N-Acylbenzotriazoles
J . Org. Chem., Vol. 65, No. 24, 2000 8213
organic layers were dried over anhydrous MgSO4. Evaporation
of the solvent gave a solid, which was recrystallized from
benzene to afford the pure primary amide 3a -n . The isolated
yields, melting points, and reported melting points of 3a -n
are summarized in Table 2.
Sch em e 3
Gen er a l P r oced u r e for th e Rea ction of N-Acylben zo-
tr ia zoles 2 w ith P r im a r y Am in es. The N-acylbenzotriazole
2 (1 mmol) was stirred with the appropriate primary amine
(1 mmol) in THF (10 mL) at room temperature for 4 h. After
evaporation of solvents in vacuo, the residue was added to 2
M NaOH (20 mL) and extracted with EtOAc. The combined
organic layers were dried over anhydrous MgSO4. Evaporation
of the solvent gave a secondary amide 4a -j, which was
recrystallized from appropriate solvents.
Gen er a l P r oced u r e for th e Rea ction of N-Acylben zo-
tr ia zoles 2 w ith Secon d a r y Am in es. The same procedure
as the preparation of the secondary amides 4 afforded pure
tertiary amides 5a -k .
Gen er a l P r oced u r e for th e P r ep a r a tion of r-Hyd r oxy-
a m id es. A mixture of BtSO2CH3 (0.49 g, 2.5 mmol), 2-hydroxy-
2-phenylacetic acid (0.38 g, 2.5 mmol), and Et3N (0.35 g, 3.5
mmol) was refluxed in dry THF for about 20 min, and then
an appropriate amine (2.5 mmol) was added and the mixture
was refluxed for 18 h. After the mixture was concentrated,
EtOAc (50 mL) was added, and the organic phase was washed
with 2 M NaOH and dried over anhyd MgSO4. Removal of the
solvent gave a solid, which was recrystallized from CHCl3 to
furnish R-hydroxyamide 7a ,b.
2-Hyd r oxy-N,2-d ip h en yla ceta m id e (7a ): yield 68%; col-
orless flakes; mp 143-144 °C (lit.28 mp 150-151 °C); 1H NMR
δ 9.08 (br s, 1H), 7.59-7.51 (m, 2H), 7.49-7.40 (m, 2H), 7.40-
7.20 (m, 5H), 7.07 (t, J ) 7.4 Hz, 1H), 6.07 (br s, 1H), 5.13 (s,
1H); 13C NMR δ 170.5 (CdO), 139.7, 137.2, 128.4, 127.9, 127.6,
126.3, 123.7, 119.2, 73.8. Anal. Calcd for C14H13NO2: C, 73.99;
H, 5.77; N, 6.16. Found: C, 73.72; H, 5.91; N, 6.14.
tive substituents; (2) the use of acyl chlorides is avoided;
(3) most N-acylbenzotriazoles can be recrystallized and
are stable to storage over months; (4) workup is very
simple; (5) primary, secondary and tertiary amides were
generally obtained in good to excellent yields; (6) the
method could be extended to R-hydroxyamides and per-
fluoroalkylated amides.
Exp er im en ta l Section
1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded
on a 300 NMR spectrometer in CDCl3 (with TMS for 1H and
CDCl3 for 13C as the internal reference). 19F NMR spectra were
recorded on a 300 NMR spectrometer at 282 MHz in CDCl3
with CFCl3 as an internal reference.
Mod ified P r oced u r e for th e P r ep a r a tion of N-(1-
Meth a n esu lfon yl)ben zotr ia zole (1). To an ice-cold solution
of benzotriazole (11.9 g, 0.10 mol) and pyridine (12.0 g, 0.16
mol) in dry toluene (120 mL) was added dropwise methylsul-
fonyl chloride (9.3 mL, 0.12 mol) in toluene (30 mL). The
mixture was then stirred overnight at room temperature.
AcOEt (150 mL) and H2O (100 mL) were added. The organic
layer was separated, successively washed with water and
brine, and dried over anhydrous MgSO4. Removal of solvents
in vacuo gave a solid, which was recrystallized from benzene
to afford N-(1-methanesulfonyl)benzotriazole (1) (17.5 g, 89%)
as colorless needles: mp 110-112 °C (mp11,29 110-112 °C).
Gen er a l P r oced u r e for th e P r ep a r a tion of N-Acylben -
zotr ia zoles 2. A mixture of aromatic or aliphatic acid (10.0
mmol) and 1-(methylsulfonyl)benzotriazole 1 (1.97 g, 10.0
mmol) and triethylamine (2.0 mL, 14.0 mmol) were refluxed
in THF (50 mL) overnight. The solvent was evaporated and
the residue was dissolved in chloroform (100 mL). The organic
layer was washed with water, dried over anhydrous MgSO4,
and evaporated to give a crude product, which was recrystal-
lized from an appropriate solvent to give pure N-(arylcarbonyl)-
or N-(alkanecarbonyl)benzotriazole 2a -q.
2-H yd r oxy-N -(4-m e t h ylp h e n yl)-2-p h e n yla ce t a m id e
(7b): yield 72%; colorless flakes; mp 169-170 °C (lit.28 mp
1
170-172 °C); H NMR δ 9.02 (br s, 1H), 7.53-7.45 (m, 4H),
7.37-7.24 (m, 1H), 7.33 (d, J ) 7.5 Hz, 2H), 7.09 (d, J ) 8.3
Hz, 2H), 6.11 (d, J ) 4.4 Hz, 1H), 5.14 (d, J ) 4.2 Hz, 1H),
2.29 (s, 3H); 13C NMR δ 170.2 (CdO), 139.9, 134.7, 133.1,
128.8, 127.8, 127.5, 126.3, 119.1, 73.7, 20.3. Anal. Calcd for
C
15H15NO2: C, 74.67; H, 6.27; N, 5.80. Found: C, 74.43; H,
6.63; N, 5.77.
P r epar ation of1-(1H-1,2,3-Ben zotr iazol-1-yl)-2,2,3,3,4,4,4-
h ep ta flu or obu ta n -1-on e (8). To a solution of BtTMS (1.9 g,
10 mmol) in dry THF (20 mL) under argon was added dropwise
n-C3F7COCl (2.3 g, 10 mmol). The mixture was stirred at room
temperature for 3 h. Then, removal of the solvent afforded
C3F7COBt (8), together with byproduct BtH. The 1H NMR
spectrum of the mixture shows that the molar ratio of these
two compounds is 6:1.
1H -1,2,3-Ben zot r ia zol-1-yl(2-m et h oxyp h en yl)m et h a -
n on e (2b): yield 72%; colorless flakes (recrystallized from
1
ethanol); mp 96-97 °C; H NMR δ 8.38 (d, J ) 8.4 Hz, 1H),
8.12 (d, J ) 8.4 Hz, 1H), 7.69 (t, J ) 7.5 Hz, 1H), 7.63-7.50
(m, 3H), 7.14-7.05 (m, 2H), 3.77 (s, 3H); 13C NMR δ 166.9
(CdO), 157.8, 146.0, 133.5, 131.4, 130.2, 130.1, 126.1, 122.6,
120.4, 120.0, 114.4, 111.7, 55.7 (CH3). Anal. Calcd for
1-(1H -1,2,3-Ben zot r ia zol-1-yl)-2,2,3,3,4,4,4-h ep t a flu o-
r obu ta n -1-on e (8): white powder (a mixture with benzotria-
1
zole with ratio as 6:1); yield determined by H NMR, 86%; 1H
NMR δ 8.28 (d, J ) 8.1 Hz, 1H), 8.22 (d, J ) 8.1 Hz, 1H), 7.79
(t, J ) 7.2 Hz, 1H), 7.65 (t, J ) 7.2 Hz, 1H); 19F NMR δ -80.7
(t, J ) 9.3 Hz, 3F, CF3), -112.5 to -112.7 (m, 2F, -CF2CO-),
-124.8 (s, 2F, -CF2-).
Gen er a l P r oced u r e for th e Rea ction of 8 w ith P r im a r y
a n d Secon d a r y Am in es. The mixture of 8 and BtH (212 mg,
0.63 mmol of 8) and an appropriate amine (0.63 mmol) was
stirred at room temperature for 6 h. After being concentrated,
the mixture was washed with 2 M NaOH and extracted with
EtOAc (20 mL × 2). The organic phase was dried over anhyd
MgSO4. Removal of the solvent in vacuo afforded perfluoro-
alkylated amide 9a -d . The isolated yields of 9a -d were based
on n-C3F7COBt.
C
14H11N3O2: C, 66.38; H, 4.38; N, 16.60. Found: C, 66.53; H,
4.41; N, 16.66.
1H -1,2,3-Be n zot r ia zol-1-yl(3-ch lor op h e n yl)m e t h a -
n on e (2c): yield 74%; colorless needles (recrystallized from
1
chloroform/hexane); mp 120-121 °C; H NMR δ 8.38 (d, J )
8.4 Hz, 1H), 8.20-8.11 (m, 3H), 7.75-7.65 (m, 2H), 7.60-7.53
(m, 2H); 13C NMR δ 165.3 (CdO), 145.7, 134.6, 133.6, 133.1,
132.1, 131.5, 130.6, 129.8, 129.7, 126.6, 120.3, 114.7. Anal.
Calcd for C13H8ClN3O: C, 60.60; H, 3.13; N, 16.31. Found: C,
60.75; H, 3.01; N, 16.38.
Gen er a l P r oced u r e for th e Rea ction of N-Acylben zo-
tr ia zoles 2 w ith Aqu eou s Am m on ia . The N-acylbenzotria-
zole 2 (2.5 mmol) was stirred with ammonium hydroxide (30%
aqueous solution, 5 mL, 43 mmol) in EtOH (5 mL) and THF
(5 mL) at room temperature for 2-4 h. After evaporation of
solvents in vacuo, 2 M NaOH (20 mL) was added to the residue
and the mixture then extracted with EtOAc. The combined
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra data and CHN analyses or HRMS for compounds 2d -
f,l-n ,p , 4c,f-i, 5d ,f,h ,i,k , and 9a -d . This material is avail-
(29) Beveridge, S.; Huppatz, J . L. Aust. J . Chem. 1972, 25, 1341.
J O000792F