A synthesis of 2,3,4,5-tetrahydro-1H-3-benzazepines via Pummerer-type cyclization of N-(2-arylethyl)-N-(2-Phenylsulfinylethyl)formamides

Article abstract of DOI:10.3987/com-00-8982

A construction of 2,3,4,5-tetrahydro-1H-3-benzazepine ring system (7) was achieved via Pummerer-type cyclization of N-(2-arylethyl)-N-2-(phenylsulfinylethyl)formamides (6). This route produced the benzazepines (10) and (11) in six steps starting from readily available 2-arylethylamines (2) and 2-chloroethyl phenyl sulfide.

Full text of DOI:10.3987/com-00-8982

HETEROCYCLES, Vol. 53, No. 9, 2000, pp. 2009 - 2018, Received, 22nd June, 2000
A SYNTHESIS OF 2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINES VIA
PUMMERER-TYPE
CYCLIZATION
OF
N-(2-ARYLETHYL)-N-
(2-PHENYLSULFINYLETHYL)FORMAMIDES
Jun Toda, Tsuyoshi Ichikawa, Toshiaki Saitoh, Yoshie Horiguchi, and
Takehiro Sano*
Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida,
Tokyo 194-8543, Japan.
Abstract - A construction of 2,3,4,5-tetrahydro-1H-3-benzazepine ring system
(7) was achieved via Pummerer-type cyclization of N-(2-arylethyl)-N-2-
(phenylsulfinylethyl)formamides (6). This route produced the benzazepines (10)
and (11) in six steps starting from readily available 2-arylethylamines (2) and
2-chloroethyl phenyl sulfide.
2,3,4,5-Tetrahydro–1H-3-benzazepine derivatives have received considerable attention, in part due to their
interesting pharmacological activities observed in the compounds (1), a class of dopamine receptor antagonists
and neuroleptics.1 In a series of paper we reported the synthesis of 1,2,3,4-tetrahydroisoquinolines,2 and
1,2,3,4-tetrahydroquinolines3 using an aromatic cyclization of the in situ formed thionium ion generated under
the acidic conditions from a sulfinyl precursor (Pummerer reaction).4 We now describe a further extension of
this method to the synthesis of 2,3,4,5-tetrahydro-1H-3-benzazepines.5
Preparation of Sulfoxides
N-(2-Arylethyl)-N-(2-phenylsulfinylethyl)formamides (6a-b), substrates of

the Pummerer-type cyclization, were prepared from 2-arylethylamines (2a-b) via the route shown in Scheme 1.
A mixture of 2a-b and 2-chloroethyl phenyl sulfide in dioxane was heated under reflux for 3 days in the
presence of a phase transfer catalyst to afford secondary amines (3a-b) in good yields, although the undesired
dialkyl derivatives (4a-b) were accompanied as a minor product. The amines (3a-b) were then treated with
formic acid-acetic anhydride to give N-formyl derivatives (5a-b). Oxidation of 5a-b with sodium metaperiodate
in aqueous methanol gave sulfoxides (6a-b) in good overall yields.
Cl
R
PhS
R
R
R
R
NH
+
N(CH2CH2SPh)2
NH2
R
Na2CO3, NaI, TBAB
in dioxane, reflux
PhS
2
3
4
For compounds 2-11
a: R=OMe, b: R=H
HCOOH-Ac2O
70°C, 1 h
R
HO
R
R
R
NaIO4
in MeOH-H2O
N
Me
N
CHO
N
CHO
HO
R
SPh
PhS
PhS
O
1 R= H or Cl
5
6
Scheme 1
Pummerer Reaction. The sulfoxide (6a), on treatment with trifluoroacetic anhydride (TFAA) in benzene at
room temperature for 24 h (method A), readily induced the cyclization to afford 3-formyl-7,8-dimethoxy-1-
phenylsulfanyl-1H-3-benzazepine (7a) in 80% yield. On the other hand, the sulfoxide (6b) lacking an OMe
group in the benzene ring, when treated as described above, did not induce the cyclization and merely produced
a disulfide (8b) in 38 % yield. In our previous investigations,2 we found that a similar cyclization, in the
presence of BF3•Et2O used as an additive reagent proceeded in a highly effective manner, particularly in the
cases of the aromatic ring with weak nucleophilicity. In fact, application of this reaction (method B) for the
sulfoxide (6b) induced the cyclization to afford 3-formyl-1-phenylsulphanyl-2,3,4,5-tetrahydro-1H-
3-benzazepine (7b) in 47% yield, although 8b and a sulfide (5b) were accompanied as minor products. The
reaction of 6a under the method B condition only decreased the yield of 7a (63%), although the reaction was

much accelerated.
The results demonstrated that the Pummerer reaction is applicable for the construction of the 3-benzazepine
ring even in the substrate whose nucleophilic aromatic ring is not activated by electron donating group such as
OMe. However, this cyclization is less effective than that achieved in the 1,2,3,4-tetrahydroisoquinoline
synthesis via this reaction.2
R
Pummerer reaction
N
CHO
N
CHO
+
+
6
5b
R
A: TFAA in benzene, rt
PhS
SPh
PhS
B: TFAA-BF3·Et2O in benzene, rt
7
8b
NiCl2-NaBH4
20% NaOH
R
NH
R
R
R
N
CHO
10
11
R
R
Scheme 2
LiAlH4
9
N Me
Preparation of 2,3,4,5-Tetrahydro-1H-3-benzazepines. Reductive removal of the phenylsulfanyl group of
7a-b proceeded by treatment with NiCl2-NaBH4 in MeOH-THF to give N-formyl-3-benzazepines (9a-b) in
good yields. Deprotection of the N-formyl group was readily achieved by conventional methods. Alkaline
hydrolysis of 9a-b gave 3-benzazepines (10a-b). Reduction of 9a-b with LiAlH4 gave N-methylbenzazepines
(11a-b).
Thus, this route produces the benzazepines (10a) and (11a) in 38 and 24% overall yields, respectively, from
commercially available homoveratrylamine (2a) and 2-chloroethyl phenyl sulfide, thus providing a convenient
and general method of 3-benzazepine synthesis. The benzazepines (10a) and (11a) are the synthetic
intermediates of biologically important 3-benzazepines (1).1, 6
EXPERIMENTAL

General Notes. Melting points were taken on a Yanagimoto SP-M1 hot-stage melting point apparatus. TLC was
performed on Merck precoated Silica gel 60 F254 plates (Merck). Column chromatography was carried out with
silica gel (Wakogel C-200). Medium pressure liquid chromatography (MPLC) was performed on Kusano CIG
prepacked column. IR spectra were obtained as KBr disks with a HORIBA FT-710 spectrophotometer and are
given in cm-1. NMR spectra were measured on a JEOL JNM-EX90 (1H-NMR 90 MHz, 13C-NMR 22.5 MHz) or
JEOL JMS-AL 300 (1H-NMR 300 MHz, 13C-NMR 75.0 MHz) spectrometer in CDCl3 with tetramethylsilane as
an internal standard, and the chemical shifts are given in δ values. Low-resolution MS spectra (LR-MS) and
high-resolution MS spectra (HR-MS) were determined on a JEOL JMS-HX110A or JMS-D300 spectrometer at
30 eV with a direct inlet system. The organic extract from each reaction mixture was washed with brine, dried
over anhydrous Na2SO4 before concentration in vacuo.
Alkylation of 1 with 2-Chloroethyl Phenyl Sulfide. Typical Procedure. A mixture of 2a (1.0 g, 5.5 mmol),
2-chloroethyl phenyl sulfide (1.15 g, 6.6 mmol), Na2CO3 (0.88 g, 8.3 mmol), NaI (0.83 g, 5.5 mmol), and
tetrabutylammonium bromide (TBAB) (0.89 g, 2.8 mmol) in dioxane (25 mL) was refluxed for 72 h under
argon atmosphere. After removal of inorganic precipitates by filtration, the residual oil was concentrated in
vacuo, and the residue after dilution with H2O was extracted with CHCl3. The residual oil was chromatographed
with hexane/ethyl acetate (1:2) to give 4a (0.38 g, 15%). Further elution with MeOH gave 3a (1.4 g, 80%).
N-[2-(3,4-Dimethoxyphenyl)ethyl]-2-phenylsulfanylethylamine (3a): Pale yellow oil. IR (film): 3312, 1518.
1H-NMR (90 MHz): 1.73 (1H, br s, >NH), 2.7-3.1 (8H, m, ArCH2CH2-, PhSCH2CH2-), 3.86 (6H, s, OCH3x2),
6.7-6.8 (3H, m, ArH), 7.1-7.4 (5H, m, PhH). 13C-NMR (22.5 MHz): 34.0 (t), 35.7 (t), 48.0 (t), 50.6 (t), 55.7 (q),
55.8 (q), 111.3 (d), 111.9 (d), 120.4 (d), 126.0 (d), 128.7 (dx2), 129.5 (dx2), 132.3 (s), 135.6 (s), 147.4 (s),
148.8 (s). LR-MS m/z: 317 (M+, 4), 137 (100). HR-MS m/z (M+): Calcd for C18H23NO2S: 317.1449. Found:
317.1484.
N-[2-(3,4-Dimethoxyphenyl)ethyl]-di[2-(phenylsulfanyl)ethyl]amine (4a): Yellow gum. IR (film): 1518.
1H-NMR (90 MHz): 2.6-3.1 (12H, m, ArCH2CH2-, PhSCH2CH2-x2), 3.85, 3.86 (each 3H, s, OCH3x2), 6.6-6.9

(3H, m, ArH), 7.0-7.4 (10H, m, PhHx2). 13C-NMR (22.5 MHz): 31.6 (tx2), 33.6 (t), 53.3 (tx2), 55.8 (qx2), 56.3
(t), 111.3 (d), 112.2 (d), 120.5 (d), 125.8 (dx2), 128.8 (dx4), 129.0 (dx4), 132.8 (s), 136.3 (sx2), 147.3 (s), 148.8
(s). FAB-LRMS m/z: 454 (MH+, 28), 137 (100). HR-MS m/z (M+): Calcd for C26H31NO2S2: 453.1796. Found:
453.1799.
N-(2-Phenylethyl)-2-phenylsulfanylethylamine (3b): From 2-phenylethylamine (2b) (8 g, 66 mmol),
2-chloroethyl phenyl sulfide (12.0 g, 72.8 mmol), Na2CO3 (10.6 g, 100 mmol), NaI (10.0 g, 66 mmol), and
TBAB (5.4 g, 33 mmol) in dioxane (200 mL); column chromatography (hexane/ethyl acetate 1:4) gave 3b (10.7
1
g, 63%) as pale yellow oil; IR (film): 3303, 1583. H-NMR (90 MHz): 1.54 (1H, br s, >NH), 2.6-3.2 (8H, m,
PhCH2CH2-, PhSCH2CH2-), 6.9-7.5 (10H, m, PhHx2). 13C-NMR (75 MHz): 34.1 (t), 36.3 (t), 48.1 (t), 50.7 (t),
126.16 (d), 126.20 (d), 128.4 (dx2), 128.7 (dx2), 128.9 (dx2), 129.7 (dx2), 135.6 (s), 139.8 (s). CI-MS m/z: 258
(MH+, 100). HR-MS m/z (M+): Calcd for C16H19NS: 257.1236. Found: 257.1219.
N-(2-Phenylethyl)-di[2-(phenylsulfanyl)ethyl]amine (4b): Elution of hexane/ethyl acetate (20:1) gave 4b (1.5
1
g, 6%) as yellow oil. IR (film): 1583. H-NMR (90 MHz): 2.5-3.2 (12H, m, PhCH2CH2-, PhSCH2CH2-x2),
13
6.9-7.5 (10H, m, PhHx2). C-NMR (22.5 MHz): 31.6 (tx2), 34.0 (t), 53.4 (tx2), 56.1 (t), 125.9 (dx2), 126.0
(dx2), 128.3 (dx2), 128.6 (dx2), 128.8 (dx3), 129.1 (dx4), 136.3 (sx2), 140.1 (s). CI-MS m/z: 394 (MH+, 100).
HR-MS m/z (M+): Calcd for C24H27NS2: 393.1585. Found: 393.1586.
Formylation of 3. Typical Procedure.
To a solution of 3a (11 g, 34.7 mmol ) in formic acid (10 mL) was
added slowly the mixed anhydride prepared from formic acid (25 mL, 0.66 mol) and acetic anhydride (33 mL,
0.35 mol) at 0 °C, and the mixture was heated at 60°C for 1 h. The reaction mixture was concentrated in vacuo
and extracted with CHCl3. The residue was chromatographed with CHCl3 to give 5a (11.9 g, 99%) as yellow
gum.
N-[2-(3,4-Dimethoxyphenyl)ethyl]-N-(2-phenylsulfanylethyl)formamide (5a): IR (film): 1671, 1518.
1H-NMR (90 MHz): 2.6-3.7 (8H, m, ArCH2CH2-, PhSCH2CH2-), 3.85 (6H, s, OCH3x2), 6.5-6.8 (3H, m, ArH),
7.2-7.4 (5H, m, PhH), 7.83, 8.00 (total 1H, each s, CHO). LR-MS m/z: 345 (M+, 7), 164 (100). HR-MS m/z

(M+): Calcd for C19H23NO3S: 345.1399. Found: 345.1407.
N-(2-Phenylethyl)-N-(2-phenylsulfanylethyl)formamide (5b): From 3b (8.5 g, 33.1 mmol); column
chromatography (hexane/ethyl acetate 5:4) gave 5b (9.3 g, 99 %) as yellow gum. IR (film): 1668. 1H-NMR (90
MHz): 2.6-3.7 (8H, m, PhCH2CH2-, PhSCH2CH2-), 6.9-7.6 (10H, m, PhHx2), 7.82, 7.99 (total 1H, eachs,CHO).
LR-MS m/z: 285 (M+, 6), 136 (100). HR-MS m/z (M+): Calcd for C17H19NOS: 285.1186. Found: 285.1216.
Oxidation of 5a with NaIO4. Typical Procedure. A solution of 5a (5 g, 14.5 mmol) and NaIO4 (4.65 g, 21.75
mmol) in MeOH (60 mL) and H2O (30 mL) was stirred at rt for 1.5 h. After removal of inorganic precipitates by
filtration, the filtrate was concentrated in vacuo. The residue was extracted with CHCl3. The product was
chromatographed with hexane/ethyl acetate (1:2) to give 6a (4.9 g, 93%) as yellow gum.
N-[2-(3,4-Dimethoxyphenyl)ethyl]-N-(2-phenylsulfinylethyl)formamide (6a): IR (film): 1669, 1518.
1H-NMR (90 MHz): 2.7-3.8 (8H, m, ArCH2CH2-, PhS(O)CH2CH2-), 3.86 (6H, s, OCH3x2), 6.6-6.9 (3H, m,
ArH), 7.4-7.7 (5H, m, PhH), 7.81, 8.10 (total 1H, each s, CHO). CI-MS m/z: 362 (MH+, 91). HR-MS m/z (M+):
Calcd for C19H23NO4S: 361.1347. Found: 361.1347.
N-(2-Phenylethyl)-N-(2-phenylsulfinylethyl)formamide (6b): From 5b (9 g, 31.6 mmol); column
chromatography (hexane/ethyl acetate 2:1) gave 6b (8.7 g, 92%) as yellow gum. IR (film): 1668. 1H-NMR (90
MHz): 2.6-3.8 (8H, m, Ph-CH2CH2-, PhS(O)-CH2CH2-), 7.0-7.7 (10H, m, PhHx2), 7.78, 8.10 (total 1H, each s,
CHO). CI-MS m/z: 302 (MH+, 92). HR-MS m/z (M+): Calcd for C17H19NO2S: 301.1137. Found: 301.1173.
Pummerer Reaction of 6a.
i) Method A: TFAA (580 mg, 2.76 mmol) in benzene (5 mL) was added to a solution of 6a (200 mg, 0.55
mmol) in benzene (15 mL) at rt under argon atmosphere, and the mixture was stirred for 24 h at the same
temperature. After concentration of the mixture in vacuo, the residue was chromatographed with hexane/ethyl
acetate (3:1) to give 7a (153 mg, 80%) as pale yellow gum.
ii) Method B: A solution of TFAA (1.45 g, 6.9 mmol) in benzene (5 mL) was added to a solution of 6a (500 mg,
1.39 mmol) at rt under argon atmosphere, and the mixture was stirred for 30 min. To this mixture was added

BF3•Et2O (600 mg, 4.2 mmol) and the mixture was further stirred at rt for 1.5 h. After concentration of the
mixture in vacuo, the residue was treated with 5% NaHCO3, and extracted with CHCl3. The product was
chromatographed with hexane/ethyl acetate (3:1) to give 7a (300 mg, 63%).
3-Formyl-7,8-dimethoxy-1-phenylsulfanyl-2,3,4,5-tetrahydro-1H-3-benzazepine (7a): IR (film): 1667,1520.
1H-NMR (90 MHz): 2.6-4.7 (7H, m, H-1, 2, 4, 5), 3.64, 3.72, 3.87 (total 6H, each s, OCH3x2), 6.31, 6.45, 6.62,
6.65 (total 2H, each s, H-6, 9), 7.1-7.5 (5H, m, PhH), 7.95, 8.17 (total 1H, each s, CHO). LR-MS m/z: 343 (M+,
10), 206 (100). HR-MS m/z (M+): Calcd for C19H21NO3S: 343.1243. Found: 343.1265.
Pummerer Reaction of 6b.
i) Method A: TFAA (719 mg, 3.42 mmol) in benzene (5 mL) was added to a solution of 6b (206 mg, 0.68
mmol) at rt under argon atmosphere, and the mixture was stirred for 48 h at the same temperature. After
concentration of the mixture in vacuo, the residue was chromatographed with hexane/ethyl acetate (5:1) to give
8b (47 mg, 36%) as pale yellow gum.
N-(2-Phenylethyl)-N-(2,2-diphenylsulfanylethyl)formamide (8b)
IR (film): 1673. 1H-NMR (90 MHz): 2.5-2.9 (2H, m, PhCH2CH2-), 3.3-3.8 (4H, m,PhCH2CH2-,(PhS)2CHCH2-),
4.27, 4.89 (total 1H, each t, J=7 Hz, (PhS)2CHCH2-), 6.9-7.6 (15H, m, PhHx3), 7.81, 8.04 (total 1H, each s,
CHO). CI-MS m/z: 394 (MH+, 19), 284 (100). HR-MS m/z (M+): Calcd for C23H23NOS2: 393.1218. Found:
393.1207.
ii) Method B: TFAA (1.74 g, 8.3 mmol) in benzene (5 mL) was added to a solution of 6b (500 mg, 1.66 mmol)
at rt under argon atmosphere, and the mixture was stirred for 30 min. To the mixture was added BF3•Et2O (700
mg, 5 mmol) and the mixture was further stirred at rt for 1.5 h. After concentration of the mixture in vacuo, the
residue was basified with 5% NaHCO3, and extracted with CHCl3. The product was chromatographed with
hexane/ethyl acetate (5:1) to give 8b (37 mg, 9%), 5b (41 mg, 11%), and 7b. Further purification of the crude
7b by MPLC with hexane/ethyl acetate (5:1) gave 7b (220 mg, 47%) as colorless gum.
3-Formyl-1-phenylsulfanyl-2,3,4,5-tetrahydro-1H-3-benzazepine (7b): IR (film): 1668. 1H-NMR (90 MHz):

2.6-4.8 (7H, m, H-1, 2, 4, 5), 6.8-7.5 (9H, m, H-6, 7, 8, 9, PhH), 7.98, 8.19 (total 1H, each s, CHO). LR-MS
m/z: 283 (M+, 3), 115 (100). HR-MS m/z (M+): Calcd for C17H17NOS: 283.1031. Found: 283.1068.
Reductive Desulfurization of 7a. General Procedure. To a stirred solution of 7 (a or b) (1 mol eq)
NiCl2•6H2O (7 mol eq) in MeOH-THF (3:1) was added NaBH4 (21 mol eq) by portions at 0°C. After the
addition was complete, stirring was continued at rt for 20 min. The reaction mixture was filtered and the filtrate
was concentrated in vacuo. The products were purified by column chromatography.
3-Formyl-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepine (9a): From 7a (218 mg, 0.64 mmol); column
chromatography (hexane/CHCl3 1:2) gave 9a (131 mg, 88%) as colorless prisms from Et2O, mp 101-103 °C.IR:
1665. 1H-NMR (300 MHz): 2.8-2.9 (4H, m, H-1, 5), 3.46, 3.66 (each 2H, each t, J=5 Hz, H-2, 4), 3.87 (6H, s,
OCH3x2), 6.66, 6.69 (each 1H, s, H-6, 9), 8.14 (1H, s, CHO). LR-MS m/z: 235 (M+, 100). Anal. Calcd for
C13H17NO3: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.58; H, 7.35; N, 5.88.
3-Formyl-2,3,4,5-tetrahydro-1H-3-benzazepine (9b): From 7b (200 mg, 0.7 mmol); column chromatography
(hexane/ethyl acetate 2:3) gave 9b (95 mg, 77%) as colorless plates from Et2O, mp 71-73 °C. IR: 1654.
1H-NMR: 2.7-3.0 (4H, m, H-1, 5), 3.3-3.8 (4H, m, H-2, 4), 7.0-7.4 (2H, m, H-6, 7, 8, 9), 8.14 (1H, s, CHO).
LR-MS m/z: 175 (M+, 59), 117 (100). Anal. Calcd for C11H13NO: C, 75.40; H, 7.48; N, 7.99. Found: C, 75.36; H,
7.35; N, 7.93.
Hydrolysis of 9a. Typical Procedure. A solution of 9a (207 mg, 0.88 mmol) in EtOH (10 mL) and 10%
NaOH (10 mL) was refluxed for 1 h. The mixture was concentrated in vacuo, and the residue after diluted with
H2O was extracted with CHCl3. The product was recrystallized from Et2O to give 10a (147 mg, 81%) as
colorless prisms, mp 93-95 °C (lit.,7 mp 94-95 °C).
1
7,8-Dimethoxy-2,3,4,5-terahydro-1H-3-benzazepine (10a): IR: 3550, 1520. H-NMR (300 MHz): 1.99 (1H,
br s, >NH), 2.8-2.9 (4H, m, H-1, 5), 2.9-3.0 (4H, m, H-2, 4), 3.85, 3.86 (each 3H, s, OCH3x2), 6.64 (2H, s, H-6,
9). 13C-NMR: 39.9 (tx2), 48.8 (tx2), 56.0 (qx2), 113.4 (dx2), 134.4 (sx2), 146.5 (sx2). LR-MS m/z: 207 (M+,71),
165 (100). HR-MS m/z (M+): Calcd for C12H17NO2: 207.1257. Found: 207.1249.

2,3,4,5-Terahydro-1H-3-benzazepine (10b): From 9b (200 mg, 1.14 mmol); column chromatography
(CHCl3/MeOH 9:1) gave 10b (130 mg, 77%) as colorless prisms from Et2O-hexane, mp 157-159 °C (lit.,8 bp 18
1
126-127 °C). IR: 3272. H-NMR (90 MHz): 1.82 (1H, br s, >NH), 2.60 (8H, s, H-1, 2, 4, 5), 6.6-7.0 (4H, m,
H-6, 7, 8, 9). 13C-NMR: 40.3 (tx2), 48.6 (tx2), 126.1 (dx2), 129.2 (dx2), 142.3 (sx2). LR-MS m/z: 147 (M+, 98),
117 (100). HR-MS m/z (M+): Calcd for C10H13N: 147.1046. Found: 147.1046.
Reduction of 9a with LiAlH4. Typical Procedure. LiAlH4 (50 mg, 1.3 mmol) was added to a solution of 9a
(150 mg, 0.64 mmol) in dry THF (30 mL) under ice-cooling, and the mixture was refluxed for 1 h. Et2O
saturated with water was added to the reaction mixture, and insoluble material was filtered off. The product was
chromatographed with CHCl3/ethyl acetate (1:1) to give 11a (71 mg, 50%) as colorless prisms from hexane, mp
37-39 °C (lit.,9 mp 262-263 °C as HCl salt).
1
7,8-Dimethoxy-3-methyl-2,3,4,5-terahydro-1H-3-benzazepine (11a): IR: 1517. H-NMR: 2.37 (3H, s,
>NCH3), 2.4-2.7 (4H, m, H-1, 5), 2.7-3.0 (4H, m, H-2, 4), 3.85 (6H, s, OCH3x2), 6.64 (2H, s, H-6, 9).
13C-NMR: 36.1 (tx2), 47.5 (q), 56.0 (qx2), 57.7 (tx2), 113.0 (dx2), 134.1 (sx2), 146.8 (sx2). LR-MS m/z: 221
(M+, 69), 165 (100). HR-MS m/z (M+): Calcd for C13H19NO2: 221.1416. Found: 221.1417.
3-Methyl-2,3,4,5-terahydro-1H-3-benzazepine (11b): From 9b (400 mg, 2.3 mmol); column chromatography
1
(ethyl acetate) gave 11b (300 mg, 82%) as colorless gum. IR (film): 1494. H-NMR (90 MHz): 2.37 (3H, s,
13
>NCH3), 2.4-2.7 (4H, m, H-1, 5), 2.7-3.2 (4H, m, H-2, 4), 7.0-7.3 (4H, m, H-6, 7, 8, 9). C-NMR: 36.5 (tx2),
47.5 (q), 57.4 (tx2), 126.2 (dx2), 128.8 (dx2), 141.9 (sx2). FAB-LRMS m/z: 162 (MH+, 100). FAB-HRMS m/z
(MH+): Calcd for C11H16N: 162.1283. Found: 162.1284.
ACKNOWLEDGMENT
This work was supported by a Grant-in-Aid for Scientific Research (No 11672115) from the Ministry of
Education, Science, Sports and Culture of Japan.
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MeO
MeO
MeO
Pummerer reaction
N
O
Me
N
O
Me
N
O
Me
MeO
MeO
MeO
MeS
MeS
O
13
12
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