Electrooxidative cyclization of hydroxyamino compounds possessing a benzyl group

Article abstract of DOI:10.1055/s-0031-1290755

Several novel 2-aryl-1,3-oxazinane and 2-aryl-1,3-oxazolidine derivatives were synthesized from N-benzyl-2-piperidineethanols and N-benzyl-2- piperidinemethanols, respectively, by using electrooxidative methods in methanol. For these reactions, the yields of the corresponding cyclized compounds were significantly increased by using catalytic amounts of iodide ions. In contrast, 3-dialkylamino-1-phenylpropanols afforded the expected cyclic 6-phenyl-1,3-oxazinane derivatives using only a small excess of base. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290755

PAPER
▌1315
paper
Electrooxidative Cyclization of Hydroxyamino Compounds Possessing a
Benzyl Group
Electrooxidative Cyclization of Hydroxyamino Compounds
Mitsuhiro Okimoto,* Kousuke Ohashi, Haruki Yamamori, Shinnosuke Nishikawa, Masayuki Hoshi, Takashi Yoshida
Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Kitami, Koen-cho, Hokkaido 090-8507, Japan
Fax +81(0157)247719; E-mail: okimotmt@mail.kitami-it.ac.jp
Received: 19.01.2012; Accepted after revision: 20.02.2012
conditions to give 2-aryl-1,3-oxazolidine (2; n = 1) and 2-
Abstract: Several novel 2-aryl-1,3-oxazinane and 2-aryl-1,3-oxa-
aryl-1,3-oxazinane (2; n = 2) derivatives, respectively
zolidine derivatives were synthesized from N-benzyl-2-piperi-
(Scheme 2).
dineethanols and N-benzyl-2-piperidinemethanols, respectively, by
using electrooxidative methods in methanol. For these reactions, the
yields of the corresponding cyclized compounds were significantly
increased by using catalytic amounts of iodide ions. In contrast, 3-
dialkylamino-1-phenylpropanols afforded the expected cyclic 6-
phenyl-1,3-oxazinane derivatives using only a small excess of base.
– 2 e–, – 2 H+
electrooxidation
N
N
n
n
OH
O
60–67%
Key word: amino alcohols, bicyclic compounds, cyclization, het-
erocycles, oxidation, iodine, benzylation
n = 1 or 2
1
2
Scheme 2
Electrooxidative cyclization of N-benzylpiperidine al-
cohols 1
Electrooxidation is well known as an extremely useful and
attractive method for the oxidation of various organic
compounds.1 Electrooxidation often provides specific
and/or unique reaction products that are difficult to obtain
using typical chemical reagents.2 Our studies focused on
the electrooxidation of nitrogenous organic compounds,
such as amines, enamines, and hydrazones, not only from
the viewpoint of synthesis, but also to study the reactivi-
ties of the substrates.3 We have previously reported on the
indirect electrooxidation of tetrahydroisoquinolyl alco-
hols A in the presence of potassium iodide and a base in
methanol4 in which the oxygen atom of the hydroxy group
selectively attacked the benzylic carbon to yield the corre-
sponding cyclic compound B without any cyclic com-
pound C, as illustrated in Scheme 1.
Accordingly, as described in the present study, electroox-
idative cyclizations of N-benzylpiperidine alcohols 1 (n =
1 and 2) were carried out in the presence of a catalytic
amount of potassium iodide and a base in methanol to af-
ford the expected cyclic compound 2. Similarly, the elec-
trooxidation of 3-dialkylamino-1-phenylpropanols
6
under similar reaction conditions (in the presence of a
strong base in MeOH) gave the corresponding cyclic com-
pounds such as 6-phenyl-1,3-oxazinane derivatives 7, as
shown in Scheme 3.
OH
– 2 e–, – 2 H+
O
R1
R2
N
R2
R1
electrooxidation
R1, R2 = alkyl
N
6
7
N
n
Scheme 3
ylpropanols 6
Electrooxidative cyclization of 3-dialkylamino-1-phen-
O
N
B
electrooxidation
62% (n = 1, 6.2 F·mol–1
73% (n = 2, 7.8 F·mol–1
)
)
n
A
HO
Although there are a few reports that describe the synthe-
sis and/or conformational analysis of these compounds, to
the best of our knowledge, the application of electrooxida-
tion for the preparation of these compounds has yet to be
reported.5
O
tetrahydroisoquinolyl alcohols
n
N
not detected
C
Scheme 1 Electrooxidative cyclization of tetrahydroisoquinolyl al-
cohols A
Initially, optimal reaction conditions for the electrooxida-
tion of 1 were determined using N-benzyl-2-piperi-
dineethanol (1e) as
a model substrate. Various
Based upon the selectivity of the above reaction, we rea-
soned that N-benzylpiperidine (1), possessing a hydroxy
group (n = 1 or 2), should cyclize under electrooxidative
combinations of the supporting electrolytes (mediators
and bases) along with the corresponding yields of the re-
sulting cyclized product (2e) are listed in Table 1. When
either NaOMe or KI was used alone, the yield of 2e was
only 35 and 40%, respectively (Table 1, entries 1 and 2).
Remarkably, the presence of both KI (0.25 equiv to sub-
strate) and NaOMe (0.63 equiv) was effective in increas-
SYNTHESIS 2012, 44, 1315–1322
Advanced online publication: 30.03.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290755; Art ID: SS-2012-F0070-OP
© Georg Thieme Verlag Stuttgart · New York

1316
M. Okimoto et al.
PAPER
ing the yield of 2e to 57% (Table 1, entry 3). The yield was of compound 1 (n = 1 and 2), the substituent effects at the
further increased to nearly 70% by using a small excess of para-position of the benzene ring did not affect the yields
NaOMe (1.25 equiv; Table 1, entry 4). Although the use of 2.
of a strong base such as t-BuOK was similarly effective
(69% yield; Table 1, entry 6), the use of a weak base such
as AcONa decreased the yield of 2e (Table 1, entry 5). In
Table 2 Electrooxidative Cyclization of N-Benzylpiperidine Alco-
holsa
contrast, substitution of KI (Table 1, entry 4) with KCl
(Table 1, entry 7) or KBr (entry 8) resulted in lower yields
of 2e (31 and 37%, respectively). These results indicate
that the yield of 2e is strongly affected by the presence of
KI.
– 2 e–, – 2 H+
electrooxidation
N
N
n
n
OH
O
n = 1 or 2
R
R
1
2
Table 1 Effect of Mediator and Base on the Yields of 2ea
Substrate 1
R
H
n
Current passed Isolated yield
(F·mol–1)
of 2 (%)
– 2 e–, – 2 H+
electrooxidation
N
N
a
b
c
d
e
f
1
1
1
1
2
2
2
2
3.8
3.9
3.7
3.7
6.2
5.3
4.9
5.4
60
62
61
60
65
66
63
67
HO
O
Me
MeO
Cl
1e
2e
Entry
Supporting electrolyte
(mmol)
Recovery of Yield of
1e (%)b
2e (%)b
H
1
2
3
4
5
6
7
8
NaOMe
5
3
35
40
57
69
38
69
31
37
Me
MeO
Cl
KI
2
trace
trace
trace
trace
trace
48
g
h
KI/NaOMe
KI/NaOMe
KI/NaOAc
KI/t-BuOK
KCl/NaOMe
KBr/NaOMe
2/5
2/10
5/10
5/10
2/10
2/10
a Reaction conditions: 1 (8 mmol), KI (2 mmol), NaOMe (10 mmol),
MeOH (40 mL), constant current: 0.3 A, anode: Pt, cathode: Ni, reac-
tion temperature: ca. 5 °C.
In contrast, the electrooxidation of N-ethylphenyl- and N-
propylphenyl-2-piperidineethanols, which do not possess
a benzylic carbon that is directly connected to the nitrogen
atom to form the conjugate system, did not selectively
form the corresponding cyclic compounds. GC analysis
revealed multiple peaks, indicating unselective electroox-
idation.
59
a Reaction conditions: 1e (1.76 g, 8 mmol), MeOH (40 mL), constant
current: 0.3 A, current passed: 6.2 F·mol–1, anode: Pt, cathode: Ni, re-
action temperature: ca. 5 °C.
b Determined by GC analysis.
It is noteworthy that a chemical reaction of 1d with excess
iodine (1.5 equiv) as the oxidant gave less than 10% yield
of 2d in spite of extended reaction times (6 h) and elevated
temperature (50 °C).
From the start of the electrooxidation reaction, the yield of
2e was proportional to the amount of current passed – spe-
cifically, 34% after 3.0 F·mol–1, and then 67% after
6.0 F·mol–1. However, as the reaction proceeded, the cur-
rent efficiency gradually decreased to 66% after
8.0 F·mol–1, therefore, the amount of current passed was
deemed to be sufficient to consume most of 1e. Subse-
quently, these optimal reaction conditions were used to
carry out the electrooxidations of N-benzyl-2-piperidine-
methanols 1a–d and substituted N-benzyl-2-piperi-
dineethanols 1f–h to form 1,3-oxazolidines 2a–d and 1,3-
oxazinanes 2f–h, respectively, as listed in Table 2. Com-
position of the anolyte was monitored by GC analysis. Al-
though the consumption of N-benzyl-2-piperidine-
methanols 1a–d was faster than N-benzyl-2-piperidine-
ethanols 1e–h, the yields of products 2a–d were lower
than those of 2e–h. The lower yields can be attributed to
differences in the structural strain between the five- and
six-membered rings of the cyclic products. In both types
On the other hand, interestingly, our investigations indi-
cated that the amino alcohols do not necessarily require a
benzyl group for intramolecular cyclization, as shown in
Scheme 4.
The electrooxidations of 2-benzyl(methyl)aminoethanol
(3) under similar conditions afforded a nearly equimolar
mixture (51:49) of 2-pheny-3-methyl-1,3-oxazolidine (4)
and 3-benzy-1,3-oxazolidine (5) in a total yield of 78%
(determined by GC analysis). However, the separation of
4 and 5 by either column chromatography or distillation
was not successful due to the similarities in their proper-
ties. Nonetheless, the IR spectra of the mixture of 4 and 5
confirmed the disappearance of the hydroxy group of 3
with the presence of the corresponding ether bond, and
HRMS analysis indicated that both compounds possess
Synthesis 2012, 44, 1315–1322
© Georg Thieme Verlag Stuttgart · New York

PAPER
Electrooxidative Cyclization of Hydroxyamino Compounds
1317
Table 3 Effect of the Supporting Electrolytes on the Yield of 7da
O
HO
N
O
N
N
– 2 e–, – 2 H+
OH
Me
Me
– 2 e–, – 2 H+
+
O
N
electrooxidation
KI/NaOMe
(2–10 mmol)
5.1 F·mol–1
electrooxidation
N
6d
7d
3
4
5
(8 mmol)
yield 78% (4/5 = 51:49)
Entry
Supporting electrolyte
(mmol)
Recovery of Yield of
6d (%)b
7d (%)b
Scheme 4 Electrooxidative cyclization of 2-benzyl(methyl)aminoeth-
anols 3
1
2
3
4
5
6
7
8
NaOMe
NaOMe
NaOMe
KI/NaOMe
NaOAc
5
10
20
1
57
trace
trace
41
65
the same formula composition, but with distinct fragment
peaks. The findings demonstrated that not only benzyl,
but also alkyl carbon atoms can undergo intramolecular
attack by the hydroxy group. The unexpected results indi-
cated that a benzylic carbon atom is not necessary for cy-
clization. As a consequence, we had to revise our
understanding of these reactions, and reasoned that 3-di-
alkylamino-1-phenylpropanols that possess a hydroxy
group at their benzylic carbon position, such as 6, can cy-
clize to yield 6-phenyl-1,3-oxazinane derivatives 7, as il-
lustrated in Scheme 5.
64
2/10
49
5
5
5
5
12
21
t-BuOK
NaClO4
2
63
52
10
p-TsON(Et)4
59
12
a Reaction conditions: 6d (1.76 g, 8 mmol), MeOH (40 mL), constant
current: 0.3A, current passed: 3.7 F·mol–1, anode: Pt, cathode: Ni, re-
action temperature: ca. 15 °C.
OH
b Determined by GC analysis.
– 2 e–, – 2 H+
O
R1
R2
N
R2
R1
electrooxidation
N
trooxidation process was applied for the formation of 6-
phenyl-1,3-oxazinane derivatives 7a–c and 7e–h starting
from 3-dialkylamino-1-phenylpropanols 6a–c and 6e–h,
respectively. For these reactions, symmetrical amino moi-
eties (R1CH2 = R2) were employed to avoid the formation
6
7
Scheme 5 Electrooxidative cyclization of 3-dialkylamino-1-phenyl-
propanols 6
As expected, the carbon atom α to the nitrogen atom of 6 of structural isomers. As listed in Table 4, the correspond-
underwent nucleophilic attack by the hydroxy group to ing cyclized products were obtained in moderate to good
form the corresponding cyclized 6-phenyl-1,3-oxazinane yields using only NaOMe as the supporting electrolyte.
derivatives 7. Initially, the most effective supporting elec-
Cyclized products 7a and 7f were obtained in somewhat
trolyte for the electrooxidation of 6 was determined using
low yields from 6a and 6f, respectively. In contrast, de-
1-phenyl-3-piperidinopropanol (6d) as the model sub-
spite the passage of a small amount of current (2.8 F·mol–1),
the highest yield was obtained for the formation of 7g
(82%) starting from a substrate that possesses a hexameth-
strate. The corresponding yields of the resulting cyclized
product (7d) are listed in Table 3.
Surprisingly, the combination of KI and NaOMe (Table 3, yleneimino moiety 6g. In the case of 6e, the correspond-
entry 4), which was effective in the formation of cyclized
ing cyclized product 7e was obtained as an equimolar
compound 2e (Table 1, entry 4), gave the cyclized product mixture of the cis and trans isomers with a yield of 74%.
7d in only 49% yield, with 41% of the starting substrate Passage of electrical current was continued until almost
6d remaining even after the passage of sufficient current. all the starting substrate was consumed. For the reactions
When an excess of only NaOMe was used, without KI, the with low yields, considerable amounts of tar-like material
yield of 2e increased from 57 (Table 3, entry 1) to 65% remained in the distillation flask and/or on the top of the
(entry 2). Likewise, the use of a strong base such as t-
column used for chromatographic cleanup. Although de-
BuOK afforded the product with a yield of 63% (Table 3,
tails of the reaction mechanisms for the two cyclization
entry 6). In contrast, the use of a weak base such as processes remain unclear, their reaction pathway can be
NaOAc (Table 3, entry 5) resulted in the formation of a proposed as illustrated in Scheme 6. Based on the optimal
tar-like material with a combined yield of 33% of the reaction conditions listed in Table 1 and Table 3, the pro-
starting substrate 6d and product 7d. The use of neutral cesses for 1e and 6d are significantly different; the former
salts such as NaClO4 (Table 3, entry 7) or p-TsON(Et)4
reaction proceeds predominately via indirect electrooxi-
(Table 3, entry 8) suppressed the formation of 7d; in these
dation, and the latter reaction principally involves direct
cases a large portion of substrate 6d remained unreacted. electrooxidation. Specifically, in the case of 1e, the iodide
These results indicate that the cyclization of 6 to 7 differs ion from KI would lose two electrons on the anode to form
significantly from that of 1 to 2. Subsequently, our elec- an iodonium ion at the beginning of the reaction. The re-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1315–1322

1318
M. Okimoto et al.
PAPER
Table 4 Electrooxidative Cyclization of 3-Dialkylamino-1-phenylpropanolsa
OH
– 2 e–, – 2 H+
O
R1
R2
N
R1
electrooxidation
R2
N
6
7
R1
R2
Current passed (F·mol–1)
Substrate 6
Isolated yield of 7 (%)
a
b
c
d
e
f
Et
n-Pr
i-Bu
3.0
3.3
3.4
3.7
3.0
3.8
2.8
3.6
56
74
70
62
74
55
82
67
i-Pr
-(CH2)3-
-(CH2)4-
-CH2CH(Me)CH2CH2-
-CH(Me)CH2CH(Me)CH2-
-(CH2)5-
g
h
-CH2OCH2CH2-
a Reaction conditions: 6 (8 mmol), NaOMe (10 mmol), MeOH (40 mL), constant current: 0.3 A, anode: Pt, cathode: Ni; reaction temperature:
ca. 15 °C.
sulting cationic species would attack substrate 1e at the phenylpropanol. Although the yields were moderate, the
lone pair of the nitrogen atom to form iminium cation 1e′, preparation of such cyclized compounds via electrooxida-
followed by elimination of HI to give conjugated cation tion is novel and allowed us to gain insights into their pe-
1e′′, which would undergo an intramolecular nucleophilic culiar behavior. Furthermore, it is important to note that
attack by the oxygen atom of the hydroxy group to give such electrooxidation reactions could be carried out in a
the cyclic product 2e. On the other hand, in the case of 6d, one-pot reaction, under very mild reaction conditions, and
the formation of cation radical 6d′ would involve drawing without the use of any hazardous oxidants.
one electron from the lone pair of the nitrogen atom. The
cation radical would then lose a second electron via de-
N-Benzyl-2-piperidinemethanol and N-benzyl-2-piperidineethanol
protonation to form iminium cation 6d′′, which would
then undergo nucleophilic attack by the oxygen atom of
the hydroxy group to give cyclized product 7d. In both
cases, the presence of a strong base such as NaOMe or t-
BuOK would promote deprotonation during the course of
the reaction.
were prepared from 2-piperidinemethanol and 2-piperidineethanol,
respectively, via standard benzylation reactions using benzyl chlo-
ride and heating to reflux in EtOH for 3–4 h (83–93%).6 The 3-di-
alkyl amino-1-phenylpropanols were prepared by reduction of the
corresponding 3-dialkyl amino-1-phenylpropanones using NaBH4
and heating to reflux in EtOH for 1–2 h (65–92%).7 The 3-dialkyl
amino-1-phenylpropanones were synthesized from 3-chloropropio-
phenone by alkylation of symmetrical amines and heating to reflux
in EtOH for 3–8 h (54–87%).6 Preparative-scale electrooxidations
were carried out in a tall 50-mL beaker equipped with a fine frit cup
In conclusion, our electrooxidation methodology was suc-
cessfully applied for the cyclization reactions of N-ben-
zyl-2-piperidine alcohols and 3-dialkyl amino-1-
I– from KI
I–
– 2 e–
– H+I–
base
– H+
base
N
N
N
N
I+
I
O
HO
OH
O
H
H
H
H
1e
1e'
1e''
2e
H
H
N
H
H
H
H
N
OH
OH
O
– e–, – H+
base
– H+
base
O
– e–
N
N
6d
6d'
6d''
7d
Scheme 6 Proposed reaction pathway for the cyclization of 1e and 6d
Synthesis 2012, 44, 1315–1322
© Georg Thieme Verlag Stuttgart · New York

PAPER
Electrooxidative Cyclization of Hydroxyamino Compounds
1319
as the cathode compartment with a nickel coil cathode, along with
a cylindrical platinum net anode (45-mm height, 25-mm diameter,
mesh).
MS (EI, 70 eV): m/z (%) = 217 (49) [M+], 216 (99), 187 (34), 186
(63), 127 (26), 126 (100) [M+ – C6H4CH3], 119 (34), 98 (25), 91
(37), 41 (28).
HRMS: m/z [M+] calcd for C14H19NO: 217.1467; found: 217.1417.
Synthesis of 1e; Typical Procedure (Table 2)
A solution of N-benzyl-2-piperidineethanol (1.76 g, 8 mmol) in
MeOH (40 mL) containing KI (0.33 g, 2 mmol) and NaOMe (10
mmol) was subjected to electrooxidation under a constant current
(0.3 A) with magnetic stirring at ca. 5 °C. The course of the electro-
oxidation was monitored by GC analysis (FFAP 10%-Chromosorb
W AW, 1.5 m). The passage of electric current was continued until
almost all the substrate had been consumed. After passage of the
electrolytic current (6.2 F·mol–1), the reaction mixture was concen-
trated (ca. 10 mL) in vacuo at approximately 50 °C, then extracted
using Et2O (3 × 40 mL) without use of water. The resulting, slightly
cloudy ether solution was dried over Na2SO4 overnight and then fil-
tered. After removal of the solvent in vacuo, the cyclized products
were isolated by reduced pressure distillation and/or silica gel col-
umn chromatography (350-mm height, 28-mm diameter; Et2O–hex-
ane, 1:1).
3-(4-Methoxyphenyl)hexahydro-1H-oxazolo[3,4-a]pyridine
(2c)
Yield: 1.14 g (61%); white fine needle-like crystals (from EtOH);
mp 30–31 °C (EtOH); Rf = 0.54 (Et2O–n-hexane, 1:1).
IR (KBr): 2943 (s), 1613, 1515, 1300, 1248 (s), 1169, 1092, 1026
(s), 825, 807 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.22–1.42 (m, 2 H), 1.44–1.56 (m,
1 H), 1.58–1.65 (m, 1 H), 1.78–1.87 (m, 2 H), 1.95–2.05 (m, 1 H),
2.43–2.51 (m, 1 H), 2.64–2.72 (m, 1 H), 3.61–3.67 (m, 1 H), 3.79
(s, 3 H, CH3O), 4.00–4.06 (m, 1 H), 4.55 (s, 1 H), 6.88 (d, J = 8 Hz,
2 H, ArH), 7.38 (d, J = 8 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): δ = 23.57 (CH2), 24.80 (CH2), 27.03
(CH2), 47.17 (CH2), 55.23 (CH3O), 67.75 (CH), 71.08 (CH2), 96.34
(CH), 113.61 (CH), 129.25 (CH), 131.30 (C), 160.12 (C).
MS (EI, 70 eV): m/z (%) = 233 (26) [M+], 232 (100), 203 (14), 202
(32), 135 (28), 126 (56) [M+ – C6H4OCH3], 121 (15), 119 (5), 96
(5), 79 (9), 41 (7).
Synthesis of 6d; Typical Procedure (Table 4)
A solution of 3-piperidino-1-phenylpropanol (1.76 g, 8 mmol) in
MeOH (40 mL) containing NaOMe (10 mmol) was subjected to
electrooxidation under a constant current (0.3 A) at ca. 15 °C with
magnetic stirring. After passage of the electrolytic current (3.7
F·mol–1), the reaction mixture was concentrated (ca. 10 mL) in vac-
uo at approximately 50 °C. The resulting residue was treated with
H2O (20 mL) and then extracted with Et2O (3 × 40 mL). The com-
bined ether layers were dried over Na2SO4 overnight. After removal
of the solvent in vacuo, the cyclized products were isolated by re-
duced pressure distillation (in the case of 7a and 7b) or silica gel
column chromatography (350-mm height, 28-mm diameter; EtO-
Ac–EtOH, 3:1).
HRMS: m/z [M+] calcd for C14H19NO2: 233.1416; found: 233.1471.
3-(4-Chlorophenyl)hexahydro-1H-oxazolo[3,4-a]pyridine (2d)
Yield: 1.14 g (60%); white powder (from EtOH); mp 36–37 °C
(EtOH); Rf = 0.66 (Et2O–n-hexane, 1:1).
IR (KBr): 2939 (s), 2804, 1492, 1363, 1089 (s), 1023, 1015, 841,
823, 807 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.18–1.40 (m, 2 H), 1.42–1.55 (m,
1 H), 1.58–1.72 (m, 1 H), 1.75–1.91 (m, 2 H), 1.97–2.08 (m, 1 H),
2.42–2.54 (m, 1 H), 2.62–2.70 (m, 1 H), 3.62–3.70 (m, 1 H), 4.02–
4.08 (m, 1 H), 4.56 (s, 1 H), 7.32 (d, J = 8 Hz, 2 H, ArH), 7.39 (d,
J = 8 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): δ = 23.49 (CH2), 24.74 (CH2), 26.96
(CH2), 47.09 (CH2), 62.74 (CH), 71.33 (CH2), 95.82 (CH), 128.43
(CH), 129.44 (CH), 134.59 (C), 137.87 (C).
MS (EI, 70 eV): m/z (%) = 239 (17) [M+, 37Cl], 238 (46), 237 (53)
[M+, 35Cl], 236 (85), 208 (43), 207 (46), 206 (61), 139 (43), 127
(43), 126 (100) [M+ – C6H4Cl], 41 (38).
HRMS: m/z [M+] calcd for C13H16NOCl: 237.0920; found:
237.0952.
3-Phenylhexahydro-1H-oxazolo[3,4-a]pyridine (2a)
Yield: 0.98 g (60%); colorless viscous oily liquid; bp 151–
153 °C/2.0 mbar; Rf = 0.68 (Et2O–n-hexane, 1:1).
IR (neat): 2937 (s), 2871, 1456, 1377, 1099, 1078, 1024 (s), 755,
699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.18–1.44 (m, 1 H), 1.46–1.66 (m,
3 H), 1.72–1.86 (m, 2 H), 1.98–2.06 (m, 1 H), 2.44–2.54 (m, 1 H),
2.64–2.74 (m, 1 H), 3.60–3.74 (m, 1 H), 4.04–4.16 (m, 1 H), 4.59
(s, 1 H), 7.18–7.38 (m, 3 H, PhH), 7.39–7.48 (m, 2 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 23.52 (CH2), 24.75 (CH2), 26.59
(CH2), 47.14 (CH2), 62.77 (CH), 71.23 (CH2), 96.62 (CH), 128.00
(CH), 128.18 (CH), 128.84 (CH), 139.18 (C).
MS (EI, 70 eV): m/z (%) = 203 (36) [M+], 202 (73), 173 (34), 172
(60), 126 (100) [M+ – Ph], 105 (39), 98 (24), 91 (51), 77 (29), 65
(13).
1-Phenyloctahydropyrido[1,2-c][1,3]oxazine (2e)
Yield: 1.13 g (65%); white, fine rod-like crystals (from EtOH); bp
113–115 °C/2.7 mbar; mp 53–55 °C (ErOH); Rf = 0.53 (Et2O–n-
hexane, 1:1).
HRMS: m/z [M+] calcd for C13H17NO: 203.1310; found: 203.1318.
IR (KBr): 2934 (s), 2844, 1453, 1369, 1130, 1118, 1083 (s), 755,
670 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.22–1.34 (m, 1 H), 1.38–1.52 (m,
4 H), 1.58–1.76 (m, 3 H), 1.82–1.96 (m, 1 H), 2.20–2.30 (m, 1 H),
2.34–2.44 (m, 1 H), 3.60–3.74 (m, 1 H), 4.06–4.16 (m, 1 H), 4.34
(s, 1 H), 7.22–7.38 (m, 3 H, Ph), 7.38–7.52 (m, 2 H, Ph).
13C NMR (100 MHz, CDCl3): δ = 24.10 (CH2), 25.53 (CH2), 32.42
(CH2), 32.74 (CH2), 49.03 (CH2), 61.41 (CH), 67.82 (CH2), 97.39
(CH), 127.88 (CH), 128.25 (CH), 128.52 (CH), 139.86 (C).
MS (EI, 70 eV): m/z (%) = 217 (4) [M+], 173 (83), 172 (43), 140
(42) [M+ – Ph], 105 (15), 96 (20), 92 (28), 91 (100), 82 (18), 77 (13),
65 (20).
3-p-Tolylhexahydro-1H-oxazolo[3,4-a]pyridine (2b)
Yield: 1.08 g (62%); white powder (from EtOH); mp 48–49 °C
(EtOH); Rf = 0.67 (Et2O–n-hexane, 1:1).
IR (KBr): 2944 (s), 1326, 1196, 1149, 1124, 1090 (s), 1017, 935,
821, 804 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.18–1.42 (m, 2 H), 1.45–1.46 (m,
1 H), 1.57–1.65 (m, 1 H), 1.78–1.86 (m, 2 H), 1.96–2.06 (m, 1 H),
2.34 (s, 3 H, CH3), 2.43–2.52 (m, 1 H), 2.66–2.73 (m, 1 H), 3.62–
6.68 (m, 1 H), 4.01–4.07 (m, 1 H), 4.56 (s, 1 H), 7.15 (d, J = 8 Hz,
2 H, ArH), 7.34 (d, J = 8 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): δ = 21.26 (CH3), 23.56 (CH2), 24.78
(CH2), 26.99 (CH2), 41.18 (CH2), 62.79 (CH), 71.17 (CH2), 96.54
(CH), 127.94 (CH), 128.91 (CH), 136.23 (C), 138.58 (C).
HRMS: m/z [M+] calcd for C14H19NO: 217.1467; found: 217.1436.
1-p-Tolyloctahydropyrido[1,2-c][1,3]oxazine (2f)
Yield: 1.22 g (66%); white powder (from EtOH); mp 66–67 °C
(EtOH); Rf = 0.49 (Et2O–n-hexane, 1:1).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1315–1322

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M. Okimoto et al.
PAPER
IR (KBr): 2934 (s), 2922, 1368, 1255, 1118 (s), 1096, 1081 (s),
1043, 817 cm–1.
HRMS (fragment): m/z [M+ – C6H5] calcd for C4H8NO–: 86.0606;
found: 86.0772.
1H NMR (400 MHz, CDCl3): δ = 1.21–1.34 (m, 1 H), 1.35–1.54 (m,
4 H), 1.56–1.75 (m, 3 H), 1.82–1.95 (m, 1 H), 2.18–2.28 (m, 1 H),
2.33 (s, 3 H, CH3), 2.80–3.45 (m, 1 H), 3.65–3.74 (m, 1 H), 4.07–
4.12 (m, 1 H), 4.30 (s, 1 H), 7.14 (d, J = 8 Hz, 2 H, ArH), 7.34 (d,
J = 8 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): δ = 21.23 (CH3), 24.14 (CH2), 25.55
(CH2), 32.48 (CH2), 32.76 (CH2), 49.12 (CH2), 61.54 (CH), 67.83
(CH2), 97.33 (CH), 127.77 (CH), 128.96 (CH), 136.94 (C), 138.22
(C).
HRMS (fragment): m/z [M+ – 3-methyloxazolidine ring (C4H8NO)]
calcd for C6H5 : 77.0391; found: 77.0398.
–
3-Benzyloxazolidine (5)
MS (EI, 70 eV): m/z (%) = 163 (13) [M+], 162 (36), 118 (12), 105
(11), 92 (33), 91 (100) [C6H5CH2], 86 (18), 72 (49) [M+
C6H5CH2], 65 (24), 42 (35).
–
HRMS: m/z [M+] calcd for C10H13NO: 163.0997; found: 163.0993.
HRMS (fragment): m/z [M+ – C6H5CH2] calcd for C3H6NO–:
MS (EI, 70 eV): m/z (%) = 231 (23)[M+], 230 (32), 187 (64), 140
(79) [M+ – C6H4CH3], 120 (42), 112 (35), 105 (100), 91 (31), 83
(34), 55 (35).
72.0449; found: 72.0541.
HRMS (fragment): m/z [M+ – oxazolidine ring (C3H6NO)] calcd for
–
C7H7 : 91.0548; found: 91.0593.
HRMS: m/z [M+] calcd for C15H21NO: 231.1623; found: 231.1601.
2-Ethyl-6-phenyl-3-propyl-1,3-oxazinane (7a)
Yield: 1.04 g (56%); colorless viscous oily liquid; bp 115–
117 °C/2.7 mbar; Rf = 0.87 (EtOH–EtOAc, 1:3).
1-(4-Methoxyphenyl)octahydropyrido[1,2-c][1,3]oxazine (2g)
Yield: 1.24 g (63%); white, fine needle-like crystals (from EtOH);
mp 88–89 °C; Rf = 0.30 (Et2O–n-hexane, 1:1).
IR (neat): 2963 (s), 2935, 2872, 1452, 1189, 1091 (s), 1071 (s), 962,
752, 698 cm–1.
IR (KBr): 2921 (s), 1615, 1517, 1245 (s), 1175, 1115, 1079 (s),
1030, 831, 821 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.18–1.33 (m, 1 H), 1.37–1.52 (m,
4 H), 1.58–1.76 (m, 4 H), 1.80–1.95 (m, 1 H), 2.17–2.27 (m, 1 H),
2.37–2.44 (m, 1 H), 3.65–3.74 (m, 1 H), 3.78 (s, 3 H, CH3O), 4.28
(s, 1 H), 6.86 (d, J = 8 Hz, 2 H, ArH), 7.37 (d, J = 8 Hz, 2 H, ArH).
1H NMR (400 MHz, CDCl3): δ = 0.92 (t, J = 7.4 Hz, 3 H, CH3), 0.98
(t, J = 7.4 Hz, 3 H, CH3), 1.36–1.61 (m, 3 H), 1.64–1.76 (m, 2 H),
1.88–1.98 (m, 1 H), 2.53–2.70 (m, 2 H), 2.90–3.01 (m, 1 H), 3.17–
3.28 (m, 1 H), 4.20 (t, J = 5.8 Hz, 1 H), 4.52–4.58 (m, 1 H), 7.18–
7.41 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 9.91 (CH3), 12.00 (CH3), 21.52
(CH2), 26.34 (CH2), 28.74 (CH2), 47.74 (CH2), 50.02 (CH2), 79.48
(CH), 94.67 (CH), 125.75 (CH), 127.29 (CH), 128.31 (CH), 143.09
(C).
MS (EI, 70 eV): m/z (%) = 233 (4) [M+], 204 (90), 132 (43), 117
(49), 105 (100), 100 (74), 77 (84), 72 (71), 51 (42), 43 (47).
13C NMR (100 MHz, CDCl3): δ = 24.18 (CH2), 25.59 (CH2), 32.57
(CH2), 32.80 (CH2), 49.18 (CH2), 55.23 (CH3O), 61.58 (CH), 67.80
(CH2), 97.02 (CH), 113.63 (CH), 129.00 (CH), 132.25 (C), 159.74
(C).
MS (EI, 70 eV): m/z (%) = 247 (2) [M+], 246 (3), 203 (18), 140 (7)
[M+ – C6H4OCH3], 136 (9), 135 (6), 122 (10), 121 (100), 92 (4), 77
(5), 76 (6).
HRMS: m/z [M+] calcd for C15H23NO: 233.1780; found: 233.1761.
HRMS: m/z [M+] calcd for C15H21NO2: 247.1572; found: 247.1580.
3-Isobutyl-2-isopropyl-6-phenyl-1,3-oxazinane (7b)
Yield: 1.55 g (74%); colorless viscous oily liquid; bp 126–128 °C/
2.7 mbar; Rf = 0.83 (EtOH–EtOAc, 1:3).
1-(4-Chlorophenyl)octahydropyrido[1,2-c][1,3]oxazine (2h)
Yield: 1.35 g (67%); white, fine rod-like crystals (from EtOH); mp
70–71 °C; Rf = 0.54 (Et2O–n-hexane, 1:1).
IR (neat): 2956 (s), 2927, 2869, 1468, 1453, 1094 (s), 1074, 986,
749, 698 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.85–1.03 (m, 12 H), 1.42–1.48
(m, 1 H), 1.60–2.06 (m, 3 H), 2.22–2.30 (m, 1 H), 2.40–2.57 (m,
1 H), 3.18–3.27 (m, 1 H), 3.83–3.90 (m, 2 H), 4.50–4.58 (m, 1 H),
7.19–7.40 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 18.75 (CH3), 18.96 (CH3), 19.27
(CH3), 19.83 (CH3), 20.55 (CH), 20.67 (CH), 21.16 (CH), 26.21
(CH), 27.54 (CH2), 27.64 (CH2), 29.63 (CH2), 44.57 (CH2), 49.90
(CH2), 52.78 (CH2), 61.68 (CH2), 79.24 (CH), 96.51 (CH), 98.96
(CH), 125.52 (CH), 125.94 (CH), 127.07 (CH), 127.31 (CH),
128.20 (CH), 128.36 (CH), 143.41 (C), 143.49 (C).
IR (KBr): 2924 (s), 2847, 2788, 1367, 1226, 1119, 1083 (s), 1043,
1011, 820 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.18–1.32 (m, 1 H), 1.33–1.53 (m,
4 H), 1.56–1.76 (m, 3 H), 1.80–1.94 (m, 1 H), 2.20–2.30 (m, 1 H),
2.31–2.40 (m, 1 H), 3.64–3.74 (m, 1 H), 4.06–4.13 (m, 1 H), 4.32
(s, 1 H), 7.31 (d, J = 8 Hz, 2 H, ArH), 7.40 (d, J = 8 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): δ = 24.00 (CH2), 25.49 (CH2), 32.23
(CH2), 32.69 (CH2), 48.89 (CH2), 61.26 (CH), 67.81 (CH2), 96.42
(CH), 128.45 (CH), 129.30 (CH), 134.17 (C), 138.49 (C).
MS (EI, 70 eV): m/z (%) = 253 (7) [M+, 37Cl], 251 (19) [M+, 35Cl],
250 (25), 207 (44), 141 (42), 140 (100) [M+ – C6H4Cl], 127 (36),
125 (66), 112 (38), 83 (36), 55 (37).
MS (EI, 70 eV): m/z (%) = 261 (2) [M+], 216 (76), 187 (15), 117
(38), 112 (21), 105 (100), 84 (50), 83 (44), 82 (37), 77 (53).
HRMS: m/z [M+] calcd for C17H27NO: 261.2093; found: 261.2051.
HRMS: m/z [M+] calcd for C14H18NOCl: 251.1077; found:
251.0990.
2-Phenylhexahydro-2H-pyrrolo[2,1-b][1,3]oxazine (7c)
Yield: 1.14 g (70%); slightly yellow viscous oily liquid; Rf = 0.41
(EtOH–EtOAc, 1:3).
Synthesis of a Mixture of 4 and 5
Yield: 0.87 g (67%, GC yield 78%); colorless viscous oily liquid;
bp 185–192 °C/21 mbar; Rf = 0.59 (Et2O–n-hexane, 1:1).
IR (neat): 2943 (s), 2859, 1451, 1348 (s), 1147, 1053 (s), 990, 969,
751, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.19–1.47 (m, 1 H), 1.57–2.18 (m,
5 H), 2.70–2.86 (m, 1 H), 3.05–3.45 (m, 3 H), 4.44–4.59 (m, 1 H),
4.60–4.70 (m, 1 H), 7.09–7.48 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 21.55 (CH2), 27.32 (CH2), 31.92
(CH2), 46.10 (CH2), 47.66 (CH2), 78.61 (CH), 92.01 (CH), 125.85
(CH), 127.43 (CH), 128.36 (CH), 142.78 (C).
IR (neat): 2946, 2884, 2798, 1455, 1055 (s), 1026, 758, 699 (s)
cm–1.
3-Methyl-2-phenyloxazolidine (4)
MS (EI, 70 eV): m/z (%) = 163 (22)[M+], 162 (67), 132 (40), 105
(43), 91 (29), 86 (100) [M+ – C6H5], 77 (32) [C6H5], 58 (22), 51 (13),
42 (15).
HRMS: m/z [M+] calcd for C10H13NO: 163.0997; found: 163.0991.
Synthesis 2012, 44, 1315–1322
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Electrooxidative Cyclization of Hydroxyamino Compounds
1321
MS (EI, 70 eV): m/z (%) = 203 (16) [M+], 132 (47), 105 (100), 97
(71), 84 (79), 83 (46), 77 (90), 51 (52), 43 (47), 42 (46).
HRMS: m/z [M+] calcd for C13H17NO: 203.1310; found: 203.1313.
1H NMR (400 MHz, CDCl3): δ = 1.31–1.88 (m, 9 H), 2.08–2.18 (m,
1 H), 2.38–2.50 (m, 1 H), 3.08–3.24 (m, 3 H), 4.45 (t, J = 7 Hz,
1 H), 4.55 (dd, J = 10, 2.5 Hz, 1 H), 7.15–7.47 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 21.90 (CH2), 29.80 (CH2), 29.90
(CH2), 30.21 (CH2), 34.87 (CH2), 48.90 (CH2), 55.20 (CH2), 79.39
(CH), 92.32 (CH), 112.88 (CH), 127.38 (CH), 128.36 (CH), 143.03
(C).
2-Phenyloctahydropyrido[2,1-b][1,3]oxazine (7d)
Yield: 1.08 g (62%); slightly yellow viscous oily liquid; Rf = 0.60
(EtOH–EtOAc, 1:3).
MS (EI, 70 eV): m/z (%) = 231 (3) [M+], 174 (12), 132 (28), 131
(18), 115 (17), 112 (16), 105 (100), 104 (15), 77 (71), 51 (59).
IR (neat): 2941 (s), 2857, 1451, 1349, 1281, 1145, 1136, 1079 (s),
754, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.33–1.47 (m, 1 H), 1.55–1.90 (m,
6 H), 2.00–2.21 (m, 2 H), 2.48–2.58 (m, 1 H), 2.86–2.96 (m, 1 H),
3.00–3.08 (m, 1 H), 3.64–3.72 (m, 1 H), 4.43–4.50 (m, 1 H), 7.20–
7.42 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 22.51 (CH2), 25.12 (CH2), 31.54
(CH2), 32.75 (CH2), 52.56 (CH2), 53.86 (CH2), 79.57 (CH), 92.75
(CH), 126.03 (CH), 127.53 (CH), 128.37 (CH), 142.30 (C).
HRMS: m/z [M+] calcd for C15H21NO: 231.1623; found: 231.1612.
2-Phenylhexahydro-2H-[1,3]oxazino[2,3-c][1,4]oxazine (7h)
Yield: 1.17 g (67%); colorless viscous oily liquid; Rf = 0.70 (EtOH–
EtOAc, 1:3).
IR (neat): 2921, 2857 (s), 1453, 1343, 1279, 1152, 1131 (s), 1090
(s), 755, 750 cm–1.
MS (EI, 70 eV): m/z (%) = 217 (7) [M+], 132 (45), 131 (23), 111
(24), 105 (100), 104 (25), 98 (32), 84 (31), 77 (75), 51 (26).
HRMS: m/z [M+] calcd for C14H19NO: 217.1467; found: 217.1463.
1H NMR (400 MHz, CDCl3): δ = 1.70–1.82 (m, 1 H), 2.10–2.17 (m,
1 H), 2.39–2.51 (m, 1 H), 2.61–2.74 (m, 1 H), 2.84–2.96 (m, 1 H),
3.00–3.12 (m, 1 H), 3.46–3.58 (m, 1 H), 3.73–3.92 (m, 4 H), 4.49–
4.58 (m, 1 H), 7.21–7.41 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 32.11 (CH2), 50.80 (CH2), 52.91
(CH2), 66.75 (CH2), 69.11 (CH2), 79.60 (CH), 88.93 (CH), 125.92
(CH), 127.74 (CH), 128.43 (CH), 141.69 (C).
8-Methyl-2-phenyloctahydropyrido[2,1-b][1,3]oxazine (7e)
Yield: 1.37 g (74%); colorless viscous oily liquid; Rf = 0.69 (EtOH–
EtOAc, 1:3).
MS (EI, 70 eV): m/z (%) = 219 (15) [M+], 189 (23), 132 (45), 131
(26), 105 (100), 104 (80), 103 (36), 78 (35), 77 (92), 51 (35).
IR (neat): 2948 (s), 2923, 2867, 1452, 1135, 1120, 1089 (s), 1078,
753, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.93 (d, J = 6.4 Hz, 1.5 H,
0.5 × CH3), 0.97 (d, J = 6.4 Hz, 1.5 H, 0.5 × CH3), 1.21–1.28 (m,
1 H), 1.30–1.47 (m, 2 H), 1.52–1.64 (m, 1 H), 1.75–2.18 (m, 4 H),
2.35–2.54 (m, 1 H), 2.98–3.10 (m, 1 H), 3.17–3.27 (m, 1 H), 4.41–
4.64 (m, 2 H), 7.18–7.45 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 21.37 (CH3), 21.85 (CH3), 25.08
(CH), 27.92 (CH2), 30.02 (CH), 33.43 (CH2), 33.69 (CH2), 33.80
(CH2), 38.98 (CH2), 40.06 (CH2), 45.66 (CH2), 52.36 (CH2), 53.24
(CH2), 53.84 (CH2), 79.44 (CH), 79.90 (CH), 87.76 (CH), 93.16
(CH), 125.77 (CH), 126.07 (CH), 127.47 (CH), 127.53 (CH),
128.36 (CH), 128.42 (CH), 142.18 (C), 143.04 (C).
HRMS: m/z [M+] calcd for C13H17NO2: 219.1259; found: 219.1199.
References
(1) (a) Nelson, R. F. Techniques of Electroorganic Synthesis;
Wiley: New York, 1974. (b) Torii, S. Electroorganic
Synthesis; Kodansha: Tokyo, 1985. (c) Okimoto, M.;
Takahashi, Y. Curr. Org. Synth. 2004, 1, 233.
(2) (a) Andreades, S.; Zahnow, E. W. J. Am. Chem. Soc. 1969,
91, 4181. (b) Torii, S.; Inokuchi, T.; Takahashi, N. J. Org.
Chem. 1978, 43, 5020. (c) Miller, L. L.; Hoffmann, A. K.
J. Am. Chem. Soc. 1967, 89, 593. (d) Johnson, D. K.;
Jansson, R. E. W. J. Electrochem. Soc. 1981, 128, 1885.
(e) Okimoto, M.; Numata, K.; Takahashi, Y.; Hoshi, M.;
Tomozawa, K.; Shigemoto, T. Synlett 2005, 2507.
MS (EI, 70 eV): m/z (%) = 231 (7) [M+], 132 (47), 112 (49), 105
(100), 98 (48), 97 (37), 77 (86), 56 (39), 55 (62), 51 (52).
HRMS: m/z [M+] calcd for C15H21NO: 231.1623; found: 231.1616.
7,9-Dimethyl-2-phenyloctahydropyrido[2,1-b][1,3]oxazine (7f)
Yield: 1.08 g (55%); colorless viscous oily liquid; Rf = 0.73 (EtOH–
EtOAc, 1:3).
(f) Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.;
Komata, M.; Numata, K.; Tomozawa, K. Synlett 2006, 1753.
(3) (a) Chiba, T.; Okimoto, M.; Nagai, H.; Takata, Y. J. Org.
Chem. 1979, 44, 3519. (b) Chiba, T.; Okimoto, M.; Nagai,
H.; Takata, Y. J. Org. Chem. 1983, 48, 2968. (c) Okimoto,
M.; Chiba, T. J. Org. Chem. 1990, 55, 1070. (d) Chiba, T.;
Okimoto, M. J. Org. Chem. 1992, 57, 1375. (e) Okimoto,
M.; Takahashi, Y.; Kakuchi, T. Synthesis 2003, 2057.
(f) Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.;
Komata, M.; Tomozawa, K.; Chiba, T. Heterocycles 2008,
75, 35. (g) Okimoto, M.; Numata, K.; Tomozawa, K.;
Shigemoto, T.; Hoshi, M.; Takahashi, Y. Aust. J. Chem.
2005, 58, 560. (h) Okimoto, M.; Takahashi, Y.; Nagata, Y.;
Numata, K.; Sasaki, G. Synth. Commun. 2005, 35, 1989.
(i) Okimoto, M.; Chiba, T. J. Org. Chem. 1988, 53, 218.
(4) Okimoto, M.; Yoshida, T.; Hoshi, M.; Hattori, K.; Komata,
M.; Numata, K.; Tomozawa, K. Heterocycles 2006, 68,
2563.
IR (neat): 2951, 2921, 1454, 1219, 1154, 1142, 1099, 1089 (s), 749,
699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.87 (d, J = 6.4 Hz, 3 H, CH3),
0.97 (d, J = 6.4 Hz, 3 H, CH3), 1.10–1.28 (m, 1 H), 1.69–2.10 (m,
5 H), 2.30–2.42 (m, 1 H), 2.72–2.82 (m, 1 H), 3.01–3.17 (m, 2 H),
3.19–3.75 (m, 1 H), 4.35–4.48 (m, 1 H), 7.19–7.42 (m, 5 H, PhH).
13C NMR (100 MHz, CDCl3): δ = 17.49 (CH3), 19.19 (CH3), 30.08
(CH), 33.41 (CH2), 35.98 (CH), 41.04 (CH2), 54.04 (CH2), 61.65
(CH2), 79.04 (CH), 98.83 (CH), 125.78 (CH), 127.27 (CH), 128.21
(CH), 142.42 (C).
MS (EI, 70 eV): m/z (%) = 245 (6) [M+], 174 (13), 139 (21), 132
(31), 126 (29), 112 (23), 105 (100), 104 (19), 77 (76), 51 (23).
HRMS: m/z [M+] calcd for C16H23NO: 245.1780; found: 245.1780.
(5) (a) Fernández, B.; Carballeira, L.; Ríos, M. A. J. Mol. Struct.
1991, 245, 53. (b) Crabb, T. A.; Newton, R. F. Tetrahedron
1968, 24, 4423. (c) Taguchi, T.; Kasuga, S. Chem. Pharm.
Bull. 1965, 13, 241. (d) Tilford, C. H.; Campen, M. G. V.
J. Am. Chem. Soc. 1954, 76, 2431. (e) Goodson, L. H.;
Christopher, H. J. Am. Chem. Soc. 1950, 72, 358. (f) Azzena,
U.; Pilo, L.; Piras, E. Tetrahedron Lett. 2001, 42, 129.
2-Phenyloctahydro-2H-[1,3]oxazino[3,2-a]azepine (7g)
Yield: 1.52 g (82%); slightly yellow viscous oily liquid; Rf = 0.72
(EtOH–EtOAc, 1:3).
IR (neat): 2934 (s), 2853, 1452, 1354, 1118, 1095 (s), 995, 955, 752,
699 cm–1.
© Georg Thieme Verlag Stuttgart · New York
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