2-(arylamino)aryliminophosphoranes as easily available and convenient starting materials in the synthesis of 1,2,3-benzotriazoles

Article abstract of DOI:10.1055/s-0034-1378448

1-Aryl-1,2,3-benzotriazole systems are synthesized in the high-yielding cyclocondensation of 2-(arylamino)aryliminophosphoranes under mild conditions. The reaction concludes the three-step, halogen-free synthetic route starting from simple nitroarenes and

Full text of DOI:10.1055/s-0034-1378448

LETTER
▌1987
letter
2-(Arylamino)aryliminophosphoranes as Easily Available and Convenient
Starting Materials in the Synthesis of 1,2,3-Benzotriazoles
Synthesis of 1-Arylbenzotriazoles from Aryliminophosphoranes
Emilia Łukasik, Zbigniew Wróbel*
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw 42, Poland
Fax +48(22)6326681; E-mail: zbigniew.wrobel@icho.edu.pl
Received: 08.05.2014; Accepted after revision: 10.06.2014
starting materials in the synthesis of benzotriazole deriva-
Abstract: 1-Aryl-1,2,3-benzotriazole systems are synthesized in
tives.
the high-yielding cyclocondensation of 2-(arylamino)arylimino-
phosphoranes under mild conditions. The reaction concludes the
three-step, halogen-free synthetic route starting from simple ni-
troarenes and arylamines.
When a solution of 2-(arylamino)iminophosphorane 1 in
AcOH was treated with 1.1 equivalents of NaNO2, the
corresponding 1-aryl-1,2,3-benzotriazole 2 and triphenyl-
phosphine oxide were formed almost immediately (Table
1).13,14 In most cases the products were formed in high or
nearly quantitative yields. The reaction seems to be insen-
sitive for both electrophilicity of the arylamine ring (Table
1, entries 2, 9, 12, 14, and 16) and steric factor (Table 1,
entries 1, 3,10, and 15). The 4-methoxy group in the aryli-
mine ring may bring some disturbances, from lower yield
of product (Table 1, entry 4) to different reaction course.
Sodium nitrite was added to the reaction mixture as a solid
although in one case its addition as a concentrated aque-
ous solution gave better results (Table 1, entry 5).
Key words: cyclization, condensation, heterocycles, annulation,
ylides
The benzotriazole motif is present in a number of bioac-
tive molecules such as antifungal compounds,1 antiprolif-
erative agents and histone deacetylase inhibitors,2
serotonine receptors,3 as agonists for many proteins,4 and
as other active drugs,5 for example, vorozole and al-
izapride (Figure 1).
Cl
N
This way we completed a halogen-free (omitting SNAr
displacement of a halogen in 2-halonitroarene with ani-
line) three-step sequence from nitroarenes and anilines via
N-aryl-2-nitrosoanilines and 2-(arylamino)arylimino-
phosphoranes to 1-N-aryl-1,2,3-benzotriazoles (Scheme
1).
O
N
N
N
Me
N
N
H
N
N
N
H
MeO
N
N
vorozole
alizapride
Figure 1 Examples of drugs containing benzotriazole scaffold
NO2
N
A few synthetic ways leading to 1-aryl-1,2,3-benzotri-
azoles were reported. The simplest one was the reaction of
N-aryl-1,2-arylenediamines with nitrosating agent such as
sodium or alkyl nitrite in acidic media.6 More sophisticat-
ed methods included metal-catalyzed arylation of 1,2,3-
benzotriazole,7 reaction of benzobisoxadisiloles with aryl
azides,8 SNAr substitution of fluorine in activated arenes
by benzotriazole nitrogen,9 or reaction of aryl azides with
in situ generated benzynes.10
N
+
ArNH2
N
X
X
Ar
2
PPh3
O
N
N
NHAr
NHAr
X
X
In 2013 we reported a straightforward synthesis of 2-
(arylamino)aryliminophosphoranes11 from easily accessi-
ble N-aryl-2-nitrosoanilines, synthesized directly from ni-
troarenes and anilines.12 Their application in the synthesis
of 2-aminobenzimidazole derivatives was demonstrat-
ed.11
1
Scheme 1 Three steps from nitroarenes to 1-arylbenzotriazoles
For the sake of this work a number of new 2-(arylami-
no)aryliminophosphoranes were synthesized proving the
generality and versatility of the previously reported proto-
col (see Supporting Information).11
In this communication we would like to report that the ti-
tle compounds could be successively used as convenient
It should be mentioned that 2-(arylamino)aryliminophos-
phoranes are much more stable than the corresponding 2-
arylaminoanilines. Although no quantitative investiga-
tions were undertaken so far, we observed that the former
could be stored at room temperature for months without
SYNLETT 2014, 25, 1987–1990
Advanced online publication: 28.07.2014
DOI: 10.1055/s-0034-1378448; Art ID: st-2014-b0399-l
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

1988
E. Łukasik, Z. Wróbel
LETTER
Table 1 Synthesis of 1-Aryl-1,2,3-benzotriazoles from 1a
tion occurs differently. Although it appears to be of
general character some exceptions were observed
(Scheme 3).
PPh3
N
N
N
H
NaNO2
AcOH
N
N
Ar
NH2
X
Ar
NHAr
X
1
2
Entry
1
X
Ar
Product Yield
(%)b,c
X
a
1
2
1a
1b
1c
1d
1e
1f
4-Cl
4-Cl
2,6-Me2C6H3
4-MeC6H4
2,6-Me2C6H3
4-MeC6H4
4-MeC6H4
4-EtOC6H4
4-MeC6H4
4-MeC6H4
4-py
2a
2b
2c
4
99
PPh3
N
N
90
O
N
NHAr
N
Ph3P
N
O
Ph3P
N
N
N
3
4-Cl-6-MeO
4-MeO
4-Ph
93
b
X
Ar
NAr
NAr
2
X
4
50 (0)
50 (74)
97
1
5
2e
2f
X
X
O
N
6
4-Cl-6-MeO
4-F
+
+
+
PPh3
N2
PPh3
–N
7
1g
1h
1i
2g
2h
2i
85
N
NHAr
NHAr
NHAr
c
8
4-Ph
92
9
4-Cl
96
X
X
X
3
10
11
12
13
14
15
16
17
1j
4-Cl
2-MeC6H4
4-ClC6H4
2j
96
Scheme 2 Possible mechanistic routes of the reaction
1k
1l
4-F
2k
2l
84
4-Cl
4-CNC6H4
4-MeOC6H4
66
Ph3P
N
H
N
N
N
NaNO2
AcOH
1m
1n
1o
1p
1q
4-Cl
2m
2n
2o/5
69
N
Ar
Ar
4-Cl
2-Br-4-ClC6H3
2,6-Me2C6H3
97
O2N
4-F
41/30
73
X
X
1d X = OMe, Ar = 4-MeC6H4
1o X = F; Ar = 2,6-Me2C6H3
4 50%
4-Cl
3,5-(MeO)2C6H3 2p
4-MeC6H4 2q
5 30% + 2o
4-Br
77
–N
a Iminophosphorane (1 mmol) in AcOH (5mL) at 0 °C, treated with
powdered NaNO2 in one portion.
Ph3P
+N
Bu
Bu
N
NaNO2
AcOH
b The yields when NaNO2 was added as a concentrated aqueous solu-
tion are shown in parentheses.
N
N
36%
c Isolated yields.
Cl
Cl
O
F
6
1r
any noticeable changes, whereas the later underwent slow
decomposition observed on TLC plate. This implies the
use of 2-(arylamino)aryliminophosphoranes as stable and
convenient 2-arylaminoaniline equivalents.
Ph3P
N
N
H
N
H
N
O
NaNO2
AcOH
N
Concerning the mechanistic pathway of the reaction we
considered three possibilities (Scheme 2). In situ hydroly-
sis of substrate 1 to arylenediamine followed by the reac-
tion of the latter with nitrous acid (pathway a) was ruled
out since the 2-(arylamino)iminophosphoranes were sta-
ble in acetic acid under the reaction conditions. Pathway
b seems to be very likely, comprising well-documented
N-nitrosation of diarylamines followed by intramolecular
condensation of iminophoshoryl group with a nitroso
group, a process analogous to the aza Wittig reaction.
Pathway c, although without any precedence in the litera-
ture, apparently takes place in a few cases when the reac-
OMe
O
1s
7
Scheme 3 Some uncommon products of the reaction
The presence of +M substituents (1d) made the arene ring
prone to nitrosation/oxidation resulting in the formation
of nitro compound 4. On the other hand, formation of 6
from 1r with blocked arylamine position as well as 7 from
1s suggest pathway b, that is, nitrosation of the imine ni-
trogen followed by formation of intermediate diazonium
Synlett 2014, 25, 1987–1990
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of 1-Arylbenzotriazoles from Aryliminophosphoranes
(11) Łukasik, E.; Wróbel, Z. Synlett 2014, 25, 217.
1989
derivative 3 (Scheme 2). The latter, in turn, bearing a very
strong electron-withdrawing diazonium group, was sus-
ceptible to aromatic nucleophilic substitution of a leaving
group in position para with water (for 1r) followed by
deprotonation to form diazoketone 6. For 1s the nucleo-
philic demethylation of appropriate 3 via an intermediate
similar to 6 proceeded, followed by hydrolysis of diazoke-
tone to quinone 7.15 Structures 4–7 were fully character-
ized by NMR, MS, and IR spectra.
(12) (a) Wróbel, Z.; Kwast, A. Synlett 2007, 1525. (b) Wróbel,
Z.; Kwast, A. Synthesis 2010, 3865.
(13) Synthesis of 1-Aryl-1,2,3-benzotriazoles 2 – General
Procedure
Iminophosphorane 1 (1 mmol) was dissolved in AcOH (5
mL), cooled down to 0 °C, and NaNO2 (1.1 mmol) was
added portionwise with stirring. The reaction was stirred
until completion (TLC control, usually 5–20 min). The
mixture was poured into H2O, extracted with EtOAc, dried
with Na2SO4, and the solvent was evaporated. The crude
product was purified by column chromatography.
(14) Analytical Data for Representative Products
Compound 2a: white solid; mp 152–154 °C. 1H NMR (400
MHz, CDCl3): δ = 1.92 (s, 6 H), 7.21 (d, J = 2.0 Hz, 1 H),
7.25 (s, 1 H), 7.27 (s, 1 H), 7.37–7.42 (m, 2 H), 8.08 (d, J =
8.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 17.5, 112.3,
118.3, 127.0, 129.1, 131.1, 132.9, 134.8, 136.3, 142.6,
145.2. MS (EI): m/z (%) = 259 (13), 257 (40), 228 (39), 216
(13), 214 (39), 194 (100), 193 (22). HRMS (EI): m/z calcd
for C14H12N335Cl: 257.0720; found: 257.0730.
Since the presented method enables smooth synthesis of
1-aryl-1,2,3-benzotriazoles in three steps, an efficient se-
quence via a ‘halogen-free’ way could be regarded as
valuable alternative to other known methods.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
Compound 2b: pink crystals; mp 136–138 °C. 1H NMR (500
MHz, CDCl3):16 δ = 2.40 (s, 3 H), 7.30 (dd, J = 8.8, 1.8 Hz,
1 H), 7.33–7.36 (m, 2 H), 7.52–7.55 (m, 2 H), 7.65 (d, J =
1.8 Hz, 1 H), 7.98 (d, J = 8.8 Hz, 1 H). 13C NMR (125 MHz,
CDCl3): δ = 21.2, 110.2, 121.1, 122.9, 125.5, 130.5, 133.0,
134.0, 134.6, 139.2, 150.0. MS (EI): m/z (%) = 245 (16), 243
(51), 216 (29), 215 (44), 214 (76), 180 (100), 179 (12).
HRMS (EI): m/z calcd for C13H10N335Cl: 243.0563; found:
243.0563.
References and Notes
(1) (a) Sudhir, M. S. A.; Nadh, R. V.; Radhika, S. Drug Invent.
Today 2013, 5, 126.
(2) Li, X.; Fu, J.; Shi, W.; Luo, Y.; Zhang, X.; Zhu, H.; Yu, H.
Bull. Korean Chem. Soc. 2013, 34, 2387.
(3) Boido, A.; Boido, C. C.; Sparatore, F. Farmaco 2001, 56,
263.
(4) Kale, R. R.; Prasad, V.; Mohapatra, P. P.; Tiwari, V. K.
Monatsh. Chem. 2010, 141, 1159.
Compound 2c: white solid; mp 92–95 °C. 1H NMR (400
MHz, DMSO-d6): δ = 1.84 (s, 6 H), 4.11 (s, 3 H), 6.94–7.01
(m, 2 H), 7.33–7.39 (m, 2 H), 7.45–7.51 (m, 1 H). 13C NMR
(100 MHz, DMSO-d6): δ = 16.9, 56.9, 101.5, 105.9, 128.8,
130.6, 133.3, 134.9, 135.4, 135.8, 135.9, 151.7. MS (EI): m/z
(%) = 289 (51), 288 (29), 287 (100), 258 (24), 246 (37), 245
(23), 224 (78), 218 (16), 217 (10), 216 (51), 209 (39), 201
(21), 181 (52), 180 (39). HRMS (EI): m/z calcd for
C15H14N3O35Cl: 287.0825; found: 287.0828.
(5) Piccionello, A. P.; Guarcello, A. Curr. Bioact. Compd. 2010,
6, 266.
(6) (a) Znoiko, S. A.; Kambolova, A. S.; Maizlish, V. E.;
Shaposhnikov, G. P.; Abramov, I. G.; Filimonov, S. I. Russ.
J. Gen. Chem. 2009, 79, 1735. (b) Nolan, K. A.; Humphries,
M. P.; Barnes, J.; Doncaster, J. R.; Caraher, M. C.; Tirelli,
N.; Bryce, R. A.; Whitehead, R. C.; Stratford, I. J. Bioorg.
Med. Chem. 2010, 18, 696. (c) Fujiwara, C.; Hagaya, M.;
Kakuta, H.; Kawata, K.; Nakayama, M.; Ohsawa, F.; Ohta,
Y.; Shinozaki, R.; Yakushiji, N.; Yamada, Sh.; Makishima,
M.; Uno, Sh.; Tai, A.; Maehara, A.; Nakayama, M.;
Oohashi, T.; Yasui, H.; Yoshikawa, Y. ACS Med. Chem.
Lett. 2012, 3, 427. (d) Barnes, J.; Bryce, R. A.; Caraher, M.
C.; Doncaster, J. R.; Humphries, M. P.; Nolan, K. A.;
Stratford, I. J.; Tirelli, N.; Barnes, J.; Doncaster, J. R.;
Whitehead, R. C. Bioorg. Med. Chem. 2010, 18, 696.
(e) Kulagowski, J. J.; Moody, C. J.; Rees, C. W. J. Chem.
Soc., Perkin Trans. 1 1985, 2733.
(7) (a) Beletskaya, I. P.; Davydov, D. V.; Moreno-Mañas, M.
Tetrahedron Lett. 1998, 39, 5617. (b) Mukhopadhyay, C.;
Tapaswi, P. K. Synth. Commun. 2012, 42, 2217. (c) Antilla,
J. C.; Barder, T. E.; Baskin, J. M.; Buchwald, S. L. J. Org.
Chem. 2004, 69, 5578. (d) Alakonda, L.; Periasamy, M.
Synthesis 2012, 44, 1063. (e) Jena, A. K.; Mohapatra, S.;
Panda, N.; Rout, S. R. Tetrahedron Lett. 2011, 52, 1924.
(8) (a) Cao, W.; Chen, J.; Chen, Y.; Lin, Y.; Ma, X.; Xu, D.
Tetrahedron 2011, 67, 856. (b) Chen, Y.-L.; Sun, J.-Q.; Wei,
X.; Wong, W.-Y.; Lee, A. W. M. J. Org. Chem. 2004, 69,
7190.
Compound 2e: yellow solid; mp 110–112 °C. 1H NMR (400
MHz, DMSO-d6): δ = 3.87 (s, 3 H), 7.19–7.25 (m, 2 H),
7.40–7.44 (m, 1 H), 7.46–7.2 (m, 2 H), 7.76–7.80 (m, 3 H),
7.81–7.86 (m, 2 H), 7.93 (s, 1 H), 8.19–8.25 (m, 1 H). 13
C
NMR (100 MHz, DMSO-d6): δ = 55.6, 108.2, 115.1, 119.9,
124.4, 124.8, 127.6, 128.0, 129.0, 129.3, 132.8, 139.6,
140.8, 145.0, 159.4. MS (EI): m/z (%) = 301 (20), 273 (45),
259 (22), 258 (100), 231 (14), 230 (68), 228 (10). HRMS
(EI): m/z calcd for C19H15N3O: 301.1215; found: 301.1219.
Compound 2f: white solid; mp 116–119 °C. 1H NMR (500
MHz, DMSO-d6): δ = 1.36 (t, J = 7.0 Hz, 3 H), 4.06 (s, 3 H),
4.11 (q, J = 7.0 Hz, 2 H), 6.96 (d, J = 1.5 Hz, 1 H), 7.14–7.17
(m, 2 H), 7.35 (d, J = 1.5 Hz, 1 H), 7.67–7.70 (m, 2 H). 13
NMR (125 MHz, DMSO-d6): δ = 15.0, 57.2, 64.1, 102.9,
106.1, 115.9, 125.3, 129.1, 134.6, 134.9, 136.8, 151.8,
C
159.4. MS (EI): m/z (%) = 305 (39), 304 (21), 303 (82), 248
(53), 247 (49), 246 (100), 240 (58), 232 (37), 218 (37), 212
(87), 211 (12), 204 (51), 203 (26), 188 (20). HRMS (EI): m/z
calcd for C15H14N3O235Cl: 303.0775; found: 303.0769.
Compound 2g: orange solid; mp 123–126 °C. 1H NMR (500
MHz, DMSO-d6): δ = 2.41 (s, 3 H), 7.36-7.41 (m, 1 H),
7.44–7.47 (m, 2 H), 7.70–7.73 (m, 3 H), 8.20–8.23 (m, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 21.1, 97.4 (d, JCF = 29
Hz), 114.8 (d, JCF = 27 Hz), 122.0 (d, JCF = 7 Hz), 123.1,
130.9, 132.7 (d, JCF = 14 Hz), 134.1, 139.1, 143.1, 162.6 (d,
JCF = 244 Hz). MS (EI): m/z (%) = 227 (48), 199 (50), 198
(100), 184 (25). HRMS (EI): m/z calcd for C13H10N3F:
227.0859; found: 227.0859.
(9) (a) Song, T.; Xu, L.; Zhao, J.; Zhao, J.; Zhu, S. Tetrahedron
2011, 67, 910. (b) Rosevear, J.; Wilshire, J. F. K. Aust. J.
Chem. 1991, 44, 1097.
(10) (a) Ankati, H.; Biehl, E. Tetrahedron Lett. 2009, 50, 4677.
(b) Moses, J. E.; Zhang, F. Org. Lett. 2009, 11, 1587.
(c) Chen, Y.; Larock, R. C.; Shi, F.; Waldo, J. P. Org. Lett.
2008, 10, 2409.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1987–1990

1990
E. Łukasik, Z. Wróbel
LETTER
Compound 2h: orange solid; mp 109–111 °C. 1H NMR (400
MHz, CDCl3): δ = 2.52 (s, 3 H), 7.37–7.42 (m, 3 H), 7.43–
7.50 (m, 2 H), 7.61–7.64 (m, 2 H), 7.65–7.69 (m, 3 H), 7.82–
7.84 (m, 1 H), 8.15–8.19 (m, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 21.4, 108.5, 120.5, 123.2, 124.9, 127.9, 128.2,
129.1, 130.6, 133.3, 134.7, 139.1, 140.8, 142.1, 146.0. MS
(EI): m/z (%) = 285 (21), 258 (21), 257 (100), 256 (64), 140
(16), 139 (17). HRMS (EI): m/z calcd for C19H15N3:
285.1266; found: 285.1266.
13C NMR (100 MHz, CDCl3): δ = 17.6, 95.5 (d, JCF = 27 Hz),
114.2 (d, JCF = 27 Hz), 121.8 (d, JCF = 11 Hz), 128.9, 130.6,
133.9, 134.4 (d, JCF = 14 Hz), 136.6, 142.5, 163.0 (d, JCF
=
248 Hz). MS (EI): m/z (%) = 241 (68), 213 (36), 212 (100),
211 (17), 199 (24), 198 (83). HRMS (EI): m/z calcd for
C14H12N3F: 241.1015; found: 241.1013.
Compound 2p: white solid; mp 134–137 °C. 1H NMR (400
MHz, CDCl3): δ = 3.88 (s, 6 H), 6.59 (t, J = 2.0 Hz, 1 H),
6.88–6.90 (m, 2 H), 7.49 (dd, J = 8.8, 1.6 Hz, 1 H), 7.77 (d,
J = 1.6 Hz, 1 H), 8.05 (d, J = 8.8 Hz, 1 H). 13C NMR (100
MHz, CDCl3): δ = 55.9, 100.8, 101.5, 110.6, 121.3, 125.8,
133.0, 134.9, 138.2, 145.2, 161.8. MS (EI): m/z (%) = 291
(32), 290 (16), 289 (83), 261 (33), 246 (28), 227 (22), 226
(100), 218 (49), 203 (44), 183 (18). HRMS (EI): m/z calcd
for C14H12N3O235Cl: 289.0618; found: 289.0623.
Compound 2i: white solid, mp 155–158 °C. 1H NMR (500
MHz, DMSO-d6): δ = 7.58–7.62 (m, 1 H), 8.02–8.04 (m, 2
H), 8.24–8.29 (m, 1 H), 8.30–8.33 (m, 1 H), 8.84–8.87 (m, 2
H). 13C NMR (125 MHz, DMSO-d6): δ = 111.9, 116.3,
121.9, 126.5, 132.3, 135.0, 143.1, 145.3, 152.1. MS (EI): m/z
(%) = 232 (31), 230 (68), 204 (46), 203 (20), 202 (91), 167
(48), 140 (53). HRMS (EI): m/z calcd for C11H7N435Cl:
230.0359; found: 230.0359.
Compound 2q: white solid; mp 142–144 °C. 1H NMR (400
MHz, CDCl3): δ = 2.48 (s, 3 H), 7.39–7.44 (m, 2 H), 7.52
(dd, J = 8.8, 1.6 Hz, 1 H), 7.58–7.63 (m, 2 H), 7.88 (d, J =
1.6 Hz, 1 H), 8.00 (d, J = 8.8 Hz, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 21.3, 113.5, 121.5, 122.6, 123.1, 128.1, 130.6,
133.6, 134.2, 139.4, 145.4. MS (EI): m/z (%) = 289 (24), 287
(24), 261 (21), 260 (31), 259 (22), 258 (29), 181 (26), 180
(100), 179 (23), 178 (11). HRMS (EI): m/z calcd for
C13H10N379Br: 287.0058; found: 287.0061.
Compound 4: white solid; mp 122–124 °C. IR (film;
CH2Cl2): νmax = 1531 (NO2) cm–1. 1H NMR (500 MHz,
CDCl3): δ = 2.50 (s, 3 H), 4.00 (s, 3 H), 7.11 (s, 1 H), 7.44–
7.47 (m, 2 H), 7.57–7.60 (m, 2 H), 8.56 (s, 1 H). 13C NMR
(125 MHz, CDCl3): δ = 21.3, 57.0, 92.2, 118.0, 123.2, 130.7,
133.6, 134.4, 138.9, 139.5, 139.8, 153.3. MS (EI): m/z (%) =
284 (100), 241 (41), 211 (21), 210 (90), 196 (11), 183 (33),
181 (28), 180 (80). HRMS (EI): m/z calcd for C14H12N4O3:
284.0909; found: 284.0918.
Compound 2j: orange oil. 1H NMR (500 MHz, CDCl3): δ =
2.13 (s, 3 H), 7.35–7.44 (m, 4 H), 7.46–7.54 (m, 2 H), 8.08
(d, J = 8.8 Hz, 1 H). 13C NMR (125 MHz, DMSO-d6): δ =
17.7, 109.9, 121.0, 125.4, 126.8, 127.1, 130.3, 131.8, 134.5,
134.6, 134.7, 135.3, 144.2. MS (EI): m/z (%) = 245 (20), 243
(43), 217 (19), 216 (36), 215 (40), 214 (74), 200 (21), 180
(100). HRMS (EI): m/z calcd for C13H10N335Cl: 243.0563;
found: 243.0562.
Compound 2k: white solid; mp 200–202 °C. 1H NMR (400
MHz, CDCl3): δ = 7.19–7.25 (m, 1 H), 7.34–7.37 (m, 1 H),
7.57–7.62 (m, 2 H), 7.68–7.72 (m, 2 H), 8.09–8.13 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 96.3 (d, JCF = 29 Hz),
114.6 (d, JCF = 26 Hz), 122.1 (d, JCF = 11 Hz), 124.0, 130.4,
132.7 (d, JCF = 14 Hz), 134.9, 135.3, 143.5, 163.1 (d, JCF
=
248 Hz). MS (EI): m/z (%) = 247 (24), 219 (47), 185 (15),
184 (100), 158 (13), 157 (11). HRMS (EI): m/z calcd for
C12H7N335ClF: 247.0313; found: 247.0322.
Compound 5: colorless oil. 1H NMR (400 MHz, CDCl3): δ =
1.93 (s, 6 H), 7.08 (d, J = 9.2 Hz, 1 H), 7.29–7.31 (m, 2 H),
7.43–7.47 (m, 1 H), 8.95 (d, J = 6.4 Hz, 1 H). 13C NMR (100
MHz, CDCl3): δ = 17.6, 98.2 (d, JCF = 26 Hz), 119.8, 129.2,
131.2, 133.1, 135.6 (d, JCF = 12 Hz), 136.4, 139.4, 140.2,
155.5. MS (EI): m/z (%) = 286 (86), 241 (15), 228 (13), 213
(34), 212 (100), 211 (70), 210 (38), 209 (21), 185 (21).
HRMS (EI): m/z calcd for C14H11N4O2F: 286.0866; found:
286.0869.
Compound 6: brown oil. IR (film; CH2Cl2): νmax = 2094
(>=N=N), 1713 (C=O stretching) cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.89–0.94 (m, 3 H), 1.28–1.38 (m, 2 H), 1.57–
1.66 (m, 2 H), 3.62–3.66 (m, 2 H), 6.21 (d, J = 1.6 Hz, 1 H),
6.30 (dd, J = 9.6, 1.6 Hz, 1 H), 6.99–7.02 (m, 2 H), 7.05 (d,
J = 9.6 Hz, 1 H), 7.30–7.33 (m, 2 H). 13C NMR (100 MHz,
CDCl3): δ = 13.9, 20.3, 29.3, 54.6, 109.5, 113.6, 124.8,
125.0, 129.0, 130.3, 130.7, 144.7, 150.0, 183.1.
Compound 2l: white solid; mp 224–226 °C. IR (film;
CH2Cl2): νmax = 2226 (CN) cm–1. 1H NMR (400 MHz,
CDCl3): δ = 7.47 (dd, J = 8.8, 2.8 Hz, 1 H), 7.96 (d, J = 2.8
Hz, 1 H), 7.93–7.99 (m, 4 H), 8.11 (d, J= 8.8 Hz, 1 H). 13
C
NMR (100 MHz, CDCl3): δ = 110.2, 112.7, 117.9, 121.9,
122.7, 125.0, 126.4, 132.5, 134.2, 136.0, 140.1. MS (EI): m/z
(%) = 256 (17), 254 (49), 228 (44), 226 (99), 192 (23), 191
(100), 102 (56). HRMS (EI): m/z calcd for C13H7N435Cl:
254.0359; found: 254.0358.
Compound 2m: white solid, mp 170–172 °C. 1H NMR (400
MHz, CDCl3): δ = 3.91 (s, 3 H), 7.09–7.13 (m, 2 H), 7.37
(dd, J = 8.8, 1.6 Hz, 1 H), 7.60–7.64 (m, 2 H), 7.65 (d, J =
1.6 Hz, 1 H), 8.04 (d, J = 8,8 Hz, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 55.8, 110.2, 115.2, 121.2, 124.7, 125.5, 129.6,
133.4, 134.6, 144.9, 160.2. MS (EI): m/z (%) = 261 (13), 259
(39), 218 (34), 216 (100), 196 (90), 190 (21), 189 (10), 188
(66), 181 (20), 153 (35). HRMS (EI): m/z calcd for
C13H10N3O35Cl: 259.0512; found: 259.0513.
Compound 7: orange solid; mp 199–200 °C. IR (film;
CH2Cl2): νmax = 3253 (NH), 1693 (C=O stretching) cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.22 (s, 6 H), 5.45 (s, 1 H),
7.14–7.23 (m, 3 H), 7.28 (s, 1 H), 7.66–7.69 (m, 1 H), 8.41–
8.44 (m, 1 H), 8.96–8.98 (m, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 18.1, 102.4, 128.4, 128.6, 129.0, 130.9, 133.3,
134.4, 135.8, 147.0, 147.2, 153.3, 180.4, 182.2. MS: m/z =
279.2 [M + H]. Anal. Calcd (%) for C17H14N2O2: C, 73.37;
H, 5.07; N, 10.06. Found: C, 73.22; H, 5.26; N, 9.95.
(15) (a) Sundberg, R. J.; Baxter, E. W.; Pitts, W. J.; Ahmed-
Schofield, R.; Nishiguchi, T. J. Org. Chem. 1988, 53, 5097.
(b) Adam, W.; Hadjiarapoglou, L.; Mielke, K.; Treiber, A.
Tetrahedron Lett. 1994, 5625.
Compound 2n: white solid, mp 135–138 °C. 1H NMR (400
MHz, CDCl3): δ = 7.36 (d, J = 2 Hz, 1 H), 7.41 (dd, J = 8.8,
2.4 Hz, 1 H), 7.45–7.49 (m, 1 H), 7.54–7.57 (m, 1 H), 7.86
(d, J = 2.4 Hz, 1 H), 8.08 (d, J = 8.8 Hz, 1 H). 13C NMR (100
MHz, CDCl3): δ = 110.3, 121.4, 121.6, 125.8, 129.2, 130.2,
134.1, 134.3, 135.2, 137.5, 144.4 (one signal not visible).
MS (EI): m/z (%) = 343 (25), 340 (13), 314 (16), 279 (21),
277 (16), 236 (65), 234 (100), 199 (20), 198 (18), 164 (26).
HRMS (EI): m/z calcd for C12H6N335Cl279Br: 340.9122;
found: 340.9127.
Compound 2o: colorless oil. 1H NMR (400 MHz, CDCl3):
δ = 1.93 (s, 6 H), 6.84–6.87 (m, 1 H), 7.17–7.22 (m, 1 H),
7.25–7.27 (m, 2 H), 7.37–7.41 (m, 1 H), 8.10–8.14 (m, 1 H).
(16) Mukhopadhyay, C.; Tapaswi, P. K.; Butcher, R. J. Org.
Biomol. Chem. 2010, 8, 4720.
Synlett 2014, 25, 1987–1990
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