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RSC Advances
2-(Naphthalen-1-yl)acetamide (1g).31 Prepared from 2-
(naphthalen-1-yl)acetic acid (0.93 g, 5.0 mmol), SOCl2 (5 equiv.),
and aqueous NH3 (25%, 15 mL) analogously to 1aa. Yield: 0.80 g
3.37 (t, J ¼ 7.6 Hz, 1H), 2.20–2.11 (m, 1H), 1.83–1.74 (m, 1H),
1.37–1.18 (m, 4H), 0.87 (t, J ¼ 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d/ppm: 176.2, 140.0, 128.8, 127.9, 127.3, 52.8, 32.6, 29.8,
22.5, 13.9; IR (neat) ~n/cmꢁ1: 3381m, 3174w, 2933m, 1651s,
1455w, 1413m, 1301w, 1126w, 816w, 755w, 719m, 697s; HRMS
(ESI-Orbitrap) m/z: calcd for C12H17NO [M + H]+ 192.1383, found
192.1386.
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(86%). Physical state: white powder. Mp 162–165 C; H NMR
(400 MHz, DMSO-d6) d/ppm: 8.09 (d, J ¼ 7.7 Hz, 1H), 7.93–7.91
(m, 1H), 7.81 (dd, J ¼ 6.7, 2.5 Hz, 1H), 7.56–7.44 (m, 5H), 6.93
(br s, 1H), 3.87 (s, 2H); 13C NMR (100 MHz, DMSO-d6) d/ppm:
172.0, 133.3, 132.8, 132.0, 128.2, 127.7, 126.9, 125.8, 125.5,
125.4, 124.2, 39.7; IR (neat) ~n/cmꢁ1: 3361w, 3178w, 1659m,
1620m, 1512w, 1397m, 1291w, 1261w, 775s; HRMS (ESI-
Orbitrap) m/z: calcd for C12H12NO [M + H]+ 186.0913, found
186.0916.
2,2-Diphenylacetamide (1d).37 Prepared from 2,2-diphenyl-
acetic acid (1.06 g, 5.0 mmol), SOCl2 (5 equiv.), and aqueous
NH3 (25%, 15 mL) analogously to 1aa. Yield: 0.78 g (74%).
Physical state: white powder. Mp 169–171 ꢀC; 1H NMR (400
MHz, DMSO-d6) d/ppm: 7.69 (br s, 1H), 7.33–7.28 (m, 8H), 7.24–
7.21 (m, 2H), 7.09 (br s, 1H), 4.94 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) d/ppm: 173.0, 140.5, 128.5, 128.2, 126.6, 56.3; IR
(neat) ~n/cmꢁ1: 3386w, 3172w, 1651s, 1496m, 1405m, 1260m,
1103w, 1034w, 845w, 738m, 722m, 697s; HRMS (ESI-Orbitrap)
m/z: calcd for C14H14NO [M + H]+ 212.1070, found 212.1075.
2-Hydroxy-2,2-diphenylacetamide (1da).32 Prepared from
methyl benzilate (2.42 g, 10.0 mmol) analogously to 1b. Yield:
2-(Thiophen-2-yl)acetamide (1h).41 Prepared from 2-
(thiophen-2-yl)acetic acid (0.71 g, 5.0 mmol), SOCl2 (5 equiv.),
and aqueous NH3 (25%, 15 mL) analogously to 1aa. Yield: 0.42 g
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(60%). Physical state: white powder. Mp 115–117 C; H NMR
(400 MHz, DMSO-d6) d/ppm: 7.44 (br s, 1H), 7.33 (dd, J ¼ 5.1,
1.3 Hz, 1H), 6.95–6.90 (m, 3H), 3.60 (s, 2H); 13C NMR (100 MHz,
DMSO-d6) d/ppm: 171.2, 137.8, 126.5, 126.0, 124.8, 36.4; IR
(neat) ~n/cmꢁ1: 3347m, 3157m, 1633s, 1405s, 1287m, 1258m,
1128w, 1040w, 828w, 760w, 694s; HRMS (ESI-Orbitrap) m/z:
calcd for C6H8NOS [M + H]+ 142.0321, found 142.0325.
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1.29 g (57%). Physical state: white powder. Mp 153–155 C; H
NMR (400 MHz, DMSO-d6) d/ppm: 7.42–7.39 (m, 5H), 7.36 (br s,
1H), 7.33–7.24 (m, 6H), 6.52 (s, 1H); 13C NMR (100 MHz, DMSO-
d6) d/ppm: 175.1, 144.2, 127.4, 126.9, 80.2; IR (neat) ~n/cmꢁ1
:
2-(6-Methoxynaphthalen-2-yl)propanenitrile (2a).42 Phosgene
(15% in toluene, 4.3 mL, 6 mmol) was added dropwise to
a suspension of naproxamide (1a, 0.46 g, 2.0 mmol) in dry
toluene (6 mL) and THF (2 mL) at rt under Ar. Aer the TLC
(SiO2) n-hexane–EtOAc (3 : 1) revealed a complete consumption
of starting material (ca. 4 h), the reaction was quenched with
water. The layers were separated, the organic phase was washed
with a saturated aqueous solution of NaHCO3 and brine, dried
over anhydrous Na2SO4, ltered, and evaporated in vacuo. Yield:
0.34 g (80%). Physical state: white powder. Mp 90–91 ꢀC; 1H
NMR (400 MHz, CDCl3) d/ppm: 7.87–7.84 (m, 3H), 7.48 (dd, J ¼
8.5, 1.9 Hz, 1H), 7.34 (d, J ¼ 2.5 Hz, 1H), 7.20 (dd, J ¼ 9.0, 2.5 Hz,
1H), 4.40 (q, J ¼ 7.2 Hz, 1H), 3.88 (s, 3H), 1.62 (d, J ¼ 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) d/ppm: 157.5, 133.6, 132.5, 129.2,
128.2, 127.6, 125.2, 125.1, 122.3, 119.1, 105.8, 55.2, 29.8, 20.5; IR
(neat) ~n/cmꢁ1: 2962w, 1727w, 1602m, 1505w, 1482w, 1448w,
1393w, 1258m, 1212m, 1085w, 1022m, 927w, 890m, 856s, 816m;
HRMS (ESI-Orbitrap) m/z: calcd for C14H12NO [M ꢁ H]ꢁ
210.0924, found 210.0926.
3384w, 1682s, 1494w, 1445m, 1155w, 1049m, 903w, 755m, 696s;
HRMS (ESI-Orbitrap) calcd for C14H12O2N [M ꢁ H]ꢁ 226.0874 m/
z, found 226.0873 m/z.
2-(2-Fluoro-[1,10-biphenyl]-4-yl)propanamide (1e).37 Prepared
from urbiprofen (1.22 g, 5.0 mmol), SOCl2 (5 equiv.), and
aqueous NH3 (25%, 15 mL) analogously to 1aa. The precipitated
product was ltered off, washed with a saturated solution of
NaHCO3, water, toluene, and dried in vacuo. Yield: 1.07 g (87%).
Physical state: white powder. Mp 125–126 ꢀC; 1H NMR (400
MHz, DMSO-d6): 7.54–7.37 (m, 7H), 7.26–7.23 (m, 2H), 6.95
(br s, 1H), 3.65 (q, J ¼ 7.0 Hz, 1H), 1.35 (t, J ¼ 7.0 Hz, 3H); 13C
NMR (100 MHz, DMSO-d6): 174.8, 158.8 (d, J ¼ 245.6 Hz), 144.4
(d, J ¼ 7.7 Hz), 135.1, 130.5, 128.7, 128.6, 127.8, 126.3 (d, J ¼ 12.5
Hz), 123.9, 114.9 (d, J ¼ 23.1 Hz), 44.5, 18.2; 19F NMR (376 MHz,
DMSO-d6): ꢁ118.76 to ꢁ118.82 (m, 1F); IR (neat) ~n/cmꢁ1
:
3360m, 3181m, 1656s, 1482m, 1422m, 1397s, 1282m, 1130w,
1090w, 1011w, 932m, 869w, 830w, 764m, 694s; HRMS (ESI-
Orbitrap) m/z: calcd for C15H15NOF [M + H]+ 244.1132, found
244.1138.
2-Hydroxy-2-phenylacetonitrile (2ba).43 The solution of
benzaldehyde (0.41 mL, 4.0 mmol) and acetic acid (0.57 mL, 10
mmol) in dry Et2O (6 mL) was added dropwise to a suspension
of KCN (0.65 g, 10 mmol) in dry Et2O (30 mL) at ꢁ5 ꢀC under Ar.
The resulting reaction mixture was allowed to warm to rt slowly
and stirred overnight. Then the reaction mass was diluted with
water (30 mL), the organic phase was separated and washed
repetitively with a 20% aqueous solution of NaHSO3 to remove
residues of the starting aldehyde. Next, it was washed with
a saturated aqueous solution of NaHCO3 and brine, dried over
anhydrous Na2SO4, ltered, and evaporated in vacuo. Yield:
2-(4-Isobutylphenyl)propanamide (1f).37 Prepared from
ibuprofen (1.03 g, 5.0 mmol), SOCl2 (5 equiv.), and aqueous NH3
(25%, 15 mL) analogously to 1aa. The precipitated product was
ltered off, washed with a saturated solution of NaHCO3, water,
toluene, and dried in vacuo. Yield: 0.98 g (95%). Physical state:
white powder. Mp 112–113 ꢀC; 1H NMR (400 MHz, DMSO-d6) d/
ppm: 7.33 (br s, 1H), 7.22–7.20 (m, 2H),7.08–7.06 (m, 2H), 6.77
(br s, 1H), 3.52 (q, J ¼ 7.0 Hz, 1H), 2.40 (d, J ¼ 7.1 Hz, 2H), 1.85–
1.75 (m, 1H), 1.29 (d, J ¼ 7.0 Hz, 3H), 0.85 (d, J ¼ 6.6 Hz, 6H); 13
C
NMR (100 MHz, DMSO-d6) d/ppm: 175.4, 139.7, 139.1, 128.7,
127.0, 44.5, 44.3, 29.6, 22.2, 18.5; IR (neat) ~n/cmꢁ1: 3342m,
3164m, 2958m, 1633s, 1515w, 1460m, 1406m, 1367m, 1265w,
1115w, 1070w, 999w, 841w; HRMS (ESI-Orbitrap) m/z: calcd for
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0.43 g (83%). Physical state: colorless oil. H NMR (400 MHz,
CDCl3) d/ppm: 7.53–7.43 (m, 5H), 5.52 (s, 1H), 3.25 (br s, 1H);
13C NMR (100 MHz, CDCl3) d/ppm: 135.1, 129.8, 129.2, 126.6,
118.8, 63.5; IR (neat) ~n/cmꢁ1: 3413br, 1494w, 1455m, 1261w,
C
13H20NO [M + H]+ 206.1539, found 206.1545.
This journal is © The Royal Society of Chemistry 2020
RSC Adv., 2020, 10, 25029–25045 | 25037