The Journal of Organic Chemistry
Article
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2.55 (t, J = 7.5 Hz, 2H, rotamer B), 2.34−2.29 (m, 2H, rotamer A),
2.28 (s, 3H, rotamer A), 2.27 (s, 3H, rotamer B). 13C{1H} NMR
(CDCl3, 100 MHz) δ 155.3 (rotamer A), 154.7 (rotamer B), 149.1
(rotamer B), 149.0 (rotamer A), 142.6 (rotamer B), 142.4 (rotamer
B), 142.3 (rotamer A), 141.9 (rotamer A), 141.3 (rotamer A), 137.85
(d, 1Jcp = 12.5 Hz, rotamer B, Ph′ or Ph″), 137.84 (d, 1Jcp = 12.5 Hz,
= 25.0 Hz), 37.7, 28.4 (d, JCP = 14.0 Hz). 31P{1H} NMR (CDCl3,
162 MHz) δ −22.5. FTIR (ATR/νmax) 3066−2961, 1688, 1595,
1493, 1451, 1433, 1393, 1351, 1307, 1295, 1283, 1151, 1040 cm−1.
HRMS (ESI) m/z: [M + H]+ calcd for C22H23NO2P 364.1461; found
364.1458.
Synthesis of 2-(Diphenylphosphanyl)ethyl Mesityl(methyl)-
carbamate (23). Following the general procedure 3, 9 (0.26 g, 1.40
mmol) was treated with 2-(diphenylphosphino)ethanol (0.32 g, 1.40
mmol), 4-dimethylaminopyridine (0.018 g, 0.14 mmol), and triethyl-
amine (0.38 mL, 2.80 mmol) to provide 23 (0.20 g, 35%) as a white
solid after silica-gel column chromatography (hexane/acetone 95/5)
followed by crystallization via vapor diffusion using a mixture of n-
hexane and ethyl acetate to obtain colorless single crystals. Mp 93−95
°C. 1H NMR (CDCl3, 400 MHz) δ 7.53−7.23 (m, 10H, rotamer A +
rotamer B), 6.88 (s, 2H, rotamer A + rotamer B), 4.33 (AA′BB′, 2H,
rotamer B), 4.15 (AA′BB′, 2H, rotamer A), 3.11 (s, 3H, rotamer A),
2.98 (s, 3H, rotamer B), 2.52 (AA′BB′, 2H, rotamer B), 2.33
(AA′BB′, 2H, rotamer A), 2.28 (s, 3H, rotamer A), 2.26 (s, 3H,
rotamer B), 2.14 (s, 6H, rotamer A + rotamer B). 13C{1H} NMR
(CDCl3, 100 MHz) δ 156.0 (rotamer A) 155.0 (rotamer A), 138.2
(rotamer A + rotamer B), 137.9 (d, 1Jcp = 12.5 Hz, rotamer A), 137.7
1
rotamer B, Ph′ or Ph″), 137.66 (d, Jcp = 12.5 Hz, rotamer A, Ph″),
137.64 (d, 1Jcp = 12.5 Hz, rotamer A, Ph′), 132.74 (d, 2Jcp = 18.0 Hz,
2
rotamer B, Ph′ or Ph″), 132.72 (d, Jcp = 18.5 Hz, rotamer B, Ph′ or
2
2
Ph″), 132.60 (d, Jcp = 18.5 Hz, rotamer A, Ph″), 132.56 (d, Jcp
=
18.5 Hz, rotamer A, Ph′), 132.0 (rotamer B), 131.7 (rotamer A),
3
128.9 (rotamer B), 128.8 (rotamer A), 128.74 (d, Jcp = 6.0 Hz,
rotamer B), 128.70 (d, 3Jcp = 7.5 Hz, rotamer A), 128.5 (rotamer A +
rotamer B), 123.8 (rotamer B), 123.7 (rotamer A), 63.7 (d, 3Jcp = 26.0
Hz, rotamer A), 63.6 (d, 3Jcp3 = 23.0 Hz, rotamer B), 35.8 (rotamer B),
3
35.7 (rotamer A), 28.4 (d, Jcp = 14.5 Hz, rotamer B), 28.3 (d, Jcp
=
15.0 Hz, rotamer A), 18.43 (rotamer A), 18.40 (rotamer B), 14.3
(rotamer A + rotamer B). 31P{1H} NMR (CDCl3, 162 MHz) δ
−22.15 (rotamer B), −23.37 (rotamer A). FTIR (ATR/νmax) 3081−
2932, 1724, 1586, 1529, 1513, 1491, 1422, 1344, 1304, 1252, 1113,
1085 cm−1. HRMS (ESI) m/z: [M + H]+ calcd for C24H26N2O4P
437.1625; found 437.1624. As an example of signal NMR assignment
for these self-immolative systems, further NMR analyses were carried
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(d, Jcp = 12.5 Hz, rotamer B), 137.7 (rotamer A), 137.1 (br. s,
rotamer A + rotamer B), 135.4 (rotamer B), 135.3 (rotamer A), 132.8
(d, Jcp = 19.0 Hz, rotamer B), 132.7 (d, Jcp = 19.0 Hz, rotamer A),
129.3 (rotamer B), 129.1 (rotamer A), 128.8 (rotamer B), 128.7
2
2
Synthesis of 2-(Diphenylphosphanyl)ethyl Methyl(2,4,6-trimeth-
yl-3-nitrophenyl)carbamate (21). Following the general procedure 3,
7 (0.36 g, 0.82 mmol) was treated with 2-(diphenylphosphino)-
ethanol (0.32 g, 1.40 mmol), 4-dimethylaminopyridine (0.018 g, 0.14
mmol), and triethylamine (0.38 mL, 2.80 mmol) to provide 21 (0.11
g, 30%) as a colorless oil with a 74:26 mixture of rotamers A/B after
3
3
(rotamer A), 128.6 (d, Jcp2 = 7.0 Hz, rotamer B), 128.5 (d, Jcp = 6.5
2
Hz, rotamer A), 63.3 (d, Jcp = 28.0 Hz, rotamer A), 63.2 (d, Jcp
=
23.0 Hz, rotamer B), 35.99 (rotamer B), 35.97 (rotamer A), 28.5 (d,
1Jcp = 14.5 Hz, rotamer B), 28.3 (d, 1Jcp = 14.5 Hz, rotamer A), 21.11
(rotamer A), 21.06 (rotamer B), 17.75 (rotamer A), 17.72 (rotamer
B). 31P{1H} NMR (CDCl3, 162 MHz) δ −22.0 (rotamer B), −23.1
(rotamer A). FTIR (ATR/νmax) 3049−2915, 1707, 1655, 1584, 1483,
1454, 1432, 1390, 1348, 1308, 1277, 1217, 1172, 1148, 1097, 1070,
1027 cm−1. HRMS (ESI) m/z: [M + H]+ calcd for C25H29NO2P
406.1924; found 406.1930.
General Procedure 4 for the Synthesis of Carbamate Model
Compounds (24−28). Sodium hydride (NaH, 60% dispersion in
mineral oil, 1.1 equiv) was added to a solution of 2-naphthaleneme-
thanol (1 equiv) in anhydrous DMF (10 mL) at 0 °C and left to stir
for 15 min. Carbamoyl chloride (1 equiv) was added, and the mixture
was left to stir overnight. The salts formed were filtered off, and
volatiles were removed in vacuo. The crude product was further
purified by column chromatography, followed by recrystallization via
vapor diffusion using a mixture of n-hexane and ethyl acetate to obtain
colorless single crystals.
Synthesis of Naphthalen-2-ylmethyl Methyl(4-nitrophenyl)-
carbamate (24). Following the general procedure 4, 2-naphthalene-
methanol (0.122 g, 0.77 mmol) was treated with NaH (0.034 g, 0.85
mmol) and 1 (0.166, 0.77 mmol) to provide 24 (0.200 g, 77%) as a
white solid after silica-gel column chromatography (hexane/EtOAc
75/25). Mp 109−111 °C. 1H NMR (CDCl3, 400 MHz) δ 8.21 (d, J =
9.0 Hz, 2H), 7.88−7.80 (m, 4H), 7.67−7.34 (m, 5H), 5.38 (s, 2H),
3.42 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ 154.8, 149.0,
144.6, 133.31, 133.28, 128.6, 128.1, 127.9, 127.7, 126.6, 125.9, 124.7,
124.4, 68.5, 37.2. FTIR (ATR/νmax) 3057−2963, 1709, 1602, 1590,
1512, 1442, 1329, 1257, 1160, 1104 cm−1. HRMS (ESI) m/z: [M +
Na]+ calcd for C19H16O4N2Na 359.1002; found 359.0999.
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silica-gel column chromatography (hexane/acetone 95/5). H NMR
(CDCl3, 400 MHz) δ 7.50−7.27 (m, 10H, rotamer A + rotamer B),
7.01 (s, 1H, rotamer B), 6.99 (s, 1H, rotamer A), 4.35 (dt, 2H, 3JHP
=
3
9.5 Hz, J = 7.5 Hz rotamer B), 4.16 (AA′BB′, 2H, rotamer A), 3.11
(s, 3H, rotamer A), 2.97 (s, 3H, rotamer B), 2.52 (app. t, 3J = 8.0 Hz,
3H rotamer B), 2.31 (app. t, 3J = 8.0 Hz, 2H, rotamer A), 2.27 (s, 3H,
rotamer A), 2.26 (s, 3H, rotamer B), 2.19 (s, 3H, rotamer A +
rotamer B), 2.12 (s, 3H, rotamer A), 2.11 (s, 3H, rotamer B).
13C{1H} NMR (CDCl3, 100 MHz) δ 155.5 (rotamer A), 154.9
(rotamer B), 151.0 (rotamer B), 150.9 (rotamer A), 139.6 (rotamer
B), 139.1 (rotamer A), 138.8 (rotamer B), 138.6 (rotamer A), 137.90
(d, 1Jcp = 12.0 Hz, rotamer B, Ph′ or Ph″), 137.87 (d, 1Jcp = 12.0 Hz,
1
rotamer B, Ph′ or Ph″), 137.72 (d, Jcp = 12.0 Hz, rotamer A, Ph′ or
1
Ph″), 137.68 (d, Jcp = 12.0 Hz, rotamer A, Ph′ or Ph″), 132.85 (d,
2
2JCP = 18.0 Hz, rotamer B, Ph′ or Ph″), 132.82 (d, JCP = 19.0 Hz,
2
rotamer B, Ph′ or Ph″), 132.77 (d, Jcp = 18.0 Hz, rotamer A, Ph″),
2
132.69 (d, Jcp = 18.5 Hz, rotamer A, Ph′), 131.0 (rotamer B), 130.9
(rotamer A), 129.0−128.5 (m, 7C), 128.3 (rotamer B), 128.0
2
2
(rotamer A), 63.74 (d, Jcp = 25.5 Hz, rotamer A), 63.68 (d, Jcp
=
24.0 Hz, rotamer B), 36.0 (rotamer B), 35.9 (rotamer A), 29.2 (d, 1Jcp
= 14.5 Hz, rotamer B), 28.4 (d, Jcp = 15.0 Hz, rotamer A), 18.0
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(rotamer A), 17.9 (rotamer B), 17.5 (rotamer A), 17.4 (rotamer B),
13.1 (rotamer A + rotamer B). 31P{1H} NMR (CDCl3, 162 MHz) δ
−22.1 (rotamer B), −23.3 (rotamer A). FTIR (ATR/νmax) 3054−
2932, 1702, 1524, 1480, 1454, 1433, 1388, 1345, 1311, 1284, 1220,
1152, 1124, 1095, 1027 cm−1. HRMS (ESI) m/z: [M + H]+ calcd for
C25H28N2O4P 451.1781; found 451.1766.
Synthesis of Naphthalen-2-ylmethyl Methyl(2-methyl-4-
nitrophenyl)carbamate (25). Following the general procedure 4, 2-
naphthalenemethanol (0.122 g, 0.77 mmol) was treated with NaH
(0.034 g, 0.85 mmol) and 2 (0.176 g, 0.77 mmol) to provide 25
(0.197 g, 73%) as an off-white solid after silica-gel column
Synthesis of 2-(Diphenylphosphanyl)ethyl Methyl(phenyl)-
carbamate (22). Following the general procedure 3, 8 (0.24 g, 1.40
mmol) was treated with 2-(diphenylphosphino)ethanol (0.32 g, 1.40
mmol), 4-dimethylaminopyridine (0.018 g, 0.14 mmol), and triethyl-
amine (0.38 mL, 2.80 mmol) to provide 22 (0.30 g, 59%) as a white
solid after silica-gel column chromatography (hexane/EtOAc 95/5 →
90/10) followed by crystallization via vapor diffusion using a mixture
of n-hexane and ethyl acetate to obtain colorless single crystals. Mp
53−55 °C. 1H NMR (CDCl3, 400 MHz) δ 7.47−7.37 (m, 4H),
7.37−7.29 (m, 8H), 7.25−7.17 (m, 3H), 4.27 (q, J = 7.5 Hz, 2H),
3.22 (s, 3H), 2.44 (t, J = 7.5 Hz, 2H). 13C{1H} NMR (CDCl3, 100
MHz) δ 155.5, 143.3, 137.9 (d, 1JCP = 12.2 Hz), 132.8 (d, 2JCP = 18.9
Hz), 128.9 (×2), 128.7 (d, 3JCP = 6.7 Hz), 126.1, 125.8, 63.5 (d, 2JCP
1
chromatography (hexane/EtOAc 75/25). Mp 99−101 °C. H NMR
(CDCl3, 400 MHz) δ 8.08 (br. s, 1H, rotamer A + rotamer B), 8.09−
8.04 (m, 1H, rotamer A + rotamer B), 7.90−7.71 (m, 3H, rotamer A
+ rotamer B), 7.63 (br. s, 1H, rotamer A + rotamer B), 7.55−7.44 (m,
2H, rotamer A + rotamer B), 7.38−7.27 (m, 2H, rotamer A + rotamer
B), 5.43−5.18 (m, 2H, rotamer A + rotamer B), 3.24 (br. s, 3H,
rotamer A + rotamer B), 2.32 (s, 3H, rotamer B), 2.24 (s, 3H, rotamer
A). 13C{1H} NMR (CDCl3, 100 MHz) δ 154.8, 147.4, 146.6, 137.7,
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J. Org. Chem. 2021, 86, 10263−10279