A facile synthesis of 1-substituted 3-alkoxy-1h-isoindoles based on the reaction of 2-(dialkoxymethyl)phenyllithiums with nitriles, followed by acid-catalyzed cyclization

Article abstract of DOI:10.1002/hlca.201400333

A two-step synthesis of 1-substituted 3-alkoxy-1H-isoindoles 4 has been developed. Thus, the reaction of 2-(dialkoxymethyl)phenyllithium compounds, which are easily generated in situ by Br/Li exchange between 1-bromo-2-(dialkoxymethyl)benzenes 1 and BuLi

Full text of DOI:10.1002/hlca.201400333

Helvetica Chimica Acta – Vol. 98 (2015)
279
A Facile Synthesis of 1-Substituted 3-Alkoxy-1H-isoindoles Based on the
Reaction of 2-(Dialkoxymethyl)phenyllithiums with Nitriles, Followed by
Acid-Catalyzed Cyclization
by Minami Kuroda and Kazuhiro Kobayashi*
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81-857-315263; e-mail: kkoba@chem.tottori-u.ac.jp)
A two-step synthesis of 1-substituted 3-alkoxy-1H-isoindoles 4 has been developed. Thus, the
reaction of 2-(dialkoxymethyl)phenyllithium compounds, which are easily generated in situ by Br/Li
exchange between 1-bromo-2-(dialkoxymethyl)benzenes 1 and BuLi in THF at ꢀ 788, with nitriles
afforded [2-(dialkoxymethyl)phenyl]methanimines 2, which were treated with a catalytic amount of
TsOH · H2O in refluxing CHCl3 to give the desired products in reasonable yields. Similarly, 3-aryl-1-
ethoxy-1-methyl-1H-isoindoles 7 have been prepared starting from 1-bromo-2-(1,1-diethoxyethyl)ben-
zenes 5.
Introduction. – 3-Alkoxy-1H-isoindole derivatives have received much attention,
because some of them have been shown to be useful precursors for the construction of
structurally complex and biologically important molecules, such as 2,3,4,6-tetrahydro-
pyrimido[2,1-a]isoindoles [1], phthalazines [2], and pyrido[2,1-a]isoindoles [3]. To
date, 3-alkoxy-1H-isoindoles have been commonly prepared by treating 2,3-dihydro-
1H-isoindol-1-ones with F3CSO3Me [3] or R3OþBFꢀ4 [4], while an elegant preparation
by the Pd-catalyzed reaction of 2-alkynylbenzonitriles with aryl iodides has also been
reported [5]. In the course of our studies on the development of new methods for the
preparation of benzo-fused heterocycles [6], in which reactions of 2-(1,1-dialkoxy-
alkyl)phenyllithium compounds [7] with various electrophiles are utilized, it was
anticipated that 3-alkoxy-1H-isoindoles could be prepared via the reaction of 2-
(dialkoxymethyl)phenyllithiums with nitriles, followed by acid-catalyzed cyclization of
the resulting [2-(dialkoxymethyl)phenyl]methanimines. We herein report the results of
our investigation, which offer a new and facile two-step approach toward the
preparation of 1-substituted 3-alkoxy-1H-isoindoles 4 from 1-bromo-2-(dialkoxy-
methyl)benzenes 1.
Results and Discussion. – Our two-step synthesis of 4 from 1 was conducted
according to the procedure outlined in Scheme 1. Compounds 1 were easily prepared
from the respective 2-bromobenzaldehydes as described in [1], and were subjected to
Br/Li exchange with BuLi in THF at ꢀ 788 to generate 2-(dialkoxymethyl)phenyl-
lithium derivatives as described in [6]. These Li compounds were then allowed to react
with nitriles to afford, after aqueous workup, the corresponding imines 2 in generally
good yields (cf. Table). Not only aromatic nitriles but also an aliphatic nitrile, i.e., 2,2-
ꢀ 2015 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 98 (2015)
Scheme 1
Table. Preparation of 1-Substituted 3-Alkoxy-1H-isoindoles 4
Entry
1
R4
2
Yield [%]a)
4
Yield [%]a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a (R1 ¼ R2 ¼ H, R3 ¼ Et)
Ph
2a
2b
2c
95
87
81
66
36
81
82
69
72
68
68
68
4a [12a] 65
1a
3-ClꢀC6H4
4b
76
80
70
63
43
52
64
66
57
69
65
57
63
1a
1a
1a
4-ClꢀC6H4
4c [2]
4d [13]
4e
4-MeOꢀC6H4 2d
tBu
2e
2f
2g
2h
2i
2j
2k
2l
1b (R1 ¼ R2 ¼ H, R3 ¼ Me)
Ph
4f [12]
4g
1b
3-ClꢀC6H4
1c (R1 ¼ Cl, R2 ¼ H, R3 ¼ Et)
Ph
4h
4i
1c
3-ClꢀC6H4
1d (R1 ¼ MeO, R2 ¼ H, R3 ¼ Et) Ph
4j
4k
4l
1d
3-ClꢀC6H4
1e (R1 ¼ R2 ¼ MeO, R3 ¼ Et)
Ph
1e
1e
3-ClꢀC6H4
2m 65
2n 60
4m
4n
4-ClꢀC6H4
a) Yields of the isolated products.
dimethylpropanenitrile, was used in this reaction; however, the yield of the product was
rather lower than those from aromatic nitriles (Entry 5). Unfortunately, the reaction of
2-(diethoxymethyl)phenyllithium with propanenitrile gave only a trace amount of the
expected imine. The failure is assumed to be attributable to the abstraction of the a-H-
atom of propanenitrile by the Li compound. Since the imines 2 were somewhat
unstable during separation by column chromatography on usual acidic SiO2, their
isolation was achieved by using neutral SiO2.
Subsequently, [2-(dialkoxymethyl)phenyl]methanimines 2 were converted to the
desired 3-alkoxy-1H-isoindole derivatives 4. After preliminary some experiments,
CHCl3 proved to be a solvent superior to others, such as CH2Cl2 and toluene. When
these imines 2 were treated with a catalytic amount of TsOH · H2O (10 mol-%) in
refluxing CHCl3, cyclization by substitution of one of the alkoxy groups by the imino N-
atom, giving the strained 3-substituted 1-alkoxy-1H-isoindole intermediate 3, pro-

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281
ceeded gradually, and a quick double-bond migration took place to give rise to the less
strained 1-substituted 3-alkoxy-1H-isoindoles 4. No spots corresponding to the
intermediates 3 could be observed by TLC during the reaction. The yields of 4 are
also compiled in the Table, which indicate that generally fair yields were obtained. The
products carrying electron-donating group(s) on the 1H-isoindole benzene ring or an
electron-withdrawing group on the 1-aryl ring were formed more smoothly than the
others, though there was no significant difference in the yields of the products. It should
be noted that the yields of 3-MeO derivatives 4f and 4g (Entries 6 and 7) were rather
lower than those of the corresponding 3-EtO derivatives 4a and 4b, respectively
(Entries 1 and 2). This may be attributable to the difference of lability between 3-MeO
and 3-EtO derivatives toward the acidic reaction conditions. Therefore, (ꢁ)-camphor-
10-sulfonic acid (CSA) could be used in this cyclization. Although the reactions
appeared to proceed more cleanly than those with TsOH · H2O, extended reaction
times were required, and no significant improvement of the yields of the products was
observed.
To probe the preparation of 1-alkoxy-1H-isoindole derivatives 7, 1-bromo-2-(1,1-
diethoxyethyl)benzenes 5 were prepared and subjected to the same reaction sequence
as for the preparation of 4 from 1. As outlined in Scheme 2, successive treatment of 5
with BuLi and nitriles afforded the corresponding imine precursors 6. When
compounds 6 were subjected to the treatment with a catalytic amount of TsOH · H2O
in refluxing CHCl3, the desired cyclization products 7 were obtained. However, the
yields of 7 were much lower than those of 4. This may be ascribed to the lability of 7
toward the reaction conditions due to the strained 3-substituted 1-alkoxy-1H-isoindole
structure compared to the 1-substituted 3-alkoxy-1H-isoindole structure of 4.
Scheme 2
Conclusions. – It has been demonstrated that the reaction of 2-(dialkoxymethyl)-
phenyllithium compounds with nitriles, followed by acid-catalyzed cyclization of the
resulting [2-(dialkoxymethyl)phenyl]methanimines, provides a reliable two-step meth-

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od for the preparation of 1-substituted 3-alkoxy-1H-isoindoles from 1-bromo-2-
(dialkoxymethyl)benzenes. The presented protocol has advantages over previous
methods in that starting materials are readily available and that the operations with
inexpensive reagents are very simple. We are currently evaluating further utilizations of
2-(dialkoxymethyl)phenyllithiums for the preparation of other heterocyclic systems.
Experimental Part
General. All org. solvents used in this study were dried over appropriate drying agents and distilled
prior to use. TLC: Merck silica gel 60 PF254. Column chromatography (CC): Wako Gel C-200E or Kanto
Silica Gel 60 N. M.p.: Laboratory Devices MEL-TEMP II melting-point apparatus; uncorrected. IR
Spectra: PerkinElmer Spectrum65 FT-IR spectrophotometer; ˜n in cmꢀ1. NMR Spectra: Bruker Biospin
AVANCE II 600 FT NMR spectrometer or JEOL ECP500 FT NMR spectrometer (at 600 and 500 MHz,
resp., for 1H, and at 150 and 125 MHz, resp., for 13C), in CDCl3; d in ppm rel. to Me4Si as internal
standard, J in Hz. HR-MS (DART, pos.): Thermo Scientific Exactive spectrometer; in m/z.
1-(2-Bromo-5-methoxyphenyl)ethanone [8], 1-bromo-2-(dimethoxymethyl)benzene (1b) [9], and 1-
bromo-4-chloro-2-(diethoxymethyl)benzene (1c) [6a] were prepared according to the appropriate
reported procedures. BuLi was supplied by Asia Lithium Corporation. All other chemicals used were
commercially available.
1-Bromo-4-methoxy-2-(diethoxymethyl)benzene (1d) [10] was prepared from 2-bromo-5-methoxy-
benzaldehyde and HC(OEt)3 as described in [9] for 1b. Yield: 82%. Pale-yellow liquid. Rf (CH2Cl2/hexane
2 :3) 0.43. IR (neat): 1060. 1H-NMR (500 MHz): 1.25 (t, J ¼ 6.9, 6 H); 3.56 –3.62 (m, 2 H); 3.66–3.72 (m,
2 H); 3.80 (s, 3 H); 5.60 (s, 1 H); 6.75 (dd, J ¼ 8.4, 3.1, 1 H); 7.21 (d, J ¼ 3.1, 1 H); 7.42 (d, J¼ 8.4, 1 H).
1-Bromo-2-(diethoxymethyl)-4,5-dimethoxybenzene (1e) [11] was prepared from 2-bromo-4,5-
dimethoxybenzaldehyde and HC(OEt)3 as described in [9] for 1b. Yield: 96%.Colorless liquid. Rf
(CH2Cl2/hexane 1:3) 0.39. IR (neat): 1603, 1163, 1060. 1H-NMR (500 MHz):1.25 (t, J ¼ 6.9, 6 H); 3.54 –
3.60 (m, 2 H); 3.69 – 3.73 (m, 2 H); 3.87 (s, 3 H); 3.89 (s, 3 H); 5.59 (s, 1 H); 6.99 (s, 1 H); 7.16 (s, 1 H).
1-Bromo-2-(1,1-diethoxyethyl)benzene (5a) was prepared from 1-(2-bromophenyl)ethanone and
HC(OEt)3 as described in [9] for 1b. Yield: 85%. Colorless liquid. Rf (CH2Cl2/hexane 1:5) 0.40. IR
(neat): 1165, 1057. 1H-NMR (500 MHz): 1.25 (t, J ¼ 6.9, 6 H); 1.70 (s, 3 H); 3.33 – 3.39 (m, 2 H); 3.47 –
3.53 (m, 2 H); 7.11 (td, J ¼ 7.6, 1.5, 1 H); 7.30 (td, J ¼ 7.6, 1.5, 1 H); 7.59 (dd, J ¼ 7.6, 1.5, 1 H); 7.85 (dd,
J ¼ 7.6, 1.5, 1 H). Anal. calc. for C12H17BrO2 (273.17): C 52.76, H 6.27; found: C 52.73, H 6.37.
1-Bromo-2-(1,1-diethoxyethyl)-4-methoxybenzene (5b) was prepared from 1-(2-bromo-5-methoxy-
phenyl)ethanone [8] and HC(OEt)3 as described in [9] for 1b. Yield: 79%. Colorless liquid. Rf (CH2Cl2/
hexane 1:3) 0.26. IR (neat): 1164, 1055. 1H-NMR (500 MHz): 1.25 (t, J ¼ 7.6, 6 H); 1.69 (s, 3 H); 3.33 –
3.39 (m, 2 H); 3.46 – 3.52 (m, 2 H); 3.80 (s, 3 H); 6.68 (dd, J ¼ 8.4, 3.1, 1 H); 7.45 (d, J ¼ 3.1, 1 H); 7.47 (d,
J ¼ 8.4, 1 H). Anal. calc. for C13H19BrO3 (303.19): C 51.50, H 6.32; found: C 51.49, H 6.35.
1-(3-Chlorophenyl)-1-[2-(diethoxymethyl)phenyl]methanimine (2b): Representative Procedure. To a
stirred soln. of 1-bromo-2-(diethoxymethyl)benzene (1a; 0.52 g, 2.0 mmol) in THF (4 ml) at ꢀ 788 was
added BuLi (1.6m in hexane, 2.0 mmol). After 15 min, a soln. of 3-ClꢀC6H4CN (0.28 g, 2.0 mmol) in THF
(2 ml) was added, and the temp. was gradually raised to ꢀ 408. Stirring was continued for 1 h before H2O
(15 ml) was added. The mixture was warmed to r.t. and extracted with AcOEt (3 ꢂ 10 ml). The combined
extracts were washed with brine (10 ml), dried (Na2SO4), and concentrated by evaporation. The residue
was purified by CC (neutral SiO2) to give 2b (0.56 g, 87%). Pale-yellow oil. Rf (AcOEt/hexane 1:10)
0.18. IR (neat): 3261, 1610, 1061. 1H-NMR (500 MHz): 1.12 (t, J ¼ 7.6, 6 H); 3.33 – 3.39 (m, 2 H); 3.52 (m,
2 H); 5.24 (br. s, 1 H); 7.18 (d, J ¼ 7.6, 1 H); 7.32 (t, J ¼ 7.6, 1 H); 7.39 (d, J ¼ 7.6, 6.9, 1 H); 7.43 (d, J ¼ 7.6,
1 H); 7.48 (t, J ¼ 7.6, 1 H); 7.54 (d, J ¼ 6.9, 1 H); 7.736 (s, 1 H); 7.743 (d, J ¼ 7.6, 1 H); 9.80 (br. s, 1 H).
Anal. calc. for C18H20ClNO2 (317.81): C 68.03, H 6.34, N 4.41; found: C 67.85, H 6.40, N 4.20.
1-[2-(Diethoxymethyl)phenyl]-1-phenylmethanimine (2a). Pale-yellow oil. Rf (AcOEt/hexane 1:3)
0.36. IR (neat): 3260, 1607, 1062. 1H-NMR (500 MHz): 1.11 (t, J ¼ 6.9, 6 H); 3.31 – 3.37 (m, 2 H); 3.52 –
3.58 (m, 2 H); 5.25 (br. s, 1 H); 7.21 (d, J ¼ 6.9, 1 H); 7.36 – 7.40 (m, 3 H); 7.44 – 7.48 (m, 2 H); 7.64 – 7.72

Helvetica Chimica Acta – Vol. 98 (2015)
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(br., 2 H); 7.75 (d, J ¼ 7.6, 1 H); 9.67 (br. s, 1 H). Anal. calc. for C18H21NO2 (283.36): C 76.29, H 7.47, N
4.94; found: C 76.21, H 7.54, N 4.91.
1-(4-Chlorophenyl)-1-[2-(diethoxymethyl)phenyl]methanimine (2c). Yellow oil. Rf (AcOEt/hexane
1
1:5) 0.31. IR (neat): 3263, 1609, 1062. H-NMR (500 MHz): 1.12 (t, J ¼ 6.9, 6 H); 3.32 – 3.38 (m, 2 H);
3.52 – 3.58 (m, 2 H); 5.22 (br. s, 1 H); 7.17 (d, J ¼ 7.6, 1 H); 7.35 (d, J ¼ 8.4, 2 H); 7.38 (ddd, J ¼ 7.6, 6.9, 1.5,
1 H); 7.47 (td, J ¼ 7.6, 1.5, 1 H); 7.65 (br., 2 H); 7.74 (d, J ¼ 6.9, 1 H); 9.69 (br., 1 H). Anal. calc. for
C18H20ClNO2 (317.81): C 68.03, H 6.34, N 4.41; found: C 67.90, H 6.18, N 4.28.
1-[2-(Diethoxymethyl)phenyl]-1-(4-methoxyphenyl)methanimine (2d). Yellow oil. Rf (AcOEt/hex-
ane 1:2) 0.34. IR (neat): 3262, 1604, 1254, 1061. 1H-NMR (600 MHz): 1.12 (t, J ¼ 7.1, 6 H); 3.33 – 3.38 (m,
2 H); 3.52 – 3.57 (m, 2 H); 3.84 (s, 3 H); 5.27 (s, 1 H); 6.89 (d, J ¼ 8.9, 2 H); 7.20 (d, J ¼ 7.4, 1 H); 7.36 (td,
J ¼ 7.4, 1.1, 1 H); 7.45 (td, J ¼ 7.4, 1.1, 1 H); 7.64 (br. d, J ¼ 8.9, 2 H); 7.74 (d, J ¼ 7.4, 1 H); 9.42 (br., 1 H).
Anal. calc. for C19H23NO3 (313.39): C 72.82, H 7.40, N 4.47; found: C 72.71, H 7.41, N 4.36.
1-[2-(Diethoxymethyl)phenyl]-1-(1,1-dimethylethyl)methanimine (2e). Yellow oil. Rf (AcOEt/hex-
ane 1:3) 0.40. IR (neat): 3260, 1615, 1064. 1H-NMR (600 MHz): 1.23 (t, J ¼ 7.0, 6 H); 1.26 (s, 9 H); 3.44 –
3.49 (m, 2 H); 3.63 – 3.68 (m, 2 H); 5.21 (s, 1 H); 7.12 (dd, J ¼ 7.6, 1.1, 1 H); 7.29 (td, J ¼ 7.6, 1.1, 1 H); 7.37
(td, J ¼ 7.6, 1.1, 1 H); 7.70 (dd, J ¼ 7.6, 1.1, 1 H); 9.42 (br., 1 H). Anal. calc. for C16H25NO2 (263.38): C
72.96, H 9.57, N 5.32; found: C 72.90, H 9.60, N 5.27.
1-[2-(Dimethoxymethyl)phenyl]-1-phenylmethanimine (2f). Yellow oil. Rf (AcOEt/hexane 1:1)
0.43. IR (neat): 3260, 1607, 1088. 1H-NMR (500 MHz): 3.22 (s, 6 H); 5.15 (s, 1 H); 7.24 (d, J ¼ 8.4, 1 H);
7.38 – 7.41 (m, 3 H); 7.44 – 7.49 (m, 2 H); 7.66 (d, J ¼ 7.6, 2 H); 7.70 (d, J ¼ 7.6, 1 H); 9.52 (br., 1 H). Anal.
calc. for C16H17NO2 (255.31): C 75.27, H 6.71, N 5.49; found: C 75.15, H 6.73, N 5.44.
1-(3-Chlorophenyl)-1-[2-(dimethoxymethyl)phenyl]methanimine (2g). Yellow oil. Rf (AcOEt/hex-
ane 1:2) 0.37. IR (neat): 3258, 1610, 1087. 1H-NMR (500 MHz): 3.23 (s, 6 H); 5.11 (br. s, 1 H); 7.21 (br.,
1 H); 7.32 (dd, J ¼ 8.6, 7.6, 1 H); 7.41 (t, J ¼ 7.6, 1 H); 7.43 (d, J ¼ 7.6, 1 H); 7.49 (t, J ¼ 7.6, 1 H); 7.53 (br.,
1 H); 7.70 (d, J ¼ 7.6, 1 H); 7.76 (br., 1 H); 9.47 (br., 1 H). Anal. calc. for C16H16ClNO2 (289.76): C 66.32,
H 5.57, N 4.83; found: C 66.13, H 5.54, N 4.90.
1-[4-Chloro-2-(diethoxymethyl)phenyl]-1-phenylmethanimine (2h). Pale-yellow oil. Rf (AcOEt/
hexane 1:5) 0.32. IR (neat): 3262, 1605, 1059. 1H-NMR (500 MHz): 1.11 (t, J ¼ 6.9, 6 H); 3.32 – 3.38 (m,
2 H); 3.50 – 3.56 (m, 2 H); 5.22 (br., 1 H); 7.16 (br., 1 H); 7.35 (dd, J ¼ 8.4, 2.3. 1 H); 7.39 (t, J ¼ 8.4, 7.6,
2 H); 7.46 (d, J ¼ 7.6, 1 H); 7.47 (t, J ¼ 7.6, 1 H); 7.67 (br. d, J ¼ 8.4, 1 H); 7.74 (d, J ¼ 2.3, 1 H); 9.68 (br.,
1 H). Anal. calc. for C18H20ClNO2 (317.81): C 68.03, H 6.34, N 4.41; found: C 67.75, H 6.30, N 4.21.
1-[4-Chloro-2-(diethoxymethyl)phenyl]-1-(3-chlorophenyl)methanimine (2i). Yellow oil. Rf
(AcOEt/hexane 1:5) 0.33. IR (neat): 3262, 1606, 1060. 1H-NMR (500 MHz): 1.12 (t, J ¼ 6.9, 6 H);
3.33 – 3.40 (m, 2 H); 3.49 – 3.57 (m, 2 H); 5.18 (br., 1 H); 7.13 (br., 1 H); 7.32 (dd, J ¼ 8.4, 7.6, 1 H); 7.36
(dd, J ¼ 8.4, 2.3, 1 H); 7.44 (d, J ¼ 7.6, 1 H); 7.53 (br., 1 H); 7.73 (d, J ¼ 2.3, 1 H); 7.75 (br., 1 H); 9.80 (br.,
1 H). Anal. calc. for C18H19Cl2NO2 (352.26): C 61.37, H 5.44, N 3.98; found: C 61.15, H 5.47, N 3.90.
1-[2-(Diethoxymethyl)-4-methoxyphenyl]-1-phenylmethanimine (2j). Pale-yellow oil. Rf (AcOEt/
hexane 1:3) 0.32. IR (neat): 3262, 1607, 1061. 1H-NMR (500 MHz): 1.13 (t, J ¼ 7.6, 6 H); 3.32 – 3.38 (m,
2 H); 3.52 – 3.59 (m, 2 H); 3.87 (s, 3 H); 5.24 (br. s, 1 H); 6.89 (dd, J ¼ 8.4, 3.1, 1 H); 7.14 (d, J ¼ 8.4, 1 H);
7.28 (d, J ¼ 3.1, 1 H); 7.38 (t, J ¼ 7.6, 2 H); 7.45 (t, J ¼ 7.6, 1 H); 7.67 (br. d, J ¼ 7.6, 2 H); 9.69 (br., 1 H).
Anal. calc. for C19H23NO3 (313.39): C 72.82, H 7.40, N 4.47; found: C 72.60, H 7.45, N 4.43.
1-(3-Chlorophenyl)-1-[2-(diethoxymethyl)-4-methoxyphenyl]methanimine (2k). Pale-yellow oil. Rf
(AcOEt/hexane 1:4) 0.39. IR (neat): 3262, 1607, 1061. 1H-NMR (500 MHz): 1.14 (t, J ¼ 7.6, 6 H); 3.39 –
4.00 (m, 2 H); 3.53 – 3.59 (m, 2 H); 3.87 (s, 3 H); 5.21 (br., 1 H); 6.89 (dd, J ¼ 8.4, 3.1, 1 H); 7.10 (d, J ¼
8.4, 1 H); 7.28 (d, J ¼ 3.1, 1 H); 7.31 (dd, J ¼ 8.4, 7.6, 1 H); 7.42 (dd, J ¼ 8.4, 2.3, 1 H); 7.54 (br., 1 H); 7.71
(br., 1 H); 9.78 (br., 1 H). Anal. calc. for C19H22ClNO3 (347.84): C 65.61, H 6.38, N 4.03; found: C 65.70,
H 6.29, N 3.92.
1-[2-(Diethoxymethyl)-4,5-dimethoxyphenyl]-1-phenylmethanimine (2l). Yellow oil. Rf (AcOEt/
hexane 1:2) 0.32. IR (neat): 3262, 1603, 1058. 1H-NMR (500 MHz): 1.14 (t, J ¼ 6.9, 6 H); 3.30 – 3.36 (m,
2 H); 3.52 – 3.58 (m, 2 H); 3.90 (s, 3 H); 3.96 (s, 3 H); 5.17 (br. s, 1 H); 6.69 (br. s, 1 H); 7.25 (s, 1 H); 7.40
(dd, J ¼ 8.4, 7.6, 2 H); 7.47 (t, J ¼ 7.6, 1 H); 7.70 (br., 2 H); 9.71 (br., 1 H). Anal. calc. for C20H25NO4
(343.42): C 69.95, H 7.34, N 4.08; found: C 69.98, H 7.31, N 4.03.

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Helvetica Chimica Acta – Vol. 98 (2015)
1-(3-Chlorophenyl)-1-[2-(diethoxymethyl)-4,5-dimethoxyphenyl]methanimine (2m). Yellow oil. Rf
(AcOEt/hexane 2 :5) 0.30. IR (neat): 3259, 1604, 1059. 1H-NMR (500 MHz): 1.15 (t, J ¼ 7.6, 6 H); 3.32 –
3.38 (m, 2 H); 3.53 – 3.59 (m, 2 H); 3.83 (s, 3 H); 3.96 (s, 3 H); 5.15 (br., 1 H); 6.64 (br., 1 H); 7.25 (s,
1 H); 7.32 (dd, J ¼ 8.4, 7.6, 1 H); 7.44 (d, J ¼ 7.6, 1 H); 7.56 (br., 1 H); 7.76 (br., 1 H); 9.79 (br., 1 H). Anal.
calc. for C20H24ClNO4 (377.86): C 63.57, H 6.40, N 3.71; found: C 63.59, H 6.42, N 3.44.
1-(4-Chlorophenyl)-1-[2-(diethoxymethyl)-4,5-dimethoxyphenyl]methanimine (2n). Yellow oil. Rf
(AcOEt/hexane 1:2) 0.31. IR (neat): 3262, 1605, 1059. 1H-NMR (500 MHz): 1.14 (t, J ¼ 6.9, 6 H);
3.32 – 3.38 (m, 2 H); 3.53 – 3.59 (m, 2 H); 3.82 (s, 3 H); 3.95 (s, 3 H); 5.46 (br. s, 1 H); 6.63 (br. s, 1 H); 7.24
(s, 1 H); 7.36 (d, J ¼ 8.4, 2 H); 7.66 (br. d, J ¼ 8.4, 2 H); 9.71 (br., 1 H). Anal. calc. for C20H24ClNO4
(377.86): C 63.57, H 6.40, N 3.71; found: C 63.29, H 6.21, N 3.80.
1-(4-Chlorophenyl)-1-[2-(1,1-diethoxyethyl)phenyl]methanimine (6a).White solid. M.p. 76 – 778
(hexane). IR (KBr): 3262, 1610, 1051. 1H-NMR (500 MHz): 0.93 (t, J ¼ 7.6, 6 H); 1.45 (s, 3 H); 3.26
(q, J ¼ 7.6, 4 H); 7.08 (d, J ¼ 6.9, 1 H); 7.30 – 7.34 (m, 3 H); 7.41 (td, J ¼ 6.9, 1.5, 1 H); 7.54 (d, J ¼ 7.6, 1 H);
7.60 (br. d, J ¼ 6.9, 2 H); 9.05 (br., 1 H). Anal. calc. for C19H22ClNO2 (331.84): C 68.77, H 6.68, N 4.22;
found: C 68.66, H 6.67, N 4.16.
1-[2-(1,1-Diethoxyethyl)-4-methoxyphenyl]-1-phenylmethanimine (6b). Light-brown oil. Rf (AcOEt/
1
hexane 1:3) 0.41. IR (neat): 3261, 1607, 1059. H-NMR (500 MHz): 0.94 (t, J ¼ 6.9, 6 H); 1.41 (s, 3 H);
3.23 – 3.32 (m, 4 H); 3.86 (s, 3 H); 6.87 (dd, J ¼ 8.4, 3.1, 1 H); 7.06 (d, J ¼ 8.4, 1 H); 7.08 (d, J ¼ 3.1, 1 H);
7.33 (dd, J ¼ 7.6, 6.9, 2 H); 7.37 (t, J ¼ 7.6, 1 H); 7.63 (br. d, J ¼ 6.9, 2 H); 9.16 (br., 1 H). Anal. calc. for
C20H25NO3 (327.42): C 73.37, H 7.70, N 4.28; found: C 73.08, H 7.75, N 4.19.
1-(3-Chlorophenyl)-1-[2-(1,1-diethoxyethyl)-4-methoxyphenyl]methanimine (6c). Pale-yellow oil. Rf
(AcOEt/hexane 1:4) 0.30. IR (neat): 3264, 1608, 1060. 1H-NMR (500 MHz): 0.95 (t, J ¼ 6.9, 6 H); 1.43 (s,
3 H); 3.23 – 3.31 (m, 4 H); 3.86 (s, 3 H); 6.87 (dd, J ¼ 8.4, 2.3, 1 H); 7.02 (d, J ¼ 8.4, 1 H); 7.08 (d, J ¼ 2.3,
1 H); 7.26 (t, J ¼ 7.6, 1 H); 7.35 (dd, J ¼ 7.6, 1.5, 1 H); 7.53 (br. d, J ¼ 7.6, 1 H); 7.65 (br. s, 1 H); 9.17 (br.,
1 H). Anal. calc. for C20H24ClNO3 (361.86): C 66.38, H 6.69, N 3.87; found: C 66.16, H 6.80, N 3.86.
1-(3-Chlorophenyl)-3-ethoxy-1H-isoindole (4b). Representative Procedure. A soln. of 2b (0.19 g,
0.61 mmol) in CHCl3 (4 ml) containing TsOH · H2O (12 mg, 0.061 mmol) was heated at reflux temp. for
8 h. The cooled mixture was diluted with CH2Cl2 (25 ml) and washed with sat. aq. NaHCO3 (10 ml). The
org. layer was dried (Na2SO4) and concentrated by evaporation. The residue was purified by CC (SiO2;
AcOEt/hexane 1:4) to afford 4b (0.13 g, 76%). Pale-yellow solid. M.p. 99 – 1018 (hexane/Et2O). IR
1
(KBr): 1621, 1598, 1575, 1345. H-NMR (500 MHz): 1.50 (t, J ¼ 6.9, 3 H); 4.53 – 4.60 (m, 2 H); 5.66 (s,
1 H); 7.147 (d, J ¼ 6.9, 1 H); 7.153 (d, J ¼ 1.5, 1 H); 7.21 – 7.25 (m, 2 H); 7.32 (dd, J ¼ 8.4, 2.3, 1 H); 7.37 –
7.42 (m, 2 H); 7.61 – 7.62 (m, 1 H). 13C-NMR (125 MHz): 14.5; 64.3; 71.8; 120.8; 122.8; 125.5; 127.1; 127.6;
127.7; 129.6; 129.8; 132.4; 134.3; 141.3; 153.3; 170.3. HR-MS: 272.0831 ([M þ H]þ, C16H15ClNOþ; calc.
272.0842). Anal. calc. for C16H14ClNO (271.74): C 70.72, H 5.19, N 5.15; found: C 70.48, H 5.49, N 5.10.
3-Ethoxy-1-phenyl-1H-isoindole (4a) [12a]. Pale-yellow solid. M.p. 91 – 928 (hexane; [12a]: 88 – 898).
IR (KBr): 1618, 1599, 1570, 1343. 1H-NMR (500 MHz): 1.49 (t, J ¼ 6.9, 3 H); 4.51 – 4.62 (m, 2 H); 5.70 (s,
1 H); 7.20 (dd, J ¼ 6.9, 1.5, 2 H); 7.25 (d, J ¼ 6.9, 1 H); 7.28 – 7.33 (m, 3 H); 7.34 – 7.39 (m, 2 H); 7.60 (dd,
J ¼ 6.9, 2.3, 1 H). 13C-NMR (125 MHz): 14.6; 64.1; 72.4; 120.6; 122.8; 127.1; 127.4; 127.4; 128.6; 129.4;
132.5; 139.2; 154.0; 169.9.
1-(4-Chlorophenyl)-3-ethoxy-1H-isoindole (4c). Pale-yellow solid. M.p. 103 – 1048 (hexane/Et2O;
[2]: 100 – 1018). IR (KBr): 1620, 1599, 1570, 1346. 1H-NMR (500 MHz): 1.49 (t, J ¼ 6.9, 3 H); 4.50 – 4.60
(m, 2 H); 5.66 (s, 1 H); 7.14 (d, J ¼ 8.4, 2 H); 7.26 (d, J ¼ 8.4, 2 H); 7.28 (dd, J ¼ 8.4, 2.3, 1 H); 7.36 – 7.41
(m, 2 H); 7.61 (dd, J ¼ 7.6, 2.3, 1 H). 13C-NMR (125 MHz): 14.5; 64.2; 71.7; 120.7; 122.7; 127.6; 128.5;
128.7; 129.6; 132.5; 133.1; 137.8; 153.6; 170.2.
3-Ethoxy-1-(4-methoxyphenyl)-1H-isoindole (4d) [13]. Pale-yellow solid. M.p. 61–638 (hexane/Et2O;
[13]: 64–658). IR (KBr): 1621, 1599, 1571, 1345. 1H-NMR (600 MHz): 1.48 (t, J¼ 7.1, 3 H); 3.77 (s, 3 H);
4.50–4.60 (m, 2 H); 5.66 (s, 1 H); 6.83 (d, J¼ 8.6, 2 H); 7.11 (d, J¼ 8.6, 2 H); 7.31 (dd, J¼ 8.4, 1.7, 1 H);
7. 35 – 7.39 ( m, 2 H); 7.60 (dd, J¼ 8.4, 1.7, 1 H). 13C-NMR (150 MHz): 14.6; 55.3; 64.1; 72.0; 114.0; 120.6;
122.9; 127.3; 128.3; 129.5; 131.3; 132.6; 154.4; 159.0; 169.7. HR-MS: 268.1329 ([M þ H]þ, C17H18NO2þ ; calc.
268.1337). Anal. calc. for C17H17NO2 (267.32): C 76.38, H 6.41, N 5.24; found: C 76.28, H 6.44, N 5.10.
1-(1,1-Dimethylethyl)-3-ethoxy-1H-isoindole (4e). Yellow oil. Rf (AcOEt/hexane 1:12) 0.39. IR
1
(neat): 1626, 1599, 1577, 1344. H-NMR (500 MHz): 1.01 (s, 9 H); 1.46 (t, J ¼ 6.9, 3 H); 4.41 – 4.45 (m,

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including s at 4.22, 2 H); 4.53 – 4.60 (m, 1 H); 7.34 – 7.37 (m, 2 H); 7.51 – 7.58 (m, 2 H). 13C-NMR
(125 MHz): 14.6; 27.1; 35.3; 63.4; 77.8; 120.2; 123.8; 126.9; 128.2; 133.8; 152.2; 168.4. HR-MS: 218.1535
([M þ H]þ, C14H20NOþ; calc. 218.1545). Anal. calc. for C14H19NO (217.31): C 77.38, H 8.81, N 6.45; found:
C 77.28, H 8.52, N 6.42.
3-Methoxy-1-phenyl-1H-isoindole (4f) [12]. Pale-yellow solid. M.p. 112 – 1148 (hexane; [12b]: 111 –
1138). IR (KBr): 1623, 1600, 1574, 1372. 1H-NMR (500 MHz): 4.15 (s, 3 H); 5.71 (s, 1 H); 7.20 (dd, J ¼
8.4, 2.3, 2 H); 7.25 (t, J ¼ 7.6, 1 H); 7.29 – 7.33 (m, 3 H); 7.35 – 7.40 (m, 2 H); 7.59 (dd, J ¼ 8.4, 2.3, 1 H).
13C-NMR (125 MHz): 55.5; 72.4; 120.6; 122.9; 127.2; 127.4; 127.5; 128.6; 129.5; 132.2; 139.0; 154.1; 170.6.
1-(3-Chlorophenyl)-3-methoxy-1H-isoindole (4g). Pale-yellow solid. M.p. 85 – 868 (hexane/CH2Cl2).
IR (KBr): 1623, 1599, 1577, 1373. 1H-NMR (500 MHz): 4.16 (s, 3 H); 5.67 (s, 1 H); 7.15 (br. s, 2 H); 7.24 –
7.27 (m, 2 H); 7.33 (dd, J ¼ 8.4, 3.1, 1 H); 7.37 – 7.42 (m, 2 H); 7.59 (d, J ¼ 8.4, 1 H). 13C-NMR (125 MHz):
55.6; 71.7; 120.7; 122.8; 125.5; 127.1; 127.7; 127.7; 129.7; 129.9; 132.1; 134.4; 141.2; 153.4; 170.9. HR-MS:
258.0675 ([M þ H]þ, C15H13ClNOþ; calc. 258.0685). Anal. calc. for C15H12ClNO (257.71): C 69.91, H 4.69,
N 5.43; found: C 69.80, H 4.40, N 5.30.
5-Chloro-3-ethoxy-1-phenyl-1H-isoindole (4h). Pale-yellow solid. M.p. 90 – 928 (hexane). IR (KBr):
1618, 1596, 1571, 1336. 1H-NMR (500 MHz): 1.48 (t, J ¼ 6.9, 3 H); 4.50 – 4.60 (m, 2 H); 5.68 (s, 1 H); 7.17
(dd, J ¼ 8.4, 1.5, 2 H); 7.22 – 7.26 (m, 2 H); 7.28 – 7.33 (m, 3 H); 7.58 (d, J ¼ 1.5, 1 H). 13C-NMR
(125 MHz): 14.5; 64.4; 72.3; 120.9; 123.9; 127.1; 127.7; 128.7; 129.6; 133.6; 134.2; 138.5; 152.3; 168.8. HR-
MS: 272.0836 ([M þ H]þ, C16H15ClNOþ; calc. 272.0842). Anal. calc. for C16H14ClNO (271.74): C 70.72, H
5.19, N 5.15; found: C 70.65, H 5.17, N 5.09.
5-Chloro-1-(3-chlorophenyl)-3-ethoxy-1H-isoindole (4i). Pale-yellow solid. M.p. 97 – 1008 (hexane/
1
CH2Cl2). IR (KBr): 1618, 1596, 1575, 1338. H-NMR (500 MHz): 1.49 (t, J ¼ 7.6, 3 H); 4.50 – 4.60 (m,
2 H); 5.64 (s, 1 H); 7.11 (dd, J ¼ 6.9, 1.5, 1 H); 7.13 (br. s, 1 H); 7.22 – 7.24 (m, 3 H); 7.35 (dd, J ¼ 8.4, 1.5,
1 H); 7.59 (d, J ¼ 1.5, 1 H). 13C-NMR (125 MHz): 14.5; 64.6; 71.6; 121.1; 123.8; 125.4; 127.1; 127.9; 129.8;
123.0; 133.9; 134.2; 134.5; 140.7; 151.6; 169.1. HR-MS: 306.0446 ([M þ H]þ, C16H14Cl2NOþ; calc.
306.0452). Anal. calc. for C16H13Cl2NO (306.19): C 62.76, H 4.28, N 4.57; found: C 62.54, H 4.05, N 4.39.
3-Ethoxy-5-methoxy-1-phenyl-1H-isoindole (4j). White solid. M.p. 110 – 1118 (hexane/CH2Cl2). IR
1
(KBr): 1624, 1575, 1345. H-NMR (500 MHz): 1.49 (t, J ¼ 7.6, 3 H); 3.85 (s, 3 H); 4.50 – 4.61 (m, 2 H);
5.64 (s, 1 H); 6.93 (dd, J ¼ 8.4, 2.3, 1 H); 7.08 (d, J ¼ 2.3, 1 H); 7.17 – 7.20 (m, 3 H); 7.23 (t, J ¼ 7.6, 1 H);
7.29 (t, J ¼ 7.6, 2 H). 13C-NMR (125 MHz): 14.6; 55.6; 64.2; 71.9; 104.2; 117.2; 123.5; 127.1; 127.4; 128.5;
133.9; 139.5; 146.5; 159.7; 169.5. HR-MS: 268.1329 ([M þ H]þ, C17H18NO2þ ; calc. 268.1337). Anal. calc.
for C17H17NO2 (267.32): C 76.38, H 6.41, N 5.24; found: C 76.18, H 6.38, N 5.20.
1-(3-Chlorophenyl)-3-ethoxy-5-methoxy-1H-isoindole (4k). Pale-yellow solid. M.p. 89 – 908 (hexane/
Et2O). IR (KBr): 1626, 1577, 1339. 1H-NMR (500 MHz): 1.50 (t, J ¼ 6.9, 3 H); 3.86 (s, 3 H); 4.50–4.60 (m,
2 H); 5.60 (s, 1 H); 6.94 (dd, J¼ 7.6, 2.3, 1 H); 7.09 (d, J ¼ 2.3, 1 H); 7.12–7.14 (m, 2 H); 7.18 (d, J¼ 8.4,
1 H); 7.20–7.25 (m, 2 H). 13C-NMR (125 MHz): 14.5; 55.7; 64.3; 71.2; 104.4; 117.4; 123.4; 125.4; 127.1; 127.6;
129.8; 133.9; 134.3; 141.7; 145.7; 159.9; 169.9. HR-MS: 302.0942 ([M þ H]þ, C17H17ClNO2þ ; calc. 302.0948).
Anal. calc. for C17H16ClNO2 (301.77): C 67.66, H 5.34, N 4.64; found: C 67.43, H 5.28, N 4.55.
3-Ethoxy-5,6-dimethoxy-1-phenyl-1H-isoindole (4l). Pale-yellow solid. M.p. 113 – 1148 (hexane/
CH2Cl2). IR (KBr): 1623, 1602, 1569, 1342. 1H-NMR (500 MHz): 1.48 (t, J ¼ 7.6, 3 H); 3.83 (s, 3 H); 3.94
(s, 3 H); 4.48 – 4.59 (m, 2 H); 5.60 (s, 1 H); 6.79 (s, 1 H); 7.07 (s, 1 H); 7.18 (d, J ¼ 6.9, 2 H); 7.25 (t, J ¼ 7.6,
1 H); 7.30 (dd, J ¼ 7.6, 6.9, 2 H). 13C-NMR (125 MHz): 14.6; 56.1; 56.2; 64.1; 72.3; 102.6; 105.4; 124.9;
127.3; 127.4; 128.6; 139.5; 147.7; 149.2; 151.1; 169.7. HR-MS: 298.1438 ([M þ H]þ, C18H20NO3þ ; calc.
298.1443). Anal. calc. for C18H19NO3 (297.35): C 72.71, H 6.44, N 4.71; found: C 72.77, H 6.59, N 4.60.
1-(3-Chlorophenyl)-3-ethoxy-5,6-dimethoxy-1H-isoindole (4m). White solid. M.p. 102 – 1058 (hex-
ane/CH2Cl2). IR (KBr): 1622, 1601, 1567, 1340. 1H-NMR (500 MHz): 1.49 (t, J ¼ 6.9, 3 H); 3.85 (s, 3 H);
3.95 (s, 3 H); 4.50 – 4.57 (m, 2 H); 5.55 (s, 1 H); 6.77 (s, 1 H); 7.08 (s, 1 H); 7.11 (dd, J ¼ 7.6, 1.5, 1 H); 7.13
(br. s, 1 H); 7.22 – 7.25 (m, 2 H). 13C-NMR (125 MHz): 14.6; 56.1; 56.2; 64.3; 71.6; 102.7; 105.3; 124.8;
125.6; 127.3; 127.6; 129.9; 134.4; 141.7; 147.0; 149.4; 151.3; 170.1. HR-MS: 332.1044 ([M þ H]þ,
C18H19ClNOþ3 ; calc. 332.1053). Anal. calc. for C18H18ClNO3 (331.79): C 65.16, H 5.47, N 4.22; found: C
64.99, H 5.46, N 4.27.
1-(4-Chlorophenyl)-3-ethoxy-5,6-dimethoxy-1H-isoindole (4n). Pale-yellow solid. M.p. 131 – 1328
1
(hexane/CH2Cl2). IR (KBr): 1622, 1601, 1567, 1339. H-NMR (500 MHz): 1.48 (t, J ¼ 6.9, 3 H); 3.84 (s,

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3 H); 3.95 (s, 3 H); 4.47 – 4.57 (m, 2 H); 5.56 (s, 1 H); 6.75 (s, 1 H); 7.07 (s, 1 H); 7.12 (d, J ¼ 8.4, 2 H); 7.27
(d, J ¼ 8.4, 2 H). 13C-NMR (125 MHz): 14.6; 56.1; 56.2; 64.2; 71.5; 102.6; 105.3; 124.8; 128.6; 128.8; 133.1;
138.1; 147.2; 149.3; 151.3; 169.9. HR-MS: 332.1045 ([M þ H]þ, C18H19ClNO3þ ; calc. 332.1053). Anal. calc.
for C18H18ClNO3 (331.79): C 65.16, H 5.47, N 4.22; found: C 65.27, H 5.56, N 4.07.
3-(4-Chlorophenyl)-1-ethoxy-1-methyl-1H-isoindole (7a). Pale-yellow solid. M.p. 85 – 868 (hexane/
CH2Cl2). IR (KBr): 1596, 1138. 1H-NMR (500 MHz): 1.13 (t, J ¼ 7.6, 3 H); 1.72 (s, 3 H); 2.92 – 2.99 (m,
1 H); 3.21 – 3.28 (m, 1 H); 7.42 – 7.48 (m, 2 H); 7.51 (d, J ¼ 8.4, 2 H); 7.59 (d, J ¼ 6.9, 1 H); 7.66 (d, J ¼ 6.9,
1 H); 7.93 (d, J ¼ 8.4, 2 H). 13C-NMR (125 MHz): 15.5; 25.2; 59.2; 103.0; 122.7; 122.8; 128.9; 129.0; 129.5;
129.7; 132.3; 136.5; 136.8; 153.3; 168.8. HR-MS: 286.0992 ([M þ H]þ, C17H17ClNOþ; calc. 286.0998).
Anal. calc. for C17H16ClNO (285.77): C 71.45, H 5.64, N 4.90; found: C 71.31, H 5.60, N 4.91.
1-Ethoxy-6-methoxy-1-methyl-3-phenyl-1H-isoindole (7b). Brown oil. Rf (AcOEt/hexane 1:4) 0.29.
IR (neat): 1607, 1349, 1137. 1H-NMR (500 MHz): 1.14 (t, J ¼ 6.9, 3 H); 1.71 (s, 3 H); 2.95 – 3.01 (m, 1 H);
3.26 – 3.32 (m, 1 H); 3.90 (s, 3 H); 6.93 (dd, J ¼ 8.4, 2.3, 1 H); 7.11 (d, J ¼ 2.3, 1 H); 7.52 – 7.53 (m, 3 H);
7.61 (d, J ¼ 8.4, 1 H); 7.97 (dd, J ¼ 7.6, 1.5, 2 H). 13C-NMR (125 MHz): 15.5; 25.4; 55.7; 59.0; 102.2; 108.3;
114.4; 123.9; 128.3; 128.6; 129.9; 130.6; 134.0; 155.9; 161.3; 169.5. HR-MS: 282.1486 ([M þ H]þ,
C18H20NOþ2 ; calc. 282.1494). Anal. calc. for C18H19NO2 (281.35): C 76.84, H 6.81, N 4.98; found: C 76.75,
H 6.73, N 5.12.
3-(3-Chlorophenyl)-1-ethoxy-6-methoxy-1-methyl-1H-isoindole (7c). Brown oil. Rf (AcOEt/hexane
1:5) 0.34. IR (neat): 1607, 1343, 1138. 1H-NMR (500 MHz): 1.15 (t, J ¼ 7.6, 3 H); 1.70 (s, 3 H); 2.95 – 3.01
(m, 1 H); 3.24 – 3.30 (m, 1 H); 3.91 (s, 3 H); 6.94 (dd, J ¼ 8.4, 2.3, 1 H); 7.11 (d, J ¼ 2.3, 1 H); 7.46 (dd, J ¼
8.4, 7.6, 1 H); 7.51 (dd, J ¼ 8.4, 1.5, 1 H); 7.57 (d, J ¼ 8.4, 1 H); 7.84 (dt, J ¼ 7.6, 1.5, 1 H); 7.96 (t, J ¼ 1.5,
1 H). 13C-NMR (125 MHz): 15.5; 25.4; 55.7; 59.1; 102.4; 108.5; 114.5; 123.6; 126.4; 128.4; 129.4; 123.0;
130.6; 134.8; 135.7; 156.0; 161.5; 168.3. HR-MS: 316.1096 ([M þ H]þ, C18H19ClNO2þ ; calc. 316.1104).
Anal. calc. for C18H18ClNO2 (315.79): C 68.46, H 5.75, N 4.44; found: C 68.30, H 5.86, N 4.60.
We are grateful to Mrs. Miyuki Tanmatsu of our university for recording mass spectra and
performing combustion analyses.
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Received October 17, 2014