Formation of isoquinoline and 1-azetine derivatives via novel photocyclization of substituted α-dehydrophenylalanines

Article abstract of DOI:10.1016/S0040-4020(00)00188-5

The irradiation of substituted N-acetyl α-dehydrophenylalanines in MeOH with Pyrex-filtered light was found to give isoquinoline and 1-azetine derivatives in relatively good yields, which may be formed via intramolecular cyclization reactions from the (Z)

Full text of DOI:10.1016/S0040-4020(00)00188-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2941±2951
Formation of Isoquinoline and 1-Azetine Derivatives via Novel
Photocyclization of Substituted a-Dehydrophenylalanines
Hideki Hoshina,a Kanji Kubo,b Asako Moritaa and Tadamitsu Sakuraia,
*
aDepartment of Applied Chemistry, Faculty of Technology, Kanagawa University, Kanagawa-ku, Yokohama 221-8686, Japan
bInstitute of Advanced Material Study, 86, Kyushu University, Kasuga-Koen, Kasuga, Fukuoka 816-0811, Japan
Received 2 December 1999; accepted 2 March 2000
AbstractÐThe irradiation of substituted N-acetyl a-dehydrophenylalanines in MeOH with Pyrex-®ltered light was found to give isoquino-
line and 1-azetine derivatives in relatively good yields, which may be formed via intramolecular cyclization reactions from the (Z)- and (E)-
isomers, respectively. Solvent viscosity effects on the product distribution and composition strongly suggested the minor role of a radical pair
mechanism. In the presence of benzophenone as a triplet sensitizer, the starting (Z)-isomer underwent an exclusive isomerization into the
corresponding (E)-isomer without yielding any cyclization products, being consistent with the occurrence of the novel photocyclization
reactions from the excited singlet-state isomers. On the other hand, the irradiation of N-substituted benzoyl a-dehydrophenylalanines in
MeOH afforded selectively 1-azetine derivatives without forming any isoquinolines. It was suggested that the stereoelectronic effects of
bulky aromatic acyl groups are responsible for the complete suppression of the cyclization reactions, which eventually afford isoquinoline
derivatives via the excited singlet-state (Z)-isomers. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
ring-opening reactions of (Z)-2-methyl-N-butyl-4-(4-substi-
tuted benzylidene)-5(4H)- and (Z)-2-aryl-N-butyl-4-(4-
chlorobenzylidene)-5(4H)-oxazolones with butylamine.5
Synthetic organic photochemistry has continued to contri-
bute to the development of ef®cient and selective transfor-
mations for the preparation of natural products as well as
complicated molecules, which could not have been synthe-
sized by conventional methods.1 It is well-known that many
of the naturally occurring a,b-unsaturated-a-amino acids
(a-dehydroamino acids) and a-dehydropeptides possess a
variety of biological activities,2 allowing us to expect the
potential pharmacological and physiological usefulness of
these dehydroamino acid-derived products. Ef®cient
synthetic routes to a-dehydroamino acids and their deriva-
tives have been discovered,3 whereas there has been only
limited preliminary investigation of the photochemistry of
these dehydroamino acid derivatives.4 In this sense, the
photochemistry of substituted a-dehydroamino acids is an
unexplored ®eld of research. Accordingly, systematic study
is required to characterize the photochemical processes of
a-dehydroamino acids. Taking into account the fact that
aromatic ole®ns such as styrene and stilbene derivatives
show diverse excited-state reactivities of synthetic utility,
our attention is focused on the photoreactivity of aromatic
a-dehydroamino acids. This paper reports the novel photo-
cyclization reactions of (Z)-2-acylamino-N-butyl-3-(4-
substituted phenyl)-2-propenamides 1a±k obtained by the
Results and Discussion
Keywords: amino acid and derivatives; photochemistry; isoquinolines;
1-azetines.
* Corresponding author. Fax: 181-45-491-7915;
e-mail: tsakurai@kamome.cc.kanagawa-u.ac.jp
N-Acetyl a-dehydrophenylalanine derivatives 1a±e
The irradiation of a nitrogen-purged MeOH solution of 1d
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00188-5

2942
H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
Scheme 1.
(1.0£1022 mol dm23) with Pyrex-®ltered light (.280 nm)
from a 400 W high-pressure Hg lamp for 24 h at room
temperature gave product mixtures with Rf values of 0.26,
0.40, 0.70 and 0.86 on a silica gel TLC plate (EtOAc).
Column chromatography of the reaction mixtures over silica
gel allowed us to isolate (E)-isomer of 1d [(E)-1d; Rfˆ
0.26], the starting 1d [(Z)-1d; Rfˆ0.40], trans-2-methyl-3-
(4-chlorophenyl)-4-butylaminocarbonyl-1-azetine mono-
hydrate (2d; Rfˆ0.70) and 1-methyl-3-butylaminocar-
bonyl-7-chloroisoquinoline (3d; Rfˆ0.86) in 0.4, 6.8, 21
and 19% yields, respectively (Scheme 1). The structures
of the isolated products were determined based on their
spectroscopic and physical properties. The much lower
yield of (E)-1d than that expected from a 1H NMR analysis
of the mixtures may be due to, in part, conversion into the
thermodynamically more stable (Z)-1d during work-up.
into either the thermodynamically more stable trans-isomer
or the decomposition product(s).
The NMR analysis also revealed that there was formation of
the cis-azetine isomer, the isolation of which was unsuc-
cessful, having the vicinal coupling constants (J3,4)
(between protons on the azetine ring) of 9.4 (DMSO-d6)
and 10.9 Hz (CDCl3), along with the isolated trans-azetine
[J3,4ˆ7.2 (DMSO-d6) and 7.6 Hz (CDCl3)]. In order to
calculate the magnitude of J3,4 for these two isomers, we
®rst performed MM2 calculations of the model azetine:
2-methyl-3-phenyl-1-azetine and then obtained the dihedral
angles of 134.88 for the trans-isomer and 0.88 for the cis.
The combined use of these dihedral angles and the Karplus
equation6 made it possible to estimate the J3,4 values as 4.4
and 8.2 Hz for the trans- and cis-isomers, respectively. It is,
thus, reasonable to assign the azetine with larger J3,4 value to
the cis-isomer and that having the smaller value to the trans.
The structure of 2d was veri®ed also by 1H±1H and 13C±1H
COSY spectra. When the trans-azetine isomer was allowed
to stand for a few weeks at room temperature, there was
indication of the appearance of azetine-derived decompo-
sition product(s) (1H NMR analysis). It is likely that the
cis-isomer, which should be less stable, is mainly converted
1
The ®nding that H NMR spectrum obtained after 24 h
irradiation can be explained in terms of overlapping of the
spectra of 1d (Z and E), 2d (trans and cis) and 3d enabled us
to monitor the reaction by means of 1H NMR spectroscopy.
As seen from Table 1, after 0.5 h irradiation (E)-1d was
detected in 16% yield without leading to either 2d or 3d.
Additionally, its yield went up to 25% and then gradually
decreased as the reaction proceeded, indicating that the
isomerization of (Z)-1d to (E)-1d must take place prior to
the formation of 2d and 3d. In addition to the principle of
least motion,7 Chem 3D modeling of 1d suggests that the
(Z)- and (E)-isomers adopt most suitable conformations for
the intramolecular cyclization reactions that eventually give
substituted isoquinoline 3d and 1-azetine 2d, respectively.
Thus, we were led to propose Scheme 2 to explain the
observed product distribution.
Interestingly, the irradiation of 1d in MeOD or CD3OD
under similar conditions resulted in an incorporation of
Table 1. Relation between irradiation time and composition (%) of each compound in MeOH and MeCN
Compound
Solvent
Time (h)
0
0.5
1
3
6
12
18
24
(Z)-1d
(E)-1d
trans-2d
cis-2d
3d
MeOH
(MeCN)
MeOH
(MeCN)
MeOH
(MeCN)
MeOH
(MeCN)
MeOH
(MeCN)
100
(100)
84
(89)
16
78
(87)
19
(11)
1.1
71
(83)
20
(13)
3.9
(0.5)
1.2
(0.3)
3.5
56
(75)
25
(14)
10
(1.6)
2.7
(0.8)
6.8
44
(61)
22
(16)
16
(4.8)
5.0
(2.7)
12
31
(47)
18
(17)
27
(7.8)
7.0
(4.9)
18
20
(33)
14
(16)
34
(12)
8.0
(6.9)
24
(11)
(0.1)
0.3
1.3
(1.2)
(4.0)
(8.0)
(16)
(24)
(32)

H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
2943
Scheme 2.
deuterium at the 4-position on the azetine ring but did not
into the isoquinoline ring. Since the oxyl radical in the
assumed biradical intermediate I is considered to abstract
at ®rst the methyl hydrogen from MeOH and then to abstract
the hydroxy hydrogen of solvent-derived hydroxymethyl
radical affording eventually the 1-azetine 2d and formalde-
hyde, this ®nding provides a piece of evidence for the
proposed Scheme 2. Table 1 also shows that the change in
solvent from MeOH to MeCN results in a decrease of the
composition for (E)-1d and 2d with an increase of that for
(Z)-1d and 3d. Because the latter solvent has a lower reac-
tivity toward hydrogen abstraction than the former, this
demonstrates that suppression of both the isomerization
into (E)-1d and the hydrogen abstraction by the biradical
I, the precursor of 2d, causes an increase in the relative
composition of the isoquinoline 3d to the 1-azetine 2d,
being consistent with a mechanism shown in Scheme 2.
The great hydrogen-bonding solvation ability of MeOH
may be a factor determining this relative composition. On
the other hand, the irradiation of (Z)-1d in 2-propanol
(having a much smaller polarity than MeOH) under the
same conditions gave 3d in preference to 2d (composition
ratio, 3d/2d<1.5 at 12 h irradiation) but side reactions
occurred appreciably on prolonged irradiation. This ®nding
implies that the solvent polarity as well as the reactivity of a
given solvent toward hydrogen abstraction plays a major
role in determining the product composition and also in
controlling the undesirable side reactions.
fragmentation products, and that the quantum yields of
these rearrangement and fragmentation products are subject
to great solvent viscosity effects.9 Thus, we can expect the
appearance of both acetyl-rearranged and fragmented
products and then the observation of viscosity effects on
these product compositions, when (degassed and sealed)
CD3OD and CD3OD-glycerol-d8 (3:2 v/v) solutions of (Z)-
1d are irradiated with Pyrex-®ltered light. The obtained
results are presented in Table 2 and clearly show that
there are negligible products other than (E)-1d, trans- and
cis-2d and 3d. Additionally, the composition of each product
underwent solvent viscosity effects to only a negligible
extent, suggesting the minor role of a radical pair mechanism.
It is an important issue to elucidate the spin multiplicity of
the excited state from which the intramolecular cyclization
of 1 takes place forming eventually two different types of
heterocyclic rings. For this purpose we chose (Z)-1d as the
starting material and benzophenone (BP) as a triplet sensi-
tizer,9,10 and a nitrogen-purged MeCN solution of this
material containing BP was irradiated for a given period
of time with light of wavelengths longer than 340 nm,
which permitted selective excitation of the sensitizer. An
inspection of Table 3 reveals that the triplet BP accelerates
only the isomerization without forming any 1-azetine and
isoquinoline derivatives. Because a 1H NMR analysis of the
reaction mixtures showed no sign of the appearance of BP-
derived product(s), this ®nding strongly suggests that the
novel photocyclization reaction of 1 proceeds preferentially
through its excited singlet state.
The fact that the photo-Fries rearrangements8 as well as
acyloxy photomigrations9 proceed mainly through a caged
singlet radical pair intermediate forces us to discuss the
remaining possibility of the acetyl migration by a radical
pair mechanism. It was previously found that the direct
photolysis of N,O-diacyl-N-phenylhydroxylamines affords
1,3- and 1,5-acyloxy-migrated products along with
In order to obtain further information regarding factors that
control the selectivity of the observed photocyclization
reaction, we examined substituent effects on the product
Table 3. The composition of each compound obtained by the BP
(4.0£1022 mol dm23)-sensitized reaction of (Z)-1d (4.0£1023 mol dm23
)
Table 2. Viscosity effects on the composition of each compound obtained
by the irradiation of the starting (Z)-1d (1£1022 mol dm23) for 6 h at room
temperature
in nitrogen-saturated MeCN at room temperature
Irradiation
time (h)
Composition (%)
Solvent
Composition (%)
(Z)-1d
(E)-1d
trans-2d
cis-2d
3d
(Z)-1d (E)-1d trans-2d cis-2d 3d
0
1
3
6
100
55
50
49
0
0
0
0
0
0
0
0
0
0
0
0
0
45
50
51
CD3OD
CD3OD-glycerol-d8 (3:2 v/v)
34
33
22
23
16
14
2.0
3.1
26
27

2944
H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
Table 4. Substituent effects on the composition of each compound obtained by the irradiation of 1a±e (1.0£1022 mol dm23) in nitrogen-purged MeOH at room
temperature
Compound
Irradiation time (h)
Composition (%)
3/2
(Z)-1
(E)-1
trans-2
cis-2
3
1a (RˆOMe)
1b (RˆMe)
1c (RˆH)
0.5
24
0.5
24
0.5
24
0.5
24
74
26
82
22
81
20
84
20
91
55
24
12
18
12
16
10
16
14
9
0.9
11
0
16
0.8
22
0
34
0
7.0
0.3
8.0
0
8.0
0.3
7.0
0
8.0
0
1.0
0.8
43
0
42
1.6
41
0
24
0
22
2.3
1.8
1.4
0.6
2.8
1d (RˆCl)
1e (RˆCF3)
0.5
24
15
composition as well as on the composition ratio 3/2. As
shown in Table 4, the introduction of the strong electron-
withdrawing tri¯uoromethyl group lowers not only the
relative rate for the isomerization into (E)-form but also
the reactivity of the excited singlet-state 1. Interestingly,
both the methoxy (1a) and tri¯uoromethyl (1e) substituents
have a tendency to enhance the selectivity for the isoquino-
line derivative 3. The substituents attached at the 4-position
on the benzene ring of (Z)-1 are considered to exert their
electronic effects on the excited-state reactivity in a rather
complicated manner.
After a nitrogen-purged MeOH solution of 1f (4.0£
1023 mol dm23) was irradiated with Pyrex-®ltered light
(.280 nm) from a 400 W high-pressure Hg lamp for 20 h
at room temperature, the product mixture obtained was
subjected to column chromatography over silica gel,
which allowed us to isolate the starting 1f [(Z)-1f, 49%],
(E)-1f (9.1%) and trans-2-(4-tolyl)-3-(4-chlorophenyl)-4-
butylaminocarbonyl-1-azetine (trans-2f, 18%). The struc-
ture of trans-2f was con®rmed by comparison of its spectro-
scopic property with that of trans-2-methyl-3-(4-
1
chlorophenyl)-4-butylaminocarbonyl-1-azetine (2d). H±1H
and 13C±1H COSY spectra also substantiated our structure
determination. A careful H NMR analysis of the product
1
Although there are extensive synthetic routes to iso-
quinoline11 and 1-azetine12 derivatives, convenient photo-
chemical routes to these derivatives are scarcely known.13
The procedure for preparing the starting 1 is very simple and
is easily applicable to its related compounds. The photo-
reaction of substituted N-acetyl a-dehydrophenylalanines
described above should, therefore, ®nd application in the
simultaneous synthesis of various kinds of isoquinoline
and 1-azetine derivatives.
mixture revealed that there was a minor formation of the cis-
azetine isomer (cis-2f), though its isolation was unsuccess-
ful, with a negligible amount of the expected isoquinoline
derivative. When a DMSO-d6 solution of the trans-2f and
cis-2f was allowed to stand for several days at room
temperature, there was indication of the faster appearance
of the cis-2f-derived decomposition product(s) than that of
the trans-2f-derived one(s) (1H NMR analysis). It is, thus,
likely that the cis-isomer of lower stability is subjected to
either decomposition or isomerization (into the trans)
during the work-up.
N-Substituted benzoyl a-dehydrophenylalanine
derivatives 1f±k
On the basis of MM2 calculations and the Karplus equation6
described in the preceding section, we were able to assign
the azetine with larger vicinal coupling constant
(J3,4ˆ10.8 Hz) to the cis-isomer and that having the smaller
J3,4 value of 7.0 Hz to the trans, as shown below. In addition,
PM3 calculations of the model azetine: 2,3-diphenyl-4-
methylaminocarbonyl-1-azetine allowed us to estimate the
heat of formation for the trans-azetine and the cis as 231 and
In the preceding section we demonstrated that the photo-
reaction of N-acetyl a-dehydrophenylalanine derivatives
constitutes a new method for the preparation of substituted
isoquinolines and 1-azetines. As an extension of our study
on the photochemistry of a-dehydroamino acids, we
designed and synthesized (Z)-2-substituted benzoylamino-
N-butyl-3-(4-chlorophenyl)-2-propenamides (1f±k) in
order to investigate the effects of aromatic acyl groups on
the product distribution and composition derived from the
irradiation of 1a±e in MeOH.
Table 5. Relation between irradiation time and composition (%) of each
compound in MeOH
Compound
Time (h)
0
2
4
6
8
20
(Z)-1f
[(Z)-1j]
(E)-1f
100
[100]
85
[75]
13
81
[71]
14
79
[68]
14
75
[65]
14
58
[51]
13
[(E)-1j]
trans-2f
[trans-2j]
cis-2f
[22]
1.7
[2.4]
0.7
[23]
3.4
[4.2]
2.0
[25]
5.2
[5.9]
2.6
[25]
7.4
[7.9]
3.8
[27]
20
[16]
9.7
[cis-2j]
[0.7]
[1.3]
[1.6]
[2.3]
[6.2]

H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
2945
Scheme 3.
243 kJ mol21, respectively, showing that the trans-isomer is
thermodynamically more stable. Thus, our calculations are
consistent with the preferential formation of trans-2f.
that is a likely precursor of 2. In the preceding section it was
suggested that the isoquinoline is formed via the intra-
molecular cyclization reaction from the excited singlet-
state (Z)-isomer while the cyclization from the (E)-isomer
is responsible for the appearance of the 1-azetine. If we
adopt this mechanism for the simultaneous formation of
these two products, the much larger steric bulkiness of
aromatic acyl groups as compared with that of acetyl is
considered to suppress completely the attack of the acyl
carbonyl carbon upon the phenyl carbon resulting in an
exclusive deactivation of the excited-state (Z)-1 (Scheme
3).14 The stronger electron-withdrawing ability of aroyl
groups than acetyl may also play a role in causing such a
deactivation of the (Z)-isomer in the excited singlet state.
Signi®cantly, the results shown in Fig. 1 con®rm that there
is a good correlation between the relative rates at which (E)-
1 and 2 are generated. The increased rate for the isomeri-
zation has a propensity to accelerate the reaction that
eventually gives the azetine 2, being consistent with the
(E)-isomer, which serves as the precursor of 2. Because
(Z)-1f±k exhibit the ®rst absorption bands with almost
the same maximum wavelengths (lmaxˆ282±283 nm)
and molar extinction coef®cients (emaxˆ2.2±2.3£
104 dm3 mol21 cm21), it may be concluded that the isomeri-
zation of (Z)-1 to (E)-1 takes place in a higher ef®ciency on
introducing a stronger electron-donating substituent and a
more bulky one at the 4- and 2-positions on the benzene ring
of aromatic acyl group, respectively. No attempt could be
made to compare the isomerization ef®ciency between 1g
and 1f, h±k under the same reaction conditions, owing to
1H NMR spectra measured after 20 h irradiation clearly
showed that the reaction mixtures consisted of (Z)-1, (E)-
1, trans-2 and cis-2, and then contained negligible amounts
of isoquinoline derivatives, so that we attempted to monitor
the reactions by means of the H NMR spectroscopy. As
typically shown in Table 5, the fast isomerization of (Z)-1
should occur (prior to the production of 2) giving the (E)-1
1
Fig. 1. Correlation between the compositions of (E)-1 and 2 (trans1cis) obtained after 2 h [(E)-1] and 8 h (2) irradiations.

2946
H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
1
the poor solubility of 1g, the 20 h irradiation of which
(4.0£1024 mol dm23) afforded trans-2g (14%), cis-2g
(8.7%) and (E)-1g (15%) along with (Z)-1g (62%) without
forming any other products (1H NMR analysis).
1260 cm21. H NMR (500 MHz, CDCl3): d 2.40 (3H, s),
7.05 (1H, s), 7.39 (2H, d, Jˆ8.3 Hz), 8.01 (2H, d,
Jˆ8.3 Hz).
(Z)-2-Methyl-4-[4-(tri¯uoromethyl)benzylidene]-5(4H)-
oxazolone. Mp 110.0±112.08C. IR (KBr): 1806, 1779,
In conclusion, the photoreaction of the N-substituted
benzoyl a-dehydrophenylalanine derivatives in MeOH
provides a convenient route to the substituted 1-azetines.
1
1665, 1257 cm21. H NMR (500 MHz, CDCl3): d 2.43
(3H, s), 7.12 (1H, s), 7.68 (2H, d, Jˆ8.3 Hz), 8.18 (2H, d,
Jˆ8.3 Hz).
Experimental
(Z)-2-(4-Tolyl)-4-(4-chlorobenzylidene-5(4H)-oxazolone.
1
Mp 209.0±210.08C. IR (KBr): 1791, 1644, 1227 cm21. H
General
NMR (500 MHz, CDCl3): d 2.46 (3H, s), 7.15 (1H, s), 7.34
(2H, d, Jˆ7.9 Hz), 7.44 (2H, d, Jˆ8.6 Hz), 8.06 (2H, d,
Jˆ7.9 Hz), 8.14 (2H, d, Jˆ8.6 Hz).
1H and 13C NMR and IR spectra were taken with a JEOL
JNM-500 spectrometer and a Hitachi 270-30 infrared
spectrometer, respectively. Chemical shifts were deter-
mined using tetramethylsilane as an internal standard. UV
absorption spectra were recorded on a Shimadzu UV-2200
spectrophotometer. A cell with a 10-mm pathlength was
used. MeOH and MeCN were puri®ed according to the
standard procedures15 and freshly distilled prior to use.
2-Propanol was of spectroscopic grade and was used
without further puri®cation. All other reagents used were
obtained from commercial sources and were of the highest
grade available. MM2 and PM3 calculations were accom-
plished by using the Mac SPARTAN Plus available from
Wavefunction, Inc.
(Z)-2-Phenyl-4-(4-chlorobenzylidene-5(4H)-oxazolone.
Mp 192.5±193.58C. IR (KBr): 1797, 1770, 1656,
1
1236 cm21. H NMR (500 MHz, CDCl3): d 7.19 (1H, s),
7.43±7.63 (5H, m), 8.13±8.21 (4H, m).
(Z)-2-(4-Chlorophenyl)-4-(4-chlorobenzylidene)-5(4H)-
oxazolone. Mp 254.0±255.08C. IR (KBr): 1788, 1775,
1
1650, 1224 cm21. H NMR (500 MHz, CDCl3): d 7.21
(1H, s), 7.46 (2H, d, Jˆ8.5 Hz), 7.53 (2H, d, Jˆ8.5 Hz),
8.12 (2H, d, Jˆ8.5 Hz), 8.14 (2H, d, Jˆ8.5 Hz).
(Z)-2-(3-Chlorophenyl)-4-(4-chlorobenzylidene)-5(4H)-
oxazolone. Mp 181.0±1828C. IR (KBr): 1791, 1767, 1653,
1
1233 cm21. H NMR (500 MHz, CDCl3): d 7.21 (1H, s),
7.45±7.50 (3H, m) 7.58±7.60 (1H, m), 8.03 (1H, d,
General procedure for the synthesis of (Z)-2-methyl-4-
(4-substituted benzylidene)-5(4H)- and (Z)-2-substituted
phenyl-4-(4-chlorobenzylidene)-5(4H)-oxazolones
Jˆ7.9 Hz), 8.13 (2H, d, Jˆ8.6 Hz) 8.15 (1H, m).
(Z)-2-(2-Chlorophenyl)-4-(4-chlorobenzylidene)-5(4H)-
oxazolone. Mp 194.0±195.08C. IR (KBr): 1788, 1647,
N-Acylglycine (0.13 mol), 4-substituted benzaldehyde
(0.15 mol) and sodium acetate (0.10 mol) were added to
acetic anhydride (150 mL) and the resulting mixture was
heated at 70±858C for 1±2 h with stirring. The mixture
was cooled with ice and then poured into ice-water
(200 mL). The solid separated out was collected by ®ltration
with suction and washed with small amounts of cold EtOH.
After the crude product had been air-dried at room tempera-
ture, it was recrystallized from CCl4 to give yellow crystals
(40±60%).
1
1230 cm21. H NMR (500 MHz, CDCl3): d 7.26 (1H, s),
7.44 (1H, ddd, Jˆ1.2, 7.3, 7.9 Hz), 7.46 (2H, d,
Jˆ8.5 Hz), 7.52 (1H, ddd, Jˆ1.8, 7.3, 7.9 Hz), 7.59 (1H,
dd, Jˆ1.2, 7.9 Hz), 8.10 (1H, dd, Jˆ1.8, 7.9 Hz), 8.18 (2H,
d, Jˆ8.5 Hz).
(Z)-2-[4-(Tri¯uoromethyl)phenyl]-4-(4-chlorobenzylidene)-
5(4H)-oxazolone. Mp 254.0±255.08C. IR (KBr): 1788,
1
1761, 1653, 1230 cm21. H NMR (500 MHz, CDCl3): d
7.26 (1H, s), 7.47 (2H, d, Jˆ8.5 Hz), 7.80 (2H, d,
(Z)-2-Methyl-4-(4-methoxybenzylidene)-5(4H)-oxazolone.
Mp 109.5±110.08C. IR (KBr): 1800, 1776, 1662,
Jˆ8.5 Hz), 8.15 (2H, d, Jˆ8.5 Hz), 8.29 (2H, d, Jˆ8.5 Hz).
1
1263 cm21. H NMR (500 MHz, CDCl3): d 2.39 (3H, s),
3.87 (3H, s), 6.96 (2H, d, Jˆ8.5 Hz), 7.11 (1H, s), 8.06
General procedure for the synthesis of (Z)-2-acylamino-
N-butyl-3-(4-substituted phenyl)-2-propenamides
[(Z)-1a±k]
(2H, d, Jˆ8.5 Hz).
(Z)-2-Methyl-4-(4-methylbenzylidene)-5(4H)-oxazolone.
Mp 135.0±136.08C. IR (KBr): 1809, 1776, 1656,
1
1266 cm21. H NMR (500 MHz, CDCl3): d 2.38 (3H, s),
(Z)-2-Methyl-4-(4-substituted benzylidene)-5(4H)-oxazolone
or (Z)-2-(substituted phenyl)-4-(4-chlorobenzylidene)-
5(4H)-oxazolone (0.020 mol) was added to dry CH2Cl2
(200 mL) containing butylamine (0.021 mol) and the result-
ing solution was re¯uxed for 2±4 h. The reaction mixture
was washed successively with, 1 mol dm23 HCl (50 mL),
H2O (100 mL), 5 wt% NaHCO3 (50 mL) and H2O (100
mL), and then dried over anhydrous Na2SO4. After removal
of the solvent under reduced pressure, the solid residue
obtained was recrystallized from EtOH±hexane or EtOAc
affording colorless crystals (60±70%).
2.39 (3H, s), 7.11 (1H, s), 7.23 (2H, d, Jˆ8.3 Hz), 7.96
(2H, d, Jˆ8.3 Hz).
(Z)-2-Methyl-4-benzylidene-5(4H)-oxazolone. Mp 152.0±
152.58C. IR (KBr): 1779, 1659, 1266 cm21 1H NMR
.
(500 MHz, CDCl3): d 2.38 (3H, s), 7.13 (1H, s), 7.39±
7.44 (3H, m), 8.04±8.09 (2H, m).
(Z)-2-Methyl-4-(4-chlorobenzylidene-5(4H)-oxazolone.
Mp 143.0±144.08C. IR (KBr): 1800, 1773, 1659,

H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
2947
(Z)-2-Acetylamino-N-butyl-3-(4-methoxyphenyl)-2-pro-
penamide [(Z)-1a]. Mp 144.5±146.08C. IR (KBr): 3328,
7.13 (1H, s), 7.31 (2H, d, Jˆ8.2 Hz), 7.39 (2H, d, Jˆ
8.5 Hz), 7.55 (2H, d, Jˆ8.5 Hz), 7.89 (2H, d, Jˆ8.2 Hz),
8.15 (1H, t, Jˆ5.8 Hz), 9.85 (1H, s). 13C NMR (125.7 MHz,
DMSO-d6): d 13.7, 19.6, 21.0, 31.2, 38.9, 126.8, 127.9,
128.4, 128.8, 130.8, 130.9, 131.3, 132.7, 133.5, 141.6,
164.8, 165.6. Anal. Calcd (Found) for C21H23ClN2O2: C,
68.01 (68.19); H, 6.25 (6.45); N, 7.55% (7.52%).
1
3208, 1653, 1608 cm21. H NMR (500 MHz, DMSO-d6):
d 0.88 (3H, t, Jˆ6.8 Hz), 1.23±1.43 (4H, m), 200 (3H, s),
3.13 (2H, m), 3.77 (3H, s), 6.95 (2H, d, Jˆ8.3 Hz), 7.02
(1H, s), 7.50 (2H, d, Jˆ8.3 Hz), 7.89 (1H, br s), 9.29 (1H, s).
13C NMR (125.7 MHz, DMSO-d6): d 13.7, 19.5, 22.9, 31.3,
38.7, 55.1, 113.9, 126.7, 127.6, 128.1, 130.9, 159.3, 164.9,
169.2. Anal. Calcd (Found) for C16H22N2O3: C, 66.19
(66.51); H, 7.64 (7.42); N, 9.65% (9.63%).
(Z)-2-Benzoylamino-N-butyl-3-(4-chlorophenyl)-2-pro-
penamide [(Z)-1g]. Mp 217.0±2198C. IR (KBr): 3256,
1
1644, 1566 cm21. H NMR (500 MHz, DMSO-d6): d 0.88
(Z)-2-Acetylamino-N-butyl-3-(4-tolyl)-2-propenamide
[(Z)-1b]. Mp 148.0±149.08C. IR (KBr): 3322, 3208, 1653,
1617 cm21. 1H NMR (500 MHz, DMSO-d6): d 0.88 (3H, t,
Jˆ7.0 Hz), 1.27±1.43 (4H, m), 1.99 (3H, s), 2.30 (3H, s),
3.13 (2H, m), 6.99 (1H, s), 7.18 (2H, d, Jˆ8.3 Hz), 7.42
(2H, d, Jˆ8.3 Hz), 7.93 (1H, br, s), 9.31 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.7, 19.5, 20.8, 22.8, 31.2,
38.7, 127.4, 129.0, 129.2, 129.5, 131.4, 137.9, 164.8,
169.2. Anal. Calcd (Found) for C16H22N2O2: C, 70.04
(70.36); H, 8.08 (7.77); N, 10.21% (10.11%).
(3H, t, Jˆ6.8 Hz), 1.24±1.45 (4H, m), 3.15 (2H, dt, Jˆ6.2,
6.8 Hz), 7.14 (1H, s), 7.38±7.99 (9H, m), 8.16 (1H, t,
Jˆ6.2 Hz), 9.89 (1H, s). 13C NMR (125.7 MHz, DMSO-
d6): d 13.7, 19.5, 31.1, 38.8, 126.9, 127.8, 128.2, 128.4,
130.7, 131.1, 131.6, 132.7, 133.3, 133.4, 164.6, 165.7.
Anal Calcd (Found) for C20H21ClN2O2: C, 67.32 (67.17);
H, 5.93 (5.87); N, 7.85% (7.57%).
(Z)-2-(4-Cholorobenzoylamino)-N-butyl-3-(4-chloro-
phenyl)-2-propenamide [(Z)-1h]. Mp 187.0±189.08C. IR
(KBr): 3238, 1632, 1560 cm21 1H NMR (500 MHz,
.
(Z)-2-Acetylamino-N-butyl-3-phenyl-2-propenamide
[(Z)-1c]. Mp 147.0±1488C. IR (KBr): 3448, 1644,
DMSO-d6): d 0.88 (3H, t, Jˆ7.3 Hz), 1.30 (2H, tq, Jˆ7.3,
7.5 Hz), 1.46 (2H, tt, Jˆ7.3, 7.5 Hz), 3.15 (2H, dt, Jˆ5.6,
7.3 Hz), 7.17 (1H, s), 7.40 (2H, d, Jˆ8.5 Hz), 7.55 (2H, d,
Jˆ8.5 Hz), 7.59 (2H, d, Jˆ8.5 Hz), 8.00 (2H, d, Jˆ8.5 Hz),
8.18 (1H, t, Jˆ5.6 Hz), 9.98 (1H, s). 13C NMR (125.7 MHz,
DMSO-d6): d 13.7, 19.5, 31.2, 38.9, 127.2, 128.3, 128.5,
129.8, 130.1, 131.9, 132.4, 132.0, 133.3, 136.5, 164.6,
164.8. Anal. Calcd (Found) for C20H20Cl2N2O2: C, 61.39
(61.38); H, 5.15 (5.24); N, 7.16% (7.16%).
1
1614 cm21. H NMR (500 MHz, DMSO-d6): d 0.88 (3H,
t, Jˆ7.1 Hz), 1.20±1.48 (4H, m), 1.99 (3H, s), 3.14 (2H,
dt, Jˆ6.4, 6.4 Hz), 7.00 (1H, s), 7.35±7.53 (5H, m), 7.99
(1H, t, Jˆ6.4 Hz), 9.38 (1H, s), 9.38 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.7, 19.5, 22.8, 31.2, 38.8,
127.2, 128.3, 128.4, 129.2, 130.4, 134.2, 164.8, 169.3.
Anal. Calcd (Found) for C15H20N2O2: C, 69.21 (69.54); H,
7.74 (7.45); N, 10.76% (10.88%).
(Z)-2-(3-Chlorobenzoylamino)-N-butyl-3-(4-chlorophenyl)-
2-propenamide [(Z)-1i]. Mp 174.0±175.08C. IR (KBr):
(Z)-2-Acetylamino-N-butyl-3-(4-chlorphenyl)-2-propena-
mide [(Z)-1d]. Mp 153±154.58C. IR (KBr): 3448, 1650,
1
3268, 1632, 1554 cm21. H NMR (500 MHz, DMSO-d6):
1
1616 cm21. H NMR (500 MHz, DMSO-d6): d 0.88 (3H,
d 0.88 (3H, t, Jˆ7.6 Hz), 1.30 (2H, tq, Jˆ7.3, 7.6 Hz),
1.45 (2H, tt, Jˆ6.7, 7.3 Hz), 3.11 (2H, dt, Jˆ5.8, 6.7 Hz),
7.16 (1H, s), 7.41 (2H, d, Jˆ8.9 Hz), 7.54 (2H, d, Jˆ
8.9 Hz), 7.56 (1H, dd, Jˆ6.7, 7.6 Hz), 7.66 (1H, d, Jˆ
6.7 Hz), 7.93 (1H, d, Jˆ7.6 Hz), 8.05 (1H, s), 8.19 (1H, t,
Jˆ5.8, Hz), 10.00 (1H, s). 13C NMR (125.7 MHz, DMSO-
d6): d 13.7, 19.6, 31.2, 38.9, 126.6, 127.4, 127.8, 128.5,
130.3, 130.8, 131.5, 132.9, 133.1, 133.3, 135.6, 164.42,
164.45. Anal. Calcd (Found) for C20H20Cl2N2O2: C, 61.39
(60.98); H, 5.15 (5.25); N, 7.16% (6.87%).
t, Jˆ7.3 Hz), 1.29 (2H, tq, Jˆ7.3, 7.3 Hz), 1.43 (2H, tt,
Jˆ6.5, 7.3 Hz), 1.98 (3H, s), 3.13 (2H, dt, Jˆ6.5, 6.5 Hz),
6.95 (1H, s), 7.43 (2H, d, Jˆ8.5 Hz), 7.53 (2H, d,
Jˆ8.5 Hz), 7.99 (1H, t, Jˆ6.5 Hz), 9.36 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.7, 19.5, 22.8, 31.2, 38.8,
125.6, 128.4, 130.8, 131.0, 132.6, 133.2, 164.6, 169.2.
Anal. Calcd (Found) for C15H19ClN2O2: C, 61.12 (60.90);
H, 6.50 (6.40); N, 9.50% (9.40%).
(Z)-2-Acetylamino-N-butyl-3-[4-(tri¯uoromethyl)phenyl]-
2-propenamide [(Z)-1e]. Mp 158.0±159.08C. IR (KBr):
(Z)-2-(2-Chlorobenzoylamino)-N-butyl-3-(4-chlorophenyl)-
2-propenamide [(Z)-1j]. Mp 186.0±188.08C. IR (KBr):
1
3304, 1660, 1626 cm21. H NMR (500 MHz, DMSO-d6):
1
d 0.92 (3H, t, Jˆ7.3 Hz), 1.30 (2H, tq, Jˆ7.3, 7.3 Hz),
1.45 (2H, tt, Jˆ7.3, 7.3 Hz), 1.99 (3H, s), 3.15 (2H, dt,
Jˆ5.8, 7.3 Hz), 6.98 (1H, s), 7.70 (2H, d, Jˆ8.5 Hz), 7.73
(2H, d, Jˆ8.5 Hz), 8.10 (1H, t, Jˆ5.8 Hz), 9.48 (1H, s). 13C
NMR (125.7 MHz, DMSO-d6): d 13.7, 19.5, 22.9, 31.2,
38.8, 124.1 (q, Jˆ272 Hz), 124.6, 125.2 (q, Jˆ4 Hz),
127.8 (q, Jˆ32 Hz), 129.7, 132.7, 138.7, 164.5, 169.2.
Anal. Calcd (Found) for C16H19F3N2O2: C, 58.53 (58.65);
H, 5.83 (5.74); N, 8.53% (8.35%).
3340, 1614, 1512 cm21. H NMR (500 MHz, DMSO-d6):
d 0.89 (3H, t, Jˆ7.2 Hz), 1.33 (2H, tq, Jˆ7.2, 7.5 Hz),
1.48 (2H, tt, Jˆ7.2, 7.5 Hz), 3.21 (2H, dt, Jˆ5.7, 7.2 Hz),
7.09 (1H, s), 7.45±7.63 (8H, m), 7.94 (1H, t, Jˆ5.7 Hz),
10.00 (1H, s). 13C NMR (125.7 MHz, DMSO-d6): d 13.7,
19.5, 31.2, 38.9, 126.8, 127.3, 128.4, 129.2, 129.7, 130.0,
130.4, 131.0, 131.2, 132.9, 133.1, 135.8, 164.5, 165.7. Anal.
Calcd (Found) for C20H20Cl2N2O2: C, 61.39 (61.68); H, 5.15
(5.31); N, 7.16% (6.92%).
(Z)-2-(4-Toluoylamino)-N-butyl-3-(4-chlorphenyl)-2-pro-
penamide [(Z)-1f]. Mp 176.0±177.08C. IR (KBr): 3238,
(Z)-2-[4-(Tri¯uoromethyl) benzoylamino]-N-butyl-3-(4-
chlorophenyl)-2-propenamide [(Z)-1k]. Mp 175.0±
1
1632, 1527 cm21. H NMR (500 MHz, DMSO-d6): d 0.88
1768C. IR (KBr): 3244, 1635, 1527 cm21 1H NMR
.
(3H, t, Jˆ7.3 Hz), 1.30 (2H, tq, Jˆ7.3, 7.3 Hz), 1.44 (2H, tt,
(500 MHz, DMSO-d6): d 0.88 (3H, t, Jˆ7.3 Hz), 1.31
Jˆ7.3, 7.3 Hz), 2.38 (3H, s), 3.15 (2H, dt, Jˆ5.8, 7.3 Hz),
(2H, tq, Jˆ7.3, 7.5 Hz), 1.45 (2H, tt, Jˆ7.2, 7.5 Hz), 3.17

2948
H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
(2H, dt, Jˆ5.5, 7.2 Hz), 7.21 (1H, s), 7.41 (2H, d, Jˆ
8.6 Hz), 7.57 (2H, d, Jˆ8.6 Hz), 7.91 (2H, d, Jˆ7.9 Hz),
8.20 (2H, d, Jˆ7.9 Hz), 8.21 (1H, t, Jˆ5.5 Hz), 10.12 (1H,
s). 13C NMR (125.7 MHz, DMSO-d6): d 13.7, 19.5, 31.2,
38.9, 123.9 (q, Jˆ272 Hz), 125.3 (q, Jˆ3 Hz), 127.6, 128.5,
128.8, 130.7, 130.8, 131.5 (q, Jˆ31 Hz), 132.9, 133.2, 137.4,
164.4, 164.6. Anal. Calcd (Found) for C21H20ClF3N2O2: C,
59.36 (59.50); H, 4.75 (5.11); N, 6.60% (6.26%).
(E)-1d. Mp 143.0±144.08C. IR (KBr): 3334, 3262, 1644,
1
1630 cm21. H NMR (500 MHz, DMSO-d6): d 0.80 (3H,
t, Jˆ7.3 Hz), 1.10 (2H, tq, Jˆ7.3, 7.3 Hz), 1.29 (2H, tt,
Jˆ7.3, 7.3 Hz), 1.95 (3H, s), 3.01 (2H, dt, Jˆ7.3, 6.0 Hz),
6.82 (1H, s), 7.22 (2H, d, Jˆ8.4 Hz), 7.31 (2H, d,
Jˆ8.4 Hz), 8.10 (1H, t, Jˆ6.0 Hz), 9.62 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.5, 19.5, 23.3, 30.2, 38.4,
113.0, 127.9, 129.5, 130.8, 134.4, 134.5, 164.3, 165.2.
Anal. Calcd (Found for C15H19ClN2O2: C, 61.12 (60.79);
H, 6.50 (6.49); N, 9.50% (9.19%).
General procedure for the irradiation of (Z)-1a±k
A solution of (Z)-1 (0.40±1.0£1022 mol dm23) in MeOH
(500 mL), placed in a Pyrex vessel, was irradiated for a
given period of time under nitrogen with Pyrex-®ltered
light from a 400 W high-pressure Hg lamp at room tempera-
ture. At regular time intervals, an appropriate amount of the
solution (5 mL) being irradiated was pipetted off and
concentrated to dryness in vacuo giving the residue which
was subjected to 1H NMR analysis in DMSO-d6. The
composition was estimated from the area ratio of a given
1H NMR signal for each compound. After 24 h (1a±e) or
20 h (1f±k) irradiation the remaining solution was concen-
trated to dryness under reduced pressure and the resulting
residue was subjected to column chromatography over silica
gel (230 mesh, Merck) eluting with EtOAc±hexane. For the
purpose of isolating and purifying the photoproducts,
preparative TLC plate (silica gel) was also used. Physical
and spectroscopic properties of the isolated isomers (E)-1a±
k, substituted 1-azetines 2a±k and isoquinolines 3a±e are as
follows.
(E)-1e. Mp 154.0±155.08C. IR (KBr): 3340, 3274, 1650,
1
1640 cm21. H NMR (500 MHz, DMSO-d6): d 0.78 (3H,
t, Jˆ7.3 Hz), 1.06 (2H, tq, Jˆ7.3, 7.3 Hz), 1.27 (2H, tt,
Jˆ7.0, 7.3 Hz) 1.97 (3H, s), 3.01 (2H, dt, Jˆ5.8, 7.0 Hz),
6.93 (1H, s), 7.40 (2H, d, Jˆ8.2 Hz), 7.60 (2H, d,
Jˆ8.2 Hz), 8.17 (1H, t, Jˆ5.8 Hz), 9.78 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.5, 19.5, 23.4, 30.2, 38.5,
112.4, 124.4 (q, Jˆ271 Hz), 124.8 (q, Jˆ4 Hz), 126.6 (q,
Jˆ32 Hz), 128.0, 136.1, 140.0, 164.2, 168.5. Anal. Calcd
(Found) for C16H19F3N2O2: C, 58.53 (58.22); H, 5.83 (5.56);
N, 8.53% (8.33%).
(E)-1f. Mp 140.0±141.08C. IR (KBr): 3298, 1641,
1
1539 cm21. H NMR (500 MHz, DMSO-d6): d 0.81 (3H,
t, Jˆ7.3 Hz), 1.18 (2H, tq, Jˆ7.3, 7.3 Hz), 1.42 (2H, tt,
Jˆ7.2, 7.3 Hz), 2.38 (3H, s), 3.04 (2H, dt, Jˆ5.8, 7.2 Hz),
6.69 (1H, s), 7.29 (2H, d, Jˆ8.2 Hz), 7.32 (2H, d, Jˆ
8.5 Hz), 7.34 (2H, d, Jˆ8.5 Hz), 7.83 (2H, d, Jˆ8.2 Hz),
8.08 (1H, t, Jˆ5.8 Hz), 10.02 (1H, s). 13C NMR (125.7 MHz,
DMSO-d6): d 13.6, 19.6, 21.0, 30.3, 38.6, 116.0, 127.8,
128.0, 128.9, 129.8, 131.0, 131.2, 134.2, 134.7, 141.8,
164.3, 164.7. Anal. Calcd (Found) for C21H23ClN2O2: C,
68.01 (67.78); H, 6.25 (6.63); N, 7.55% (7.20%).
(E)-1a. Mp 126.0±127.08C. IR (KBr): 3328, 3274, 1650,
1
1611 cm21. H NMR (500 MHz, DMSO-d6): d 0.81 (3H,
t, Jˆ7.3 Hz), 1.24 (2H, tq, Jˆ7.3, 7.3 Hz), 1.31 (2H, tt,
Jˆ7.3, 7.3 Hz), 1.93 (3H, s), 3.02 (2H, dt, Jˆ6.1, 7.3 Hz),
3.73 (3H, s), 6.71 (1H, s), 6.83 (2H, d, Jˆ8.6 Hz), 7.16 (2H,
d, Jˆ8.6 Hz), 7.97 (1H, t, Jˆ6.1 Hz), 9.47 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.6, 19.5, 23.3, 30.3, 38.4,
54.9, 113.4, 115.0, 127.6, 129.1, 132.1, 158.0, 164.7,
167.9. Anal. Calcd (Found) for C16H22N2O3: C, 66.19
(65.97); H, 7.64 (7.50); N, 9.65% (9.50%).
(E)-1g. Mp 144.0±145.08C. IR (KBr): 3274, 1626,
1
1521 cm21. H NMR (500 MHz, DMSO-d6): d 0.82 (3H,
t, Jˆ7.3 Hz), 1.14 (2H, tq, Jˆ7.3, 7.3 Hz), 1.33 (2H, tt,
Jˆ7.3, 7.3 Hz), 3.05 (2H, dt, Jˆ5.5, 7.3 Hz), 6.71 (1H, s),
7.30 (2H, d, Jˆ8.5 Hz), 7.35 (2H, dd, Jˆ7.3, 7.3 Hz), 7.58
(1H, dd, Jˆ7.3, 7.3 Hz), 7.91 (2H, d, Jˆ7.3 Hz), 8.11 (1H, t,
Jˆ5.5 Hz), 10.12 (1H, s). 13C NMR (125.7 MHz, DMSO-
d6): d 13.6, 19.5, 30.2, 38.5, 116.1, 127.6, 127.9, 128.2,
129.7, 131.2, 131.6, 133.7, 134.0, 164.0, 164.7. Anal.
Calcd (Found) for C20H21ClN2O2: C, 67.32 (67.30); H,
5.93 (6.63); N, 7.85% (7.95%).
(E)-1b. Mp 149.0±150.08C. IR (KBr): 3334, 3274, 1650,
1
1640 cm21. H NMR (500 MHz, DMSO-d6): d 0.88 (3H,
t, Jˆ7.3 Hz), 1.13 (2H, tq, Jˆ7.3, 7.3 Hz), 1.31 (2H, tt,
Jˆ7.3, 7.3 Hz), 1.94 (3H, s), 2.26 (3H, s), 3.01 (2H, dt,
Jˆ6.1, 7.3 Hz), 6.76 (1H, s), 7.06 (2H, d, Jˆ8.2 Hz), 7.12
(2H, d, Jˆ8.2 Hz), 7.98 (1H, t, Jˆ6.1 Hz), 9.50 (1H, s). 13C
NMR (125.7 MHz, DMSO-d6): d 13.6, 19.5, 20.6, 23.3,
30.2, 38.5, 114.8, 127.8, 128.5, 132.4, 133.1, 135.7, 164.6,
168.0. Anal. Calcd (Found) for C16H22N2O2: C, 70.04
(69.73); H, 8.08 (8.04); N, 10.21% (10.05%).
(E)-1h. Mp 185.0±186.08C. IR (KBr): 3292, 1644,
1
1539 cm21. H NMR (500 MHz, DMSO-d6): d 0.82 (3H,
t, Jˆ7.3 Hz), 1.15 (2H, tq, Jˆ7.3, 7.3 Hz), 1.33 (2H, tt,
Jˆ7.0, 7.3 Hz), 3.05 (2H, dt, Jˆ5.8, 7.0 Hz), 6.71 (1H, s),
7.30 (2H, d, Jˆ8.6 Hz), 7.35 (2H, d, Jˆ8.6 Hz), 7.59 (2H, d,
Jˆ8.6 Hz), 7.94 (2H, d, Jˆ8.6 Hz), 8.11 (1H, t, Jˆ5.8 Hz),
10.18 (1H, s). 13C NMR (125.7 MHz, DMSO-d6): d 13.6,
19.5, 30.2, 38.5, 116.5, 128.0, 128.4, 129.6, 129.8, 131.3,
132.5, 133.9, 134.3, 136.5, 163.8, 164.0. Anal. Calcd
(Found) for C20H21Cl2N2O2: C, 61.39 (61.53); H, 5.15
(5.03); N, 7.16% (7.13%).
(E)-1c. Mp 131.0±132.08C. IR (KBr): 3298, 1660,
1
1632 cm21. H NMR (500 MHz, DMSO-d6): d 0.80 (3H,
t, Jˆ7.3 Hz), 1.13 (2H, tq, Jˆ7.3, 7.3 Hz), 1.30 (2H, tt,
Jˆ7.3, 7.3 Hz), 1.95 (3H, s), 3.00 (2H, dt, Jˆ6.1, 7.3 Hz),
6.81 (1H, s), 7.17 (1H, dd, Jˆ6.7, 6.7 Hz), 7.22±7.27 (4H,
m), 8.31 (1H, t, Jˆ6.1 Hz), 9.56 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.6, 19.5, 23.3, 30.2, 38.4,
114.5, 126.4, 127.8, 127.9, 133.8, 135.3, 164.5, 168.1.
Anal. Calcd (Found for C15H20N2O2: C, 69.21 (69.18); H,
7.74 (7.80); N, 10.76% (10.93%).
(E)-1i. Mp 119.0±121.08C. IR (KBr): 3304, 1626, 1527
1
cm21. H NMR (500 MHz, DMSO-d6): d 0.82 (3H, t, Jˆ
7.3 Hz), 1.15 (2H, tq, Jˆ7.3, 7.3 Hz), 1.33 (2H, tt, Jˆ7.0,
7.3 Hz), 3.06 (2H, dt, Jˆ5.8, 7.0 Hz), 6.72 (1H, s), 7.31 (2H,

H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
2949
d, Jˆ8.5 Hz), 7.36 (2H, d, Jˆ8.5 Hz), 7.55 (1H, dd, Jˆ7.9,
7.9 Hz), 7.66 (1H, d, Jˆ7.9 Hz), 7.87 (1H, d, Jˆ7.9 Hz),
7.97 (1H, s), 8.15 (1H, t, Jˆ5.8 Hz), 10.24 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.6, 19.6, 30.3, 38.5, 116.8,
126.5, 127.5, 128.0, 129.8, 130.4, 131.4, 131.5, 133.1,
133.9, 134.2, 135.8, 163.4, 163.9 Anal. Calcd (Found) for
C20H20Cl2N2O2: C, 61.39 (61.28); H, 5.15 (5.49); N, 7.16%
(7.18%).
1.27 (2H, tq, Jˆ7.3, 7.3 Hz), 1.41 (2H, tt, Jˆ7.0, 7.3 Hz),
2.06 (3H, s), 3.10 (2H, dt, Jˆ5.8, 7.0 Hz), 4.32 (1H, d, Jˆ
7.3 Hz), 5.50 (1H, d, Jˆ7.3 Hz), 7.30 (2H, d, Jˆ7.6 Hz),
7.34 (1H, dd, Jˆ7.3, 7.3 Hz), 7.40 (2H, dd, Jˆ7.3, 7.6 Hz),
7.91 (1H, br s). 13C NMR (125.7 MHz, DMSO-d6) d 13.5,
13.6, 19.5, 31.1, 38.3, 76.9, 82.6, 125.5, 128.2, 128.7, 140.4,
164.9, 169.8. This azetine was slowly decomposed so that
we could not obtain the satisfactory result of elemental
analysis.
(E)-1j. Mp 139.0±141.08C. IR (KBr): 3236, 1638,
1
1524 cm21. H NMR (500 MHz, DMSO-d6): d 0.82 (3H,
trans-2-Methyl-3-(4-chlorophenyl)-4-butylaminocarbonyl-
1-azetine (trans-2d). Mp 42.0±43.08C. IR (KBr): 3310,
t, Jˆ7.3 Hz), 1.14 (2H, tq, Jˆ7.3, 7.3 Hz), 1.33 (2H, tt,
Jˆ7.3, 7.3 Hz), 3.04 (2H, dt, Jˆ6.1, 7.3 Hz), 6.80 (1H, s),
7.30 (2H, d, Jˆ8.6 Hz), 7.35 (2H, d, Jˆ8.6 Hz), 7.38±7.54
(4H, m), 8.19 (1H, t, Jˆ6.1 Hz), 10.26 (1H, s). 13C NMR
(125.7 MHz, DMSO-d6): d 13.6, 19.6, 30.2, 38.5, 115.1,
127.0, 128.0, 129.1, 129.6, 129.7, 130.1, 131.2, 131.3,
134.0, 134.3, 136.0, 163.8, 164.6. Anal. Calcd (Found) for
C20H20Cl2N2O2: C, 61.39 (61.05); H, 5.15 (5.38); N, 7.16%
(7.04%).
1
1677, 1617 cm21. H NMR (500 MHz, DMSO-d6): d 0.87
(3H, t, Jˆ7.4 Hz), 1.26 (2H, tq, Jˆ7.4, 7.4 Hz), 1.40 (2H, tt,
Jˆ7.0, 7.4 Hz), 2.06 (3H, d, Jˆ1.4 Hz), 3.10 (2H, dt, Jˆ6.0,
7.0 Hz), 4.30 (1H, dd, Jˆ1.4, 7.2 Hz), 5.51 (1H, d, Jˆ
7.2 Hz), 7.34 (2H, d, Jˆ8.3 Hz), 7.47 (2H, d, Jˆ8.3 Hz),
7.90 (1H, t, Jˆ6.0 Hz). 13C NMR (125.7 MHz, DMSO-d6):
d 13.5, 13.6, 19.5, 31.1, 38.3, 76.8, 81.9, 127.4, 128.7,
132.7, 139.4, 164.9, 169.7. EI-MS: m/z (%) 296 (M1,
0.36), 298 (M112, 0.10). Anal. Calcd (Found) for
C15H19ClN2O´H2O: C, 60.70 (60.70); H, 7.13 (7.13); N,
9.44% (9.43%).
(E)-1k. Mp 234.0±236.08C. IR (KBr): 3256, 1644,
1
1539 cm21. H NMR (500 MHz, DMSO-d6): d 0.82 (3H,
t, Jˆ7.3 Hz), 1.15 (2H, tq, Jˆ7.3, 7.3 Hz), 1.33 (2H, tt,
Jˆ7.0, 7.3 Hz), 3.06 (2H, dt, Jˆ5.5, 7.0 Hz), 6.75 (1H, s),
7.31 (2H, d, Jˆ8.6 Hz), 7.36 (2H, d, Jˆ8.6 Hz), 7.90 (2H, d,
Jˆ8.2 Hz), 8.11 (2H, d, Jˆ8.2 Hz), 8.17 (1H, t, Jˆ5.5 Hz),
10.35 (1H, s). 13C NMR (125.7 MHz, DMSO-d6): d 13.6,
19.5, 30.3, 38.5, 116.9, 123.9 (q, Jˆ275 Hz), 125.3 (q,
Jˆ3 Hz) 128.0, 128.6, 129.8, 131.2 (q, Jˆ32 Hz), 131.4,
133.9, 134.1, 137.6, 163.7, 163.9. Anal. Calcd (Found) for
C21H20ClF3N2O2: C, 59.36 (59.22); H, 4.75 (4.60); N, 6.60%
(6.50%).
trans-2-Methyl-3-[4-(tri¯uoromethyl)phenyl]-4-butyl-
aminocarbonyl-1-azetine (trans-2e). Oily liquid. IR (neat):
3322, 1653, 1595 cm21. 1H NMR (500 MHz, DMSO-d6): d
0.87 (3H, t, Jˆ7.3 Hz), 1.27 (2H, tq, Jˆ7.3, 7.3 Hz), 1.42
(2H, tt, Jˆ7.0, 7.3 Hz), 2.09 (3H, d, Jˆ1.2 Hz), 3.08±3.18
(2H, m), 4.34 (1H, dd, Jˆ1.2, 7.3 Hz), 5.62 (1H, d, Jˆ
7.3 Hz), 7.55 (2H, d, Jˆ8.2 Hz), 7.78 (2H, d, Jˆ8.2 Hz),
7.92 (1H, t, Jˆ5.5 Hz). 13C NMR (125.7 MHz, DMSO-d6):
d 13.5, 13.6, 19.5, 31.1, 38.3, 76.8, 81.8, 124.0 (q,
Jˆ272 Hz), 125.6 (q, Jˆ4 Hz), 126.2, 128.6 (q, Jˆ32 Hz),
145.1, 164.9, 169.6. Anal. Calcd (Found) for
C16H19F3N2O´H2O: C, 58.17 (58.49); H, 6.41 (6.06); N,
8.48% (8.46%).
trans-2-Methyl-3-(4-methoxyphenyl)-4-butylaminocar-
bonyl-1-azetine (trans-2a). Oily liquid. IR (neat): 3316,
1
1640, 1611 cm21. H NMR (500 MHz, DMSO-d6): d 0.82
(3H, t, Jˆ7.3 Hz), 1.26 (2H, tq, Jˆ7.3, 7.3 Hz), 1.40 (2H, tt,
Jˆ7.0, 7.3 Hz), 2.03 (3H, d, Jˆ1.2 Hz), 3.13 (2H, dt, Jˆ6.0,
7.0 Hz), 3.76 (3H, s), 4.31 (1H, dd, Jˆ1.2, 7.3 Hz), 5.44
(1H, d, Jˆ7.3 Hz), 6.95 (2H, d, Jˆ8.6 Hz), 7.23 (2H, d,
Jˆ 8.6 Hz), 7.89 (1H, br s). 13C NMR (125.7 MHz,
DMSO-d6): d 13.6 (2C), 19.4, 31.1, 38.2, 55.1, 76.6, 82.7,
114.1, 127.2, 131.2, 132.2, 164.8, 164.9. Anal. Calcd
(Found) for C16H22N2O2´H2O: C, 65.73 (65.91); H, 8.27
(7.94); N, 9.58% (9.22%).
trans-2-(4-Tolyl)-3-(4-chlorophenyl)-4-butylaminocar-
bonyl-1-azetine (trans-2f). Oily liquid. IR (neat): 3400,
1
1650, 1615 cm21. H NMR (500 MHz, DMSO-d6): d 0.88
(3H, t, Jˆ7.3 Hz), 1.28 (2H, tq, Jˆ7.3, 7.6 Hz), 1.43 (2H, tt,
Jˆ7.2, 7.6 Hz), 2.39 (3H, s), 3.14 (2H, dt, Jˆ5.5, 7.2 Hz),
4.58 (1H, d, Jˆ7.0 Hz), 5.75 (1H, d, Jˆ7.0 Hz), 7.34 (2H, d,
Jˆ8.2 Hz), 7.39 (2H, d, Jˆ8.5 Hz), 7.49 (2H, d, Jˆ8.5 Hz),
7.88 (2H, d, Jˆ8.2 Hz), 8.06 (1H, t, Jˆ5.5 Hz), 13C NMR
(125.7 MHz, DMSO-d6): d 13.6, 19.5, 21.1, 31.1, 38.4,
76.8, 82.1, 123.9, 127.4, 128.2, 128.8, 129.2, 132.8, 139.3,
142.1, 163.3, 169.5. Anal. Calcd (Found) for
C21H23ClN2O´H2O: C, 67.64 (67.89); H, 6.76 (6.36); N,
7.51% (7.15%).
trans-2-Methyl-3-(4-tolyl)-4-butylaminocarbonyl-1-azetine
(trans-2b). Oily liquid. IR (neat): 3322, 1653, 1590 cm21
.
1H NMR (500 MHz, DMSO-d6): d 0.87 (3H, t, Jˆ7.3 Hz),
1.26 (2H, tq, Jˆ7.3, 7.3 Hz), 1.40 (2H, tt, Jˆ7.0, 7.3 Hz),
2.04 (3H, d, Jˆ1.2 Hz), 2.30 (3H, s), 3.09 (2H, dt, Jˆ5.8,
7.0 Hz), 4.29 (1H, dd, Jˆ1.2, 7.3 Hz), 5.45 (1H, d, Jˆ
7.3 Hz), 7.18 (2H, d, Jˆ8.3 Hz), 7.21 (2H, d, Jˆ8.3 Hz),
7.98 (1H, t, Jˆ5.8 Hz). 13C NMR (125.7 MHz, DMSO-d6):
d 13.5, 13.6, 19.5, 20.7, 31.1, 38.3, 76.8, 82.7, 125.5, 129.2,
137.4, 137.5,164.9, 169.9. Anal. Calcd (Found) for
C16H22N2O´H2O: C, 69.53 (69.14); H, 8.75 (8.69); N,
10.14% (10.30%).
trans-2-Phenyl-3-(4-chorophenyl)-4-butylaminocarbonyl-
1-azetine (trans-2g). Oily liquid. IR (neat): 3310, 1644,
1
1610 cm21. H NMR (500 MHz, DMSO-d6): d 0.87 (3H,
t, Jˆ7.3 Hz), 1.28 (2H, tq, Jˆ7.3, 7.3 Hz), 1.43 (2H, tt,
Jˆ7.0, 7.3 Hz), 3.11 (2H, dt, Jˆ5.8, 7.0 Hz), 4.60 (1H, d,
Jˆ7.3 Hz), 5.76 (1H, d, Jˆ7.3 Hz), 7.39 (2H, d, Jˆ8.5 Hz),
7.48 (2H, d, Jˆ8.5 Hz), 7.52 (2H, dd, Jˆ7.6, 7.6 Hz), 7.61
(1H, dd, Jˆ7.6, 7.6 Hz), 7.98 (2H, d, Jˆ7.6 Hz), 8.05 (1H, t,
Jˆ5.8 Hz). 13C NMR (125.7 MHz, DMSO-d6): d 13.6, 19.5,
31.1, 38.4, 76.8, 82.3, 126.6, 127.5, 128.2, 128.7, 128.8,
132.1, 132.9, 139.2, 163.3, 169.5. Anal. Calcd (Found) for
trans-2-Methyl-3-phenyl-4-butylaminocarybonyl-1-azetine
.
(trans-2c). Oily liquid. IR (neat): 3310, 1656, 1590 cm21
1H NMR (500 MHz, DMSO-d6): d 0.87 (3H, t Jˆ7.3 Hz)

2950
H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
C20H21ClN2O´H2O: C, 66.94 (66.58); H, 6.46 (6.12); N,
7.81% (7.50%).
(oily liquid) whose 1H and 13C NMR spectra were consistent
with the proposed structure, although the cis-isomer isolated
was contaminated with the azetine-derived decomposition
product(s): 1H NMR (500 MHz, DMSO-d6): dˆ0.73 (3H, t,
Jˆ7.0 Hz), 0.90±0.97 (4H, m), 2.70±2.79 (2H, m), 5.12
(1H, d, Jˆ10.7 Hz), 6.07 (1H, d, Jˆ10.7 Hz), 7.25 (2H, d,
Jˆ8.2, Hz), 7.36 (2H, d, Jˆ8.5, Hz), 7.59 (1H, dd, Jˆ7.6,
8.2 Hz), 7.69±7.73 (2H, m), 7.94 (1H, d, Jˆ7.6 Hz), 8.01
(1H, br s). 13C NMR (125.7 MHz, DMSO-d6): d 13.6, 19.4,
30.9, 37.9, 73.7, 82.4, 126.8, 127.7, 127.8, 128.5, 129.9,
130.8, 131.9, 132.6, 133.4, 135.3, 163.3, 167.0.
trans-2-(4-Chlorophenyl)-3-(4-chlorophenyl)-4-butyl-
aminocarbonyl-1-azetine (trans-2h). Mp 107.0±109.08C.
1
IR (KBr): 3292, 1644, 1596 cm21. H NMR (500 MHz,
DMSO-d6): d 0.88 (3H, t, Jˆ7.3 Hz), 1.27 (2H, tq, Jˆ7.3,
7.6 Hz), 1.43 (2H, tt, Jˆ7.3, 7.6 Hz), 3.13 (2H, dt, Jˆ5.8,
7.3 Hz), 4.62 (1H, d, Jˆ7.3 Hz), 5.78 (1H, d, Jˆ7.3 Hz),
7.40 (2H, d, Jˆ8.5 Hz), 7.49 (2H, d, Jˆ8.5 Hz), 7.61 (2H, d,
Jˆ8.8 Hz), 8.00 (2H, d, Jˆ8.8 Hz), 8.08 (1H, t, Jˆ5.8 Hz),
13C NMR (125.7 MHz, DMSO-d6): d 13.6, 19.4, 31.0, 38.4,
76.8, 82.6, 125.5, 127.5, 128.8, 128.9, 130.0, 132.9, 136.9,
138.9, 162.4, 169.3. Anal. Calcd (Found) for
C20H20Cl2N2O´H2O: C, 61.08 (61.25); H, 5.64 (5.29); N,
7.12% (6.86%).
3-Butylaminocarbonyl-7-methoxy-1-methylisoquinoline
1
(3a). Mp 105.0±106.08C. IR (KBr): 3376, 1656 cm21. H
NMR (500 MHz, DMSO-d6): d 0.92 (3H, t, Jˆ7.3, Hz),
1.37 (2H, tq, Jˆ7.3, 7.3 Hz), 1.56 (2H, tt, Jˆ7.0, 7.3 Hz),
2.94 (3H, s), 3.37 (2H, dt, Jˆ6.1, 7.0 Hz), 3.98 (3H, s), 7.48
(1H, dd, Jˆ2.4, 8.8 Hz), 7.51 (1H, d, Jˆ2.4 Hz), 8.08 (1H,
d, Jˆ8.8 Hz), 8.31 (1H, s), 8.66 (1H, t, Jˆ6.1 Hz). 13C NMR
(125.7 MHz, DMSO-d6): d 13.7, 19.7, 22.3, 31.5, 38.4,
55.6, 104.4, 118.0, 123.1, 129.3, 130.3, 130.8, 140.8,
156.0, 159.2, 164.2. Anal. Calcd (Found) for C16H20N2O2:
C, 70.56 (70.23); H, 7.40 (7.07); N, 10.29% (10.64%).
trans-2-(3-Chlorophenyl)-3-(4-chlorophenyl)-4-butyl-
aminocarbonyl-1-azetine (trans-2i). Mp 73.0±74.08C. IR
(KBr): 3272, 1648, 1600 cm21 1H NMR (500 MHz,
.
DMSO-d6): d 0.88 (3H, t, Jˆ7.3 Hz), 1.28 (2H, tq, Jˆ7.3,
7.3 Hz), 1.44 (2H, tt, Jˆ6.7, 7.3 Hz), 3.11 (2H, dt, Jˆ5.8,
6.7 Hz), 4.64 (1H, d, Jˆ7.3 Hz), 5.79 (1H, d, Jˆ7.3 Hz),
7.42 (2H, d, Jˆ8.5 Hz), 7.49 (2H, d, Jˆ8.5 Hz), 7.58 (1H,
dd, Jˆ7.9, 8.1 Hz), 7.70 (1H, dd, Jˆ1.5, 8.1 Hz), 7.93 (1H,
dd, Jˆ1.5, 7.9 Hz), 8.01 (1H, dd, Jˆ1.5, 1.5 Hz), 8.10 (1H,
t, Jˆ5.8, Hz). 13C NMR (125.7 MHz, DMSO-d6): d 13.6,
19.5, 31.1, 38.4, 76.7, 82.7, 126.8, 127.6, 127.8, 128.6,
128.8, 130.8, 131.9, 133.0, 133.4, 138.9, 162.1, 169.3.
Anal. Calcd (Found) for C20H20Cl2N2O´0.5H2O: C, 62.51
(62.32); H, 5.51 (5.52); N, 7.26% (7.29%).
3-Butylaminocarbonyl-7-methyl-1-methylisoquinoline
1
(3b). Mp 67.0±69.08C. IR (KBr): 3436, 1658 cm21. H
NMR (500 MHz, DMSO-d6): d 0.92 (3H, t, Jˆ7.3 Hz),
1.35 (2H, tq, Jˆ7.3, 7.6 Hz), 1.54 (2H, tt, Jˆ7.3, 7.6 Hz),
2.57 (3H, s), 2.94 (3H, s), 3.35 (2H, dt, Jˆ6.1, 7.3 Hz), 7.68
(1H, dd, Jˆ1.2, 8.5 Hz), 8.04 (1H, dd, Jˆ8.5 Hz), 8.06 (1H,
d, Jˆ1.2 Hz), 8.32 (1H, s), 8.69 (1H, t, Jˆ6.1 Hz). 13C NMR
(125.7 MHz, DMSO-d6): d 13.7, 19.6, 21.6, 22.1, 31.5,
38.4, 118.0, 124.7, 128.0, 128.4, 132.8, 133.7, 138.7,
141.8, 156.8, 164.1. Anal. Calcd (Found) for C16H20N2O:
C, 74.97 (75.21); H, 7.86 (7.83); N, 10.93% (11.04%).
trans-2-(2-Chlorophenyl)-3-(4-chlorophenyl)-4-butyl-
aminocarbonyl-1-azetine (trans-2j). Oily liquid. IR (neat):
3396, 1642, 1592 cm21. 1H NMR (500 MHz, DMSO-d6): d
0.88 (3H, t, Jˆ7.3 Hz), 1.30 (2H, tq, Jˆ7.3, 7.6 Hz), 1.44
(2H, tt, Jˆ7.0, 7.6 Hz), 3.16 (2H dt, Jˆ5.5, 7.0 Hz), 4.59
(1H, d, Jˆ7.6 Hz), 5.79 (1H, d, Jˆ7.6, Hz), 7.45 (2H, d,
Jˆ8.6, Hz), 7.49 (1H, dd, Jˆ1.3, 7.3 Hz), 7.51 (2H, d,
Jˆ8.6, Hz), 7.57±7.64 (2H, m), 7.91 (1H, dd, Jˆ1.5,
7.8 Hz), 8.02 (1H, t, Jˆ5.5 Hz). 13C NMR (125.7 MHz,
DMSO-d6): d 13.6, 19.4, 31.0, 38.4, 76.7, 82.5, 126.3,
127.3, 127.6, 128.8, 130.6, 131.7, 132.2, 132.7, 133.0,
138.9, 162.1, 169.2. Anal. Calcd (Found) for
C20H20Cl2N2O´H2O: C, 61.08 (61.39); H, 5.64 (5.44); N,
7.12% (7.08%).
3-Butylaminocarbonyl-1-methylisoquinoline (3c). Mp
66.0±67.08C. IR (KBr) 3310, 1656 cm21
.
1H NMR
(500 MHz, DMSO-d6): d 0.92 (3H, t, Jˆ7.3 Hz), 1.35
(2H, tq, Jˆ7.3, 7.3 Hz), 1.57 (2H, t, Jˆ7.0, 7.3 Hz), 2.98
(3H, s), 3.37 (2H, dt, Jˆ6.1, 7.0 Hz), 7.78 (1H, ddd, Jˆ1.2,
7.0, 8.2 Hz), 7.85 (1H, ddd, Jˆ1.2, 7.0, 8.2 Hz), 8.15 (1H, d,
Jˆ8.2 Hz), 8.29 (1H, d, Jˆ8.2 Hz), 8.38 (1H, s), 8.75 (1H, t,
Jˆ6.1 Hz). 13C NMR (125.7 MHz, DMSO-d6): d 13.7, 19.6,
22.1, 31.4, 38.4, 118.1, 125.9, 127.8, 128.6, 128.8, 130.8,
135.5, 142.5, 157.7, 163.9. Anal. Calcd (Found) for
C15H18N2O: C, 74.35 (74.16); H, 7.49 (7.34); N, 11.56%
(11.64%).
trans-2-[4-(Tri¯uoromethyl)phenyl]-3-(4-chlorophenyl)-
4-butylaminocarbonyl-1-azetine (trans-2k). Mp 63.0±
65.08C. IR (KBr): 3292, 1650, 1600 cm21
.
1H NMR
3-Butylaminocarbonyl-7-chloro-1-methylisoquinoline (3d).
1
(500 MHz, DMSO-d6): d 0.88 (3H, t, Jˆ7.3 Hz), 1.30
(2H, tq, Jˆ7.3, 7.3 Hz), 1.44 (2H, tt, Jˆ7.3, 7.3 Hz), 3.15
(2H, dt, Jˆ5.8, 7.3 Hz), 4.68 (1H, d, Jˆ7.3 Hz), 5.84 (1H, d,
Jˆ7.3 Hz), 7.43 (2H, d, Jˆ8.5 Hz), 7.50 (2H, d, Jˆ8.5 Hz),
7.91 (2H, d, Jˆ8.2 Hz), 8.14 (1H, t, Jˆ5.8 Hz), 8.20 (2H, d,
Jˆ8.2 Hz). 13C NMR (125.7 MHz, DMSO-d6): d 13.6, 19.5,
31.0, 38.4, 76.8, 82.8, 125.7 (q, Jˆ3 Hz), 126.2 (a,
Jˆ273 Hz), 127.6, 128.8, 129.1, 130.5, 131.8 (q,
Jˆ32 Hz), 133.0, 138.8, 162.2, 169.1. Anal. Calcd
(Found) for C20H20ClF3N2O´0.5H2O: C, 60.36 (60.44); H,
5.07 (5.24); N, 6.70% (6.35%).
Mp 91.0±92.08C. IR (KBr): 3400, 1668 cm21. H NMR
(500 MHz, DMSO-d6): d 0.92 (3H, t, Jˆ7.3 Hz), 1.34
(2H, tq, Jˆ7.3, 7.3 Hz), 1.56 (2H, tt, Jˆ6.7, 7.3 Hz), 2.96
(3H, s), 3.35 (2H, dt, Jˆ6.1, 6.7 Hz), 7.87 (1H, dd, Jˆ2.0,
8.7 Hz), 8.22 (1H, d, Jˆ8.7 Hz), 8.35 (1H, d, Jˆ2.0 Hz),
8.41 (1H, s), 8.76 (1H, t, Jˆ6.1 Hz). 13C NMR (125.7 MHz,
DMSO-d6): d 13.7, 19.6, 22.2, 31.4, 38.5, 117.8, 125.0,
128.5, 130.9, 131.4, 133.2, 134.1, 143.0, 157.3, 163.7.
Anal. Calcd (Found) for C15H17ClN2O: C, 65.10 (65.47);
H, 6.19 (6.16); N, 10.12% (10.03%).
3-Butylaminocarbonyl-7-tri¯uoromethyl-1-methyliso-
quinoline (3e). Mp 104.0±105.08C. IR (KBr): 3384,
cis-2i. We succeeded in isolating a slight amount of cis-2i

H. Hoshina et al. / Tetrahedron 56 (2000) 2941±2951
2951
1662 cm21. 1H NMR (500 MHz, DMSO-d6): d 0.93 (3H, t,
Jˆ7.3 Hz), 1.36 (2H, tq, Jˆ7.3, 7.6 Hz), 1.57 (2H, tt, Jˆ7.3,
7.6 Hz), 3.06 (3H, s), 3.37 (2H, dt, Jˆ6.1, 7.3 Hz), 8.10 (1H,
dd, Jˆ1.2, 8.5 Hz), 8.40 (1H, d, Jˆ8.5 Hz), 8.49 (1H, d,
Jˆ1.2, Hz), 8.62 (1H, s), 8.85 (1H, t, Jˆ6.1, Hz). 13C
NMR (125.7 MHz, DMSO-d6): d 13.7, 19.9, 22.2, 31.4,
38.6, 117.8, 123.87 (q, Jˆ4 Hz), 123.88 (q, Jˆ272 Hz),
126.0, 126.8, 128.4 (q, Jˆ32 Hz), 130.5, 137.4, 144.5,
159.3, 163.5. Anal. Calcd (Found) for C16H17F3N2O: C,
61.93 (61.85); H, 5.52 (5.50); N, 9.03% (9.43%).
1986, 59, 3917±3923; Sato, Y.; Nakajima, Y.; Shin, C. Hetero-
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Viscosity and sensitization effects on the photoreactivity
of (Z)-1d
For the purpose of examining sensitization effects on the
product distribution and composition, an MeCN solution
(40 mL) of (Z)-1d (4.0£1023 mol dm23) containing BP
(4.0£1022 mol dm23), placed in a Pyrex vessel, was
irradiated under nitrogen at room temperature with light
of wavelengths longer than 340 nm (Corning 0±52 glass
®lter) from a 450 W high-pressure Hg lamp. At suitable
time intervals, an aliquot (5 mL) of the solution was pipetted
off and concentrated to dryness in vacuo. The resulting resi-
9. Sakurai, T.; Yamamoto, H.; Yamada, S.; Inoue, H. Bull. Chem.
Soc. Jpn. 1985, 58, 1174±1181; Sakurai, T., Sukegawa, H., Inoue,
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Soc. Jpn. 1991, 64, 2140±2147; Sakurai, T.; Utsumi, K.; Ohkita,
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1956; Nagakubo, H.; Kubota. G.; Kubo, K.; Kaneko, T.; Sakurai,
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1
due was dissolved in DMSO-d6 and subjected to H NMR
analysis. On the other hand, we employed a H NMR tube
1
instead of a Pyrex vessel in order to investigate viscosity
effects on the photoreactivity. A CD3OD or a CD3OD-
glycerol-d8 (3:2 v/v) solution of (Z)-1d (1£1022 mol
dm23) was placed in an NMR tube and sealed after the
solution was degassed with nitrogen. This degassed and
sealed solution was irradiated for 6 h at room temperature
with Pyrex-®ltered light from a 450 W high-pressure Hg
lamp.
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