Reactions of unsymmetrical α-diazo-β-diketones with imines: Syntheses of 4H-1,3-oxazin-4-ones

Article abstract of DOI:10.1002/hc.10015

The cycloaddition reactions of an unsymmetrical α-diazo-β-diketone, 2-diazo-1-phenyl-1,3-butanedione, with a series of imines with various substituents were studied. The nuclear magnetic resonance (NMR) spectra, infrared (IR) spectra, and mass spectra stu

Full text of DOI:10.1002/hc.10015

Heteroatom Chemistry
Volume 13, Number 2, 2002
Reactions of Unsymmetrical
-Diazo- -Diketones with Imines:
Syntheses of 4H-1,3-Oxazin-4-ones
Jiaxi Xu and Liangbi Chen
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
Received 2 July 2001; revised 15 August 2001
and thiones [11], as well as electron-rich alkenes or
ABSTRACT: Cycloaddition reactions of an unsym-
alkynes, for example, enamines [11] or enol ethers
[12]. They can also react with some heterocumulenes
[13], such as carbodiimides and isocyanates.
metrical
-diazo- -diketone, 2-diazo-1-phenyl-1,3-
butanedione, with a series of imines having various
substituents were studied. The results indicated that
only cycloadducts derived from acetylphenylketene,
which was generated by the thermal Wolff rear-
Recently, we studied the reactions of ␣-diazo-
␤-diketones with the imine moieties present in 1,5-
benzodiazepines and 1,5-benzothiazepines and
found that the reactive species were actually acetyl-
phenylketene or benzoylmethylketene, generated
from unsymmetrical 2-diazo-1-phenyl-1,3-butane-
dione, and produced, respectively, 1,3-oxazinone
derivatives with methyl and phenyl groups in differ-
ent positions [6,7]. In order to understand the differ-
ences in the reactions, we have now investigated the
reactions of unsymmetrical 2-diazo-1-phenyl-1,3-
butanedione with a series of relatively simple imines.
rangement
of
2-diazo-1-phenyl-1,3-butanedione
with phenyl migration, and imines were obtained.
C
2002 Wiley Periodicals, Inc. Heteroatom Chem
13:165–168, 2002; Published online in Wiley Interscience
(www.interscience.wiley.com). DOI 10.1002/hc.10015
INTRODUCTION
␣-Diazo-␤-diketones, diacyldiazomethanes, are
highly reactive and useful synthons for the synthe-
ses of oxy-containing six-membered heterocyclic
compounds [1–3]. They show a pronounced ten-
dency to undergo a Wolff rearrangement by thermal,
photolytic, or metal catalytic elimination of nitrogen
to generate acylketenes. The acylketenes participate
preferentially as the 4␲ component in inverse
(diene LUMO controlled) Diels–Alder reactions with
electron-rich and/or dipolar dieneophiles [4–9].
They are especially prone to undergo [2 + 4] cy-
cloadditions with heterodienophiles, such as imines
[4–7], nitriles [8], aldehydes and ketones [9,10],
RESULTS AND DISCUSSION
A series of imines 1a–l were obtained by reaction of
aromatic aldehydes with aromatic amines [14,15].
Unsymmetrical 2-diazo-1-phenyl-1,3-butanedione
was reacted with each of the imines 1a–l in refluxing
anhydrous toluene for 0.5–2 h to give cycloadducts,
2,3-diaryl-6-methyl-5-phenyl-2,3-dihydro-4H-1,3-
oxazin-4-ones (2a–j), in yields of 26–57%. No cor-
responding reactions occurred with imines 2k
(R1 = Ph, R2 = p-NO2) and 2l (R1 = R2 = p-NO2)
(Scheme 1). The results indicated that the imines
reacted with acetylphenylketene specifically, al-
though 2-diazo-1-phenyl-1,3-butanedione can gen-
erate acetylphenylketene and benzoylmethylketene
in a ratio of 1.3:1 [7]. Also, it was found that the
Correspondence to: Jiaxi Xu; e-mail: jxxu@chem.pku.edu.cn.
Contract grant sponsor: NSFC.
Contract grant number: 29772002.
2002 Wiley Periodicals, Inc.
c
165

166 Xu and Chen
SCHEME 1 Reaction of ␣-diazo-␤-diketones and imines.
yields depend on the substituents; imines with
electron-donating group(s) gave higher yields and
imines with electron-withdrawing group(s) gave
lower yields, or even no reaction. For example, 2k
with one electron-withdrawing p-NO2 group and 2l
with two electron-withdrawing p-NO2 groups gave
no products. In order to verify the lack of reactivity
of imines 2k and 2l, reactions of these two imines
with the highly reactive 2-diazo-1,3-diphenyl-1,3-
propanedione was also attempted, but no desired
products were found. In additional studies, we
found that the reaction of imine 1a with 2-diazo-1,3-
diphenyl-1,3-propanedione yielded the cycloadduct
2,3-dihydro-2,3,5,6-tetraphenyl-4H-1,3-oxazin-4-
one (3). However, cyclic ␣-diazo-␤-diketone, 2-
diazo-5,5-dimethyl-1,3-cyclohexanedione, reacted
with imine 1a to give a [2 + 2] cycloadduct, a
␤-lactam derivative, 7,7-dimethyl-2,3-diphenyl-2-
azaspiro[3.4]octane-1,5-dione (4).
Furthermore, our structure was confirmed by an X-
ray crystal diffraction analysis [7,17].
Based on the above results, we can conclude
that the reaction of imines with unsymmetrical
2-diazo-1-phenyl-1,3-butanedione give generally
[2 + 4] cycloadducts derived from the imines and
acetylphenylkene, although 2-diazo-1-phenyl-1,3-
butanedione can generate both acetylphenylkene
and benzoylmethylkene.
EXPERIMENTAL
Melting points were obtained on a Yanaco melt-
ing point apparatus and are uncorrected. Elemen-
tal analyses were carried out on an Elementar Vario
1
EL elemental analyzer. The H NMR spectra were
recorded in CDCl3 solution on a Varian Mercury 200
spectrometer with TMS as an internal standard. The
IR spectra were taken on a Brucker Vector 22 FT-
IR spectrophotometer in KBr. Mass spectra were ob-
tained on a VG ZAB-HS mass spectrometer. TLC
separations were performed on silica gel G plates
with petroleum ether (30–60)/ethyl acetate (5:1) as
All cycloadducts described in the present study
1
were fully characterized by H NMR, MS, and IR
spectroscopies and by elemental analyses (Tables 1
and 2). Although product 2a was previously prepared
from imine 1a and the acylketene that was gener-
ated by pyrolysis of the appropriate 4H-1,3-dioxin-
4-one [16], the products described in [16] showed the
methyl group in the compound 2a to resonate at 1.93
ppm upfield, while that in the related compound 20a,
described [16], resonated at 1.98 ppm downfield in
1
the H NMR spectra (Scheme 2). Furthermore, the
1H NMR data of compound 2a reported in [16] did
not match with its structure. Thus, we again report
here its full characteristic data. According to our pre-
vious results [6,7] the methyl group in 6-methyl-5-
phenyl-1,3-oxazin-4-one derivatives (2) should be at
= 2.01–1.94, downfield because of the neighboring
oxygen and that in 5-methyl-6-phenyl-1,3-oxazin-4-
one derivatives (20) should be at = 1.87–1.82, up-
field because of the neighboring carbonyl group.
SCHEME 2 Reaction of unsymmetrical 2-diazo-1-phenyl-
1,3-butanedione and imines.

Reactions of Unsymmetrical ␣-Diazo-␤-Diketones with Imines 167
TABLE 1 Physical and Spectral Data
1H NMR (CDCl3/TMS)
(ppm), J (Hz)
IR
MS/FAB
Compd
2a
R 1
R 2
Yield (%) m.p. ( C)
(cm 1) C
O
(m/z) (MH +
)
Ph
H
32
44
130–131 7.60–7.19 (15H, m, aromatic),
6.70 (1H, s, CH), 1.94 (3H, s, Me)
120–121 7.50–6.80 (13H, m, aromatic),
6.56 (1H, s, CH), 3.80 (3H, s, MeO),
3.77 (3H, s, MeO), 1.96 (3H, s, Me)
1650
1660
342
402
2b
p-MeO Ph MeO
2c
2d
p-MeO Ph
H
43
26
77–78
7.50–6.90 (14H, m, aromatic),
6.65 (1H, s, CH), 3.81 (3H, s, MeO),
1.95 (3H, s, Me)
1651
1659
372
417
p-MeO Ph NO2
154–155 8.23–7.35 (13H, m, aromatic),
6.74 (1H, s, CH), 3.83 (3H, s, MeO),
1.95 (3H, s, Me)
151–152 7.54–7.17 (14H, m, aromatic),
6.66 (1H, s, CH), 1.95 (3H, s, Me)
124–125 8.31–6.25 (14H, m, aromatic),
6.76 (1H, s, CH), 1.95 (3H, s, Me)
167–168 7.60–6.82 (14H, m, aromatic),
6.61 (1H, s, CH), 3.77 (3H, s, MeO),
1.95 (3H, s, Me)
142–143 7.55–7.18 (14H, m, aromatic),
6.50 (1H, s, CH), 1.94 (3H, s, Me)
156–157 8.30–6.84 (13H, m, aromatic),
6.68 (1H, s, CH), 3.78 (3H, s, MeO),
1.96 (3H, s, Me)
2e
2f
p-ClPh
p-NO2Ph
Ph
H
38
28
57
1652
1658
1659
376
387
372
H
2g
MeO
2h
2i
Ph
Cl
43
34
1661
1649
376
417
p-NO2Ph
MeO
2j
2-Furyl
H
51
140–141 7.56–7.10 (11H, m, aromatic),
6.66 (1H, s, CH), 6.55 (1H, d,
1654
332
J = 3 Hz, CH), 6.39 (1H, d,
J = 3 Hz, CH), 1.98 (3H, s, Me)
202–203 7.62–7.18 (20H, m, aromatic),
6.70 (1H, s, CH)
215–216 7.41–7.20 (10H, m, aromatic),
5.05 (1H, s, CH), 2.58 (1H, d,
3
4
Ph
Ph
H
H
66
1659
404
320
9.4
1765
1740
J = 14 Hz, H in CH2), 2.33
(1H, d, J = 14 Hz, H in CH2),
2.11 (1H, d, J = 18 Hz, H in CH2),
1.89 (1H, d, J = 18 Hz, H in CH2),
1.22 (3H, s, Me), 1.15 (3H, s, Me)
TABLE 2 Elemental Analysis Data
Calcd.
Found
H
Compd
Molecular Formula
Molecular Weight
C
H
N
C
N
2a
2b
2c
2d
2e
2f
2g
2h
2i
C23H19NO2
341.14
401.45
371.43
416.43
375.85
386.40
371.43
375.85
416.43
331.36
403.47
319.40
80.92
74.80
77.61
69.22
73.50
71.49
77.61
73.50
69.22
76.12
83.35
78.97
5.61
5.77
5.70
4.84
4.83
4.70
5.70
4.83
4.84
5.17
5.25
6.63
4.10
3.49
3.77
6.73
3.73
7.25
3.77
3.73
6.73
4.23
3.47
4.39
81.03
75.06
77.89
69.31
73.74
71.66
77.58
73.38
69.01
76.03
83.50
79.06
5.38
5.82
5.80
5.00
4.89
4.97
5.83
5.02
5.02
5.10
5.20
6.89
3.90
3.62
3.78
6.74
3.69
7.01
4.01
3.69
6.97
4.38
3.50
4.53
C25H23NO4
C24H21NO3
C24H20N2O5
C23H18ClNO2
C23H18N2O4
C24H21NO3
C23H18ClNO2
C24H20N2O5
C21H17NO3
C28H21NO2
C21H21NO2
2j
3
4

168 Xu and Chen
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General Procedure. Imine 1 (1 mmol) and ␣-
diazo-␤-diketone (1.1 mmol) were dissolved in an-
hydrous toluene (10 ml). The resulting mixture was
refluxed for 0.5–2 h, the optimum reaction time be-
ing determined by TLC monitoring (silica gel). The
solvent was evaporated under reduced pressure to
give a residue that was crystallized from a mixture
of petroleum ether (30–60) and benzene or separated
on a silica gel column with use of petroleum ether
(30–60)/ethyl acetate (5:1) as the eluent to give color-
less crystals 2, 3, and 4.
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