Synthesis of 2-Substituted 3-Alkylidene-2,3-dihydro-1H-isoindol-1-imines through cyclization of [1-(2-Cyanophenyl)alkylidene]aminide intermediates generated from the reaction of 2-(1-Azidoalkyl)benzonitriles with NaH

Article abstract of DOI:10.1002/hlca.201400261

A convenient sequence for the preparation of 3-alkylidene-2,3-dihydro-1H-isoindol-1-imine derivatives 6 has been developed. Thus, 2-(1-azidoalkyl)benzonitriles 2, readily accessible from 2- Alkylbenzonitriles, are allowed to react with NaH in DMF at 0 to

Full text of DOI:10.1002/hlca.201400261

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Helvetica Chimica Acta – Vol. 97 (2014)
Synthesis of 2-Substituted 3-Alkylidene-2,3-dihydro-1H-isoindol-1-imines
through Cyclization of [1-(2-Cyanophenyl)alkylidene]aminide Intermediates
Generated from the Reaction of 2-(1-Azidoalkyl)benzonitriles with NaH
by Kazuhiro Kobayashi*, Kosuke Ezaki, and Ippei Nozawa
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
convenient sequence for the preparation of 3-alkylidene-2,3-dihydro-1H-isoindol-1-imine
derivatives 6 has been developed. Thus, 2-(1-azidoalkyl)benzonitriles 2, readily accessible from 2-
alkylbenzonitriles, are allowed to react with NaH in DMF at 08 to room temperature to generate [1-(2-
cyanophenyl)alkylidene]aminide intermediates 3, of which cyclization and the subsequent rearrange-
ment, followed by alkylation with alkyl halides, affords 2-substituted 1-alkylidene-2,3-dihydro-1H-
isoindol-2-imines 6 in generally moderate yields.
Introduction. – Due to their biological significance [1], 2,3-dihydro-1H-isoindol-1-
imine derivatives have become of increasingly important, and several members of this
class of heterocycles have been recently synthesized [2]. On the other hand, in our
preceding study we have developed a novel method for the preparation of quinazolines
by cyclization of [1-(2-isocyanophenyl)alkylidene]amines, generated by the treatment
of 2-(1-azidoalkyl)phenyl isocyanides with NaH [3]. As an extension of this synthesis,
we became interested in investigating a similar generation of [1-(2-cyanophenyl)alkyl-
idene]aminides 3 from 2-(1-azidoalkyl)benzonitriles 2. We have found that the
reaction permits the construction of the 3-alkylidene-2,3-dihydro-1H-isoindol-1-imine
system. Herein, we report that 2-substituted 3-alkylidene-2,3-dihydro-1H-isoindol-1-
imines 6 can be conveniently synthesized by reacting 2, easily accessible from 2-
alkylbenzonitriles by a two-step sequence, with NaH, followed by treatment with alkyl
halides.
Results and Discussion. – The preparation of 6 was accomplished as outlined in
Scheme 1. 2-(1-Bromoalkyl)benzonitriles 1 were prepared by bromination of the
benzylic C-atom of 2-alkylbenzonitriles with N-bromosuccinimide (NBS) using
azobisisobutyronitrile (AIBN) as a catalyst in refluxing CCl4 [4] and were allowed to
react with NaN3 in DMF at room temperature to afford 2-(1-azidoalkyl)benzonitriles 2
in excellent yields. When the nitriles 2 were treated with NaH at 08, and the
temperature was raised to room temperature, evolution of probably H2 and N2, was
observed. After 30 min, alkyl halides were added, and the stirring was continued
overnight. The aqueous workup and the subsequent purification by column chroma-
tography on SiO2 afforded 6 in generally moderate yields, as compiled in the Table . The
conversion of 2-(1-azidopropyl)benzonitrile (1b) to 3-ethylidene derivatives 6h – 6j
ꢀ 2014 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 97 (2014)
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Scheme 1
Table. Preparation of 2-Substituted 3-Alkylidene-1H-isoindol-1-imines 6
Entry
2
R’X
6
Yielda) [%]
1
2
3
4
5
6
7
8
9
2a (R ¼ H)
BnBr
6a
6b
6c
6d
6e
6f
6g
6h
6i
64
66
53
43
60
62
26
37
43
38
2a
4-ClꢀC6H4CH2Cl
4-NO2ꢀC6H4CH2Br
BuBr
BnOCH2Cl
tBuOCOCH2Br
4-NO2ꢀC6H4F
BnBr
2a
2a
2a
2a
2a
2b (R ¼ Me)
2b
2b
BnOCH2Cl
tBuOCOCH2Br
10
6j
a) Yields of isolated products.
was shown to occur less efficiently under the conditions mentioned. The yields of these
products were lower than those of 3-methylidene derivatives (see Entries 8 – 10).
The structures of 6 were determined on the basis of NMR spectroscopy coupled
with IR, MS, and elemental analyses (see Exper. Part). For example, the structure of
6h, including the (Z)-configuration of the 3-ethylidene moiety, was confirmed by its
NOESY spectrum, in which strong interactions between the ethylidene Me group
(d(H) 1.86) and the benzyl CH2 group (d(H) 5.32), as well as between the vinyl H-atom
(d(H) 5.44) and the HꢀC(4) (d(H) 7.58), were observed.
The pathway leading to the formation of 6 may be explained as follows (Scheme 1).
The [1-(2-cyanophenyl)alkylidene]aminide intermediate 3 results from denitrogena-
tion from the benzylic anion intermediate. An intramolecular cyclization of 3 gives the
(3-alkyl-1H-isoindol-1-ylidene)aminide intermediate 4. Then, migration of one of the
a-H-atoms of alkyl group at C(3) to the imino N-atom gives rise to the 3-alkylidene-1-
imino-2,3-dihydro-1H-isoindol-2-ide intermediate 5. Trapping of this intermediate with
alkyl halides at the 2-position takes place selectively to result in the formation of 6.

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Trapping of a 2,3-dihydro-1-imino-3-methylidene-1H-isoindol-2-ide intermediate 5
(R ¼ H) with 1-fluoro-4-nitrobenzene could also be accomplished to afford 2,3-
dihydro-3-methylidene-2-(4-nitrophenyl)-1H-isoindol-1-imine (6g), albeit in consider-
ably lower yield (Entry 7). All attempts to obtain 2,3-dihydro-3-methylidene-1H-
isoindol-1-imine from 2a in a pure form, however, were unsuccessful, due to its
instability during chromatographic separation.
It should be noted that the reaction of 2-(azidomethyl)benzonitrile (7) [5] with
NaH, followed by BnBr under the same conditions for the formation of 6, resulted in
the formation of a considerably intractable mixture of products, presumably due to the
instability of (1H-isoindol-1-ylidene)iminide intermediate, 9, formed by cyclization of
(2-cyanophenyl)methylidenaminide (8; Scheme 2).
Scheme 2
In summary, we have shown that the reaction sequence starting with the treatment
of 2-(1-azidoalkyl)benzonitriles with NaH provides a convenient route to 3-alkylidene-
2,3-dihydro-1H-isoindol-1-imines. Since the starting materials are readily available, and
the operations are very simple, the present method may find some applications in
organic synthesis. Further study on heterocycle synthesis initiated by denitrogenation
from o-functionalized benzyl azides is under way in our laboratory.
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. M.p.:
Laboratory Devices MEL-TEMP II melting-point apparatus; uncorrected. IR Spectra: PerkinElmer
Spectrum 65 FT-IR spectrophotometer; ˜n in cmꢀ1. 1H- and 13C-NMR Spectra: JEOL ECP500 FT NMR
1
spectrometer (for H and 13C) or JEOL LA400 FT NMR spectrometer (at 500 or 400, and 125 MHz,
resp.), 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.
BuLi was supplied by Asia Lithium Corporation. All other chemicals used were commercially
available.
2-Ethylbenzonitrile [4]: Representative Procedure. A deep red soln. of 2-(lithiomethyl)benzonitriles,
generated by the treatment of 2-methylbenzonitrile (1.2 g, 10 mmol) with LDA (LiNiPr2; 20 mmol) in
diglyme (12.5 ml) as describe in [6], was treated with MeI (2.8 g, 20 mmol) under stirring. The deep red
color turned immediately to light red. Sat. aq. NH4Cl (50 ml) was added, and the mixture was warmed to
r.t. and extracted with AcOEt (3 ꢁ 30 ml). The combined extracts were washed with H2O (5 ꢁ 30 ml) and
brine (30 ml), dried (Na2SO4), and concentrated by evaporation. The residue was purified by CC to give
the title compound (0.89 g, 68%). Colorless liquid. Rf (AcOEt/hexane 1:10) 0.53. IR (neat) 2226, 1601.
1H-NMR (500 MHz): 1.30 (t, J ¼ 7.6, 3 H); 2.88 (q, J ¼ 7.6, 2 H); 7.28 (t, J ¼ 7.6, 1 H); 7.34 (d, J ¼ 7.6, 1 H);
7.52 (td, J ¼ 7.6, 1.5, 1 H); 7.61 (dd, J ¼ 7.6, 1.5, 1 H).

Helvetica Chimica Acta – Vol. 97 (2014)
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2-Propylbenzonitrile [7]. Yield: 87%. Pale-yellow liquid. Rf (AcOEt/hexane 1:10) 0.49. IR (neat):
2224. 1H-NMR (500 MHz): 0.99 (t, J ¼ 7.6, 3 H); 1.68 – 1.75 (m, 2 H); 2.82 (t, J ¼ 7.6, 2 H); 7.28 (t, J ¼ 7.6,
1 H); 7.31 (d, J ¼ 7.6, 1 H); 7.50 (t, J ¼ 7.6, 1 H); 7.61 (d, J ¼ 7.6, 1 H).
2-(1-Bromoalkyl)benzonitriles 1 were prepared by the bromination of respective 2-alkylbenzoni-
triles with NBS as described in [4] for the preparation of 1a.
2-(1-Bromoethyl)benzonitrile (1a). Yield: 92%. Pale-yellow liquid. Rf (AcOEt/hexane 1:10) 0.27. IR
(neat): 2227. 1H-NMR (400 MHz): 2.08 (d, J ¼ 6.8, 3 H); 5.54 (q, J ¼ 6.8, 1 H); 7.40 (ddd, J ¼ 7.8, 7.3, 1.0,
1 H); 7.62 – 7.66 (m, 2 H); 7.74 (dd, J ¼ 7.3, 1.5, 1 H). Anal. calc. for C9H8BrN (210.07): C 51.46, H 3.84, N
6.67; found: C 51.20, H 3.87, N 6.61.
2-(1-Bromopropyl)benzonitrile (1b). Yield: 94%. Colorless liquid. Rf (AcOEt/hexane 1:10) 0.29. IR
(neat): 2226. 1H-NMR (500 MHz): 1.05 (t, J ¼ 7.6, 3 H); 2.15 – 2.23 (m, 1 H); 2.29 – 2.38 (m, 1 H); 5.25 (t,
J ¼ 7.6, 1 H); 7.39 (td, J ¼ 7.6, 1.5, 1 H); 7.61 – 7.64 (m, 2 H); 7.69 (dd, J ¼ 8.4, 1.5, 1 H). Anal. calc. for
C10H10BrN (224.10): C 53.60, H 4.50, N 6.25; found: C 53.49, H 4.77, N 6.07.
2-(1-Azidoethyl)benzonitrile (2a): Representative Procedure. The mixture of 1a (1.3 g, 6.3 mmol) and
NaN3 (0.45 g, 6.9 mmol) in DMF (19 ml) was stirred at r.t. for 14 h. H2O (30 ml) was added, and the
mixture was extracted with AcOEt (3 ꢁ 20 ml). The combined extracts were washed with H2O (5 ꢁ
30 ml) and brine (30 ml), dried (Na2SO4), and concentrated by evaporation. The residue was purified
by CC to give 2a (0.98 g, 91%). Pale-yellow liquid. Rf (CH2Cl2/hexane 1:10) 0.47. IR (neat): 2226, 2102.
1H-NMR (500 MHz): 1.59 (d, J ¼ 6.9, 3 H); 5.09 (q, J ¼ 6.9, 1 H); 7.42 (td, J ¼ 7.6, 1.5, 1 H); 7.58 (d, J ¼ 7.6,
1 H); 7.63 – 7.69 (m, 2 H). Anal. calc. for C9H8N4 (172.19): C 62.78, H 4.68, N 32.54; found: C 62.71, H
4.72, N 32.50.
2-(1-Azidopropyl)benzonitrile (2b). Yield: 94%. Pale-yellow liquid. Rf (AcOEt/hexane 1:5) 0.62. IR
(neat): 2226, 2100. 1H-NMR (500 MHz): 0.99 (t, J ¼ 7.6, 3 H); 1.84 – 1.94 (m, 2 H); 4.87 (t, J ¼ 7.6, 1 H);
7.43 (t, J ¼ 7.6, 1 H); 7.54 (d, J ¼ 7.6, 1 H); 7.65 (t, J ¼ 7.6, 1 H); 7.68 (d, J ¼ 7.6, 1 H). Anal. calc. for
C10H10N4 (186.21): C 64.50, H 5.41, N 30.09; found: C 64.46, H 5.51, N 30.06.
2-Benzyl-2,3-dihydro-3-methylidene-1H-isoindol-1-imine (6a): Representative Procedure. To a stir-
red soln. of 2a (0.20 g, 1.2 mmol) in DMF (4 ml) at 08 was added NaH (60% mineral oil; 46 mg,
1.2 mmol) in several portions. The mixture was warmed to r.t., and stirring was continued for 30 min,
before BnBr (0.20 g, 1.2 mmol) was added dropwise. After stirring overnight at the same temp., sat. aq.
NH4Cl (20 ml) was added, and the mixture was extracted with AcOEt (3 ꢁ 10 ml). The combined
extracts were washed with H2O (2 ꢁ 15 ml) and brine (15 ml), dried (Na2SO4), and concentrated by
evaporation. The residue was purified by CC (AcOEt/hexane 1:2) to give 6a (0.15 g, 53%). Beige solid.
M.p. 130 – 1328 (hexane/CH2Cl2). IR (KBr) 3260, 1633, 1616. 1H-NMR (500 MHz): 4.51 (d, J ¼ 2.3, 1 H);
4.90 (d, J ¼ 2.3, 1 H); 5.07 (s, 2 H); 5.53 (br, 1 H); 7.21 – 7.32 (m, 5 H); 7.50 (t, J ¼ 7.6, 6.9, 1 H); 7.54 (t, J ¼
7.6, 1 H); 7.66 (d, J ¼ 7.6, 1 H); 7.71 (d, J ¼ 7.6, 1 H). 13C-NMR: 43.5; 84.5; 120.1; 121.2; 126.8; 127.1; 128.6;
129.0; 130.0; 130.8; 135.6; 137.2; 143.9; 162.2. HR-MS: 235.1212 ([M þ H]þ, C16H15N2þ ; calc. 235.1235).
Anal. calc. for C16H14N2 (234.30): C 82.02, H 6.02, N 11.96; found: C 81.97, H 6.05, N 11.94.
2-(4-Chlorobenzyl)-2,3-dihydro-3-methylidene-1H-isoindol-1-imine (6b). Beige solid. M.p. 90 – 928
(hexane/Et2O). IR (KBr): 3307, 1639, 1626. 1H-NMR (400 MHz): 4.47 (d, J ¼ 2.4, 1 H); 4.90 (d, J ¼ 2.4,
1 H); 5.04 (s, 2 H); 5.55 (br., 1 H); 7.20 (d, J ¼ 8.8, 2 H); 7.27 (d, J ¼ 8.8, 2 H); 7.50 (dd, J ¼ 7.8, 7.3, 1 H);
7.55 (td, J ¼ 7.3, 1.5, 1 H); 7.66 (d, J ¼ 7.8, 1 H); 7.74 (d, J ¼ 7.3, 1 H). 13C-NMR: 43.00; 84.5; 120.2; 121.2;
128.2; 128.7; 129.1; 129.6; 131.0; 132.8; 135.5; 135.8; 143.7; 162.2. HR-MS: 269.0832 ([M þ H]þ,
C16H14ClNþ2 ; calc. 269.0840). Anal. calc. for C16H13ClN2 (268.08): C 71.51, H 4.88, N 10.42; found: C 71.35,
H 4.90, N 10.35.
2,3-Dihydro-3-methylidene-2-(4-nitrobenzyl)-1H-isoindol-1-amine (6c). White needles. M.p. 110 –
1
1128 (hexane/CH2Cl2). IR (KBr): 3310, 1641, 1625, 1518, 1344. H-NMR (500 MHz): 4.43 (d, J ¼ 2.3,
1 H); 4.93 (d, J ¼ 2.3, 1 H); 5.17 (s, 2 H); 5.52 (br., 1 H); 7.42 (d, J ¼ 8.4, 2 H); 7.53 (t, J ¼ 7.6, 1 H); 7.58 (t,
J ¼ 7.6, 1 H); 7.69 (d, J ¼ 7.6, 1 H); 7.70 (d, J ¼ 7.6, 1 H); 8.16 (d, J ¼ 8.4, 2 H). 13C-NMR: 43.1; 84.5; 120.4;
121.2; 123.9; 127.6; 129.3; 131.2; 135.3; 137.6; 141.2; 143.6; 149.8; 158.8. HR-MS: 280.1073 ([M þ H]þ,
C16H14N3Oþ2 ; calc. 280.1086). Anal. calc. for C16H13N3O2 (279.10): C 68.81, H 4.69, N 15.05; found: C
68.75, H 4.90, N 14.80.
2-Butyl-2,3-dihydro-3-methylidene-1H-isoindol-1-imine (6d). Brown oil. Rf (AcOEt/hexane 1:3)
0.40. IR (neat): 3250, 1636, 1617. 1H-NMR (500 MHz): 0.97 (t, J ¼ 7.6, 3 H); 1.25 – 1.50 (m, 2 H); 1.66 –

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Helvetica Chimica Acta – Vol. 97 (2014)
1.74 (m, 2 H); 3.80 (t, J ¼ 7.6, 2 H); 4.57 (d, J ¼ 2.3, 1 H); 4.93 (d, J ¼ 2.3, 1 H); 5.47 (br., 1 H); 7.46 (td, J ¼
7.6, 1.5, 1 H); 7.51 (td, J ¼ 7.6, 1.5, 1 H); 7.65 (d, J ¼ 7.6, 1 H); 7.67 (d, J ¼ 7.6, 1 H). 13C-NMR: 13.9; 20.3;
29.7; 39.8; 83.2; 119.9; 120.3; 128.8; 129.0; 130.5; 135.5; 143.9; 164.1. HR-MS: 201.1383 ([M þ H]þ,
C13H17Nþ2 ; calc. 201.1392). Anal. calc. for C13H16N2 (200.28): C 77.96, H 8.05, N 13.99; found: C 77.93, H
8.25, N 13.87.
2,3-Dihydro-3-methylidene-2-[(phenylmethoxy)methyl]-1H-isoindol-1-imine (6e). Beige solid. M.p.
51 – 538 (hexane/Et2O). IR (KBr): 3301, 1645, 1628. 1H-NMR (500 MHz): 4.62 (s, 2 H); 4.87 (d, J ¼ 2.3,
1 H); 5.03 (d, J ¼ 2.3, 1 H); 5.43 (s, 2 H); 6.18 (br., 1 H); 7.26 (tt, J ¼ 7.6, 1.5, 1 H); 7.32 (td, J ¼ 7.6, 1.5,
2 H); 7.35 (dd, J ¼ 7.6, 1.5, 2 H); 7.49 (t, J ¼ 7.6, 1 H); 7.55 (td, J ¼ 7.6, 1.5, 1 H); 7.69 (d, J ¼ 7.6, 2 H).
13C-NMR: 69.7; 70.2; 85.5; 120.3; 121.3; 127.6; 127.8; 128.3; 128.4; 129.1; 131.2; 135.4; 137.8; 143.4; 162.5.
HR-MS: 265.1332 ([M þ H]þ, C17H17N2Oþ; calc. 265.1341). Anal. calc. for C17H16N2O (264.32): C 77.25,
H 6.10, N 10.60; found: C 77.33, H 6.25, N 10.03.
tert-Butyl (1,3-Dihydro-1-imino-3-methylidene-2H-isoindol-2-yl)acetate (6f). Beige solid. M.p.
1
85 – 878 (hexane/Et2O). IR (KBr): 3304, 1741, 1625. H-NMR (400 MHz): 1.47 (s, 9 H); 4.45 (d, J ¼
2.9, 1 H); 4.52 (s, 2 H); 4.95 (d, J ¼ 2.9, 1 H); 5.49 (br., 1 H); 7.47 (td, J ¼ 7.3, 1.0, 1 H); 7.53 (td, J ¼ 7.3,
1.0, 1 H); 7.64 (d, J ¼ 7.3, 1 H); 7.67 (d, J ¼ 7.3, 1 H). 13C-NMR: 28.0; 42.3; 82.1; 83.4; 120.3; 121.1; 129.0
(two overlapped Cs); 130.9; 135.4; 144.0; 162.1; 167.6. HR-MS: 259.1432 ([M þ H]þ, C15H19N2O2þ ;
calc. 259.1447). Anal. calc. for C15H18N2O2 (258.32): C 69.74, H 7.02, N 10.84; found: C 69.51, H 7.09,
N 10.87.
2,3-Dihydro-3-methylidene-2-(4-nitrophenyl)-1H-isoindol-1-imine (6g). Brown oil. Rf (AcOEt/
1
hexane 1:2) 0.50. IR (neat): 3296, 1630, 1520, 1347. H-NMR (400 MHz): 4.59 (d, J ¼ 2.3, 1 H); 5.07
(d, J ¼ 2.3, 1 H); 5.85 (br., 1 H); 7.58 (t, J ¼ 7.6, 1 H); 7.64 (d, J ¼ 8.4, 2 H); 7.76 (d, J ¼ 7.6, 1 H); 7.84 (d,
J ¼ 7.6, 1 H); 8.08 (t, J ¼ 7.6, 1 H); 8.41 (d, J ¼ 8.4, 2 H). 13C-NMR: 86.3; 115.6; 120.5; 122.0; 125.1; 126.1;
129.4; 129.9; 131.8; 141.5; 146.4; 155.0; 158.4. HR-MS: 266.0926 ([M þ H]þ, C15H12N3O2þ ; calc. 266.0930).
Anal. calc. for C15H11N3O2 (265.27): C 67.92, H 4.18, N 15.84; found: C 67.84, H 4.39, N 15.68.
(3Z)-2-Benzyl-3-ethylidene-2,3-dihydro-1H-isoindol-1-imine (6h). Beige solid. M.p. 69 – 708 (hex-
ane/Et2O). IR (KBr): 3304, 1634. 1H-NMR (500 MHz): 1.86 (d, J ¼ 7.6, 3 H); 5.32 (s, 2 H); 5.44 (q, J ¼
7.6, 1 H); 6.57 (br., 1 H); 7.18 (d, J ¼ 7.6, 2 H); 7.21 (t, J ¼ 7.6, 1 H); 7.30 (t, J ¼ 7.6, 2 H); 7.42 (dd, J ¼ 7.6,
6.9, 1 H); 7.50 (dd, J ¼ 7.6, 6.9, 1 H); 7.58 (d, J ¼ 7.6, 1 H); 7.67 (d, J ¼ 7.6, 1 H). 13C-NMR: 11.8; 45.5; 97.5;
119.1; 121.1; 125.7; 126.8; 127.8; 128.6; 130.6; 137.0; 137.3; 138.4; 142.6; 163.5. HR-MS: 249.1386 ([M þ
H]þ, C17H17Nþ2 ; calc. 249.1392). Anal. calc. for C17H16N2 (248.32): C 82.22, H 6.49, N 11.28; found: C
82.19, H 6.63, N 11.13.
(3Z)-3-Ethylidene-2,3-dihydro-2-[(phenylmethoxy)methyl]-1H-isoindol-1-imine (6i). Beige solid.
M.p. 61 – 638 (hexane/CH2Cl2). IR (KBr): 3260, 1621. 1H-NMR (500 MHz): 2.18 (d, J ¼ 7.6, 3 H); 4.68 (s,
2 H); 5.57 (s, 2 H); 5.59 (q, J ¼ 7.6, 1 H); 6.08 (br., 1 H); 7.24 (t, J ¼ 7.6, 1 H); 7.30 (t, J ¼ 7.6, 2 H); 7.35 (d,
J ¼ 7.6, 2 H); 7.40 (t, J ¼ 7.6, 1 H); 7.49 (t, J ¼ 7.6, 1 H); 7.57 (d, J ¼ 7.6, 1 H); 7.62 (d, J ¼ 7.6, 1 H).
13C-NMR: 11.8; 70.1; 70.9; 99.3; 119.2; 121.2; 127.4; 127.6; 127.9; 128.0; 128.2; 131.0; 136.5; 137.0; 138.2;
164.1. HR-MS: 279.1487 ([M þ H]þ, C18H19N2Oþ; calc. 279.1497). Anal. calc. for C18H18N2O (278.35): C
77.67, H 6.52, N 10.06; found: C 77.52, H 6.77, N 10.00.
tert-Butyl [(1Z)-1-Ethylidene-1,3-dihydro-3-imino-2H-isoindol-2-yl]acetate (6j). Colorless needles.
M.p. 81 – 838 (hexane/Et2O). IR (KBr): 3298, 1744, 1630. 1H-NMR (500 MHz): 1.48 (s, 9 H); 2.00 (d, J ¼
7.6, 3 H); 4.80 (s, 2 H); 5.47 (q, J ¼ 7.6, 1 H); 6.49 (br., 1 H); 7.38 (t, J ¼ 7.6, 1 H); 7.46 (t, J ¼ 7.6, 1 H); 7.55
(d, J ¼ 7.6, 1 H); 7.59 (d, J ¼ 7.6, 1 H). 13C-NMR: 11.5; 28.0; 44.7; 81.8; 96.8; 119.2; 120.9; 127.7; 128.0;
130.6; 136.9; 137.0; 163.5; 168.6. HR-MS: 273.1592 ([M þ H]þ, C16H21N2O2þ ; calc. 273.1598). Anal. calc.
for C16H20N2O2 (272.34): C 70.56, H 7.40, N 10.29; found: C 70.80, H 7.29, N 10.21.
This work was supported in part by JSPS KAKENHI Grant No. 26410051. Assistance in recording
mass spectra and performing combustion analyses by Mrs. Miyuki Tanmatsu of our university is gratefully
acknowledged.

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Received August 6, 2014