR (400 MHz, DMSO): δ 12.93 (broad, s, 1H), 8.97
(d, J = 8.7 Hz, 1H), 8.29 (d, 7.2 Hz, 1H), 8.04 (d, J = 8.5 Hz, 1H),
8.01 (d, J = 6.1 Hz, 1H), 7.34 (dd, J = 8.6 and 7.4 Hz, 1H), 6.64 (d, J =
8.5 Hz, 1H), 4.18 (d, J = 6.1 Hz, 1H) ppm. 13C NMR (100 MHz,
DMSO): δ 172.1, 150.2, 140.9, 139.1, 130.8, 129.2, 125.7, 123.0, 119.4,
118.1, 107.9, 105.4, 92.5, 45.3 ppm. HRMS (ESI-TOF) m/z: [M]+
calcd for C14H9N3O2 251.0708, found 251.0709. FT-IR: 3411, 3075,
2200, 1753 1580, 1537, 1537, 1428, 1342, 1121, 805, 658. 565 cm−1.
4-[2-(Trimethylsilyl)ethynyl]naphthalene-1,8-dicarbonitrile (15).
A 50% solution of THF/NEt3 (25 mL) was sparged with argon in a
50 mL round-bottom flask for 15 min, while aryl bromide 10 (2.81 g,
10.9 mmol, 1.0 equiv), Pd(PPh3)2Cl2 (70.5 mg, 0.109 mmol, 1 mol
%), and cuprous iodide (41.5 mg, 0.218 mmol, 2 mol %) were charged
to a separate 100 mL round-bottom flask containing a stir bar fitted
with a reflux condenser under argon atmosphere. The solvent mixture
(10 mL) followed by TMS-acetylene and the last half of the solvent
(10 mL) were added to the flask via syringe. The mixture was stirred
vigorously, placed into the 45 °C oil bath, and aged for 18 h. The
reaction could be monitored by removing small aliquots and analyzing
by 1H NMR since the product cospots with starting material on TLC.
The reaction mixture was then allowed to cool to room temperature
and vacuum filtered to remove the ammonium salts. The filtrate was
washed with EtOAc (50 mL). The organics were extracted with water
(20 mL) and then brine (20 mL). The organics were then dried on
MgSO4 and filtered. The solvent was removed in vacuo to afford an
analytically pure brown solid (2.54 g, 85% yield). Mp: 150 °C dec
1
(DCM/hexanes). H NMR (400 MHz, CDCl3): δ 8.74 (dd, J = 8.5
and 1.3 Hz, 1H), 8.18 (dd, J = 7.3 and 1.3 Hz, 1H), 8.07 (d, J = 7.6 Hz,
1H), 7.84 (d, J = 7.6 Hz, 1H), 7.78 (dd, J = 8.5 and 7.3 Hz, 1H), 0.38
D
dx.doi.org/10.1021/jo4009386 | J. Org. Chem. XXXX, XXX, XXX−XXX