Reaction of C-alkylated heterocyclic ketene aminals with diethyl azodicarboxylate: Synthesis of polyfunctionalized quaternary carbon derivatives and their thermal fragmentation

Article abstract of DOI:10.1016/S0040-4020(02)00945-6

Five-membered ring C-alkylated heterocyclic ketene aminals react with diethyl azodicarboxylate to give the quaternary carbon-containing adducts in moderate to excellent yields while the six-membered analogs afford imidazo[1,5-a]pyrimidin-6-one derivatives

Full text of DOI:10.1016/S0040-4020(02)00945-6

Tetrahedron 58 (2002) 7791–7796
Reaction of C-alkylated heterocyclic ketene aminals with diethyl
azodicarboxylate: synthesis of polyfunctionalized quaternary
carbon derivatives and their thermal fragmentation
Mei-Xin Zhao,a Zhe-Ming Wang,b Mei-Xiang Wang,a Chun-Hua Yanb and Zhi-Tang Huanga
,
*
aCenter for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, People’s Republic of China
bState Key Laboratory of Rare Earth Materials Chemistry and Application, College of Chemistry and Molecular Engineering,
Peking University, Beijing 100871, People’s Republic of China
Received 17 May 2002; revised 3 July 2002; accepted 1 August 2002
Abstract—Five-membered ring C-alkylated heterocyclic ketene aminals react with diethyl azodicarboxylate to give the quaternary carbon-
containing adducts in moderate to excellent yields while the six-membered analogs afford imidazo[1,5-a]pyrimidin-6-one derivatives. The
formation of the addition products and their fragmentation reaction pathways are discussed. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
compounds that are hardly accessible by other synthetic
methods.5
As a unique enamine analog, heterocyclic ketene aminals 1
(Fig. 1) have been shown to exhibit intriguing multi-
nucleophilic reactivity.1 For example, alkylation2 and
acylation reactions3 of aroyl-substituted heterocyclic ketene
aminals 1 (EWG¼COAr) could occur either on the
a-carbon and/or on the secondary amino nitrogen, the
selectivity depending on the reaction conditions employed.
On treatment with tetra-O-acetyl-a-D-glucopyranosyl and
-galactopyranosyl bromide in the presence of a Lewis acid
or a base, the carbonyl of the heterocyclic ketene aminals 1
was regiospecifically glycosidated.4 One of the most
noticeable features of heterocyclic ketene aminals is their
bisnucleophilicity via the a-carbon and the secondary
amino nitrogen toward bis-electrophilic reagents and this
has been successfully and frequently applied in the
preparation of a wide range of fused heterocyclic
Though the chemistry of heterocyclic ketene aminals 1 and
2 has been extensively studied, surprisingly, the reaction of
the C-alkylated analogs has remained largely unexplored.
This is most probably due to the speculation that tetra-
substituted species 3 are very stable and are as inert as 2. On
the other hand, the study of these heterocyclic ketene
aminals was probably further harnessed by the observation
of the cleavage of alkyl when treated with other electro-
philic reagents.6 Nevertheless, we envisaged that the
nucleophilic reaction of 3 at the a-carbon would generate
a polyfunctionalized quaternary carbon center. By using a
chiral auxiliary or a chiral catalyst, it would also be feasible
to develop a method to synthesize optically active
quaternary carbon compounds. As a prelude to investigating
the asymmetric synthesis of quaternary carbon compounds
utilizing heterocyclic ketene aminals protocol, we under-
took the current study.
2. Results and discussion
Our previous study demonstrated that diethyl
azodicarboxylate (DEAD) 8 is an active agent and can
react with heterocyclic ketene aminals 1 to form hydrazine
derivatives.7 To begin our study, we first chose DEAD as
probe to examine the reactivity of C-alkylated heterocyclic
ketene aminals. It was also hoped that the reaction would
lead to the formation of hydrazo- and then amino-containing
quaternary carbon products.
Figure 1. Structures of heterocyclic ketene aminals.
Keywords: C-alkylated heterocyclic ketene aminals; diethyl
azodicarboxylate; thermal fragmentation.
*
Corresponding author. Tel.: þ86-10-62544082; fax: þ86-10-62559373;
e-mail: huangzt@public.bta.net.cn
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00945-6

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M.-X. Zhao et al. / Tetrahedron 58 (2002) 7791–7796
Scheme 1.
Table 1. Reaction of heterocyclic ketene aminals 4 and 5 with DEAD 8
Entry
Reactant
Ar
R
Reaction conditions
Yield of 9 and 10 (%)a
1
2
3
4
5
6
7
8
4a
4b
4c
4d
5a
5b
5c
5d
C6H5
Ph
Ph
Ph
Ph
CHvCH2
CHvCH2
CHvCH2
CHvCH2
rt, 2 h
rt, 0.3 h
rt, 2.5 h
rt, 0.5 h
0–58C, 9 h
0–58C, 2 h
0–58C, 1 h
0–58C, 2 h
83
45
98
65
72
89
76
64
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
C6H5
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
a
Isolated yield.
The C-alkylated heterocyclic ketene aminals 4–7, which
were readily obtained from the allylation and benzylation of
tri-substituted heterocyclic ketene aminals 1, reacted rapidly
and efficiently with DEAD to afford the desired addition
products in moderate to excellent yields. For the benzyl-
substituted reactant 4, the reaction proceeded smoothly at
room temperature while for the allyl-substituted analogs 5,
the reaction took place effectively at 0–58C (Scheme 1,
Table 1). The structure of the adducts was established on the
basis of spectroscopic data and elemental analyses. Both
mass spectrum and microanalysis showed the constitution of
product being the adduct between 4 or 5 and 8 in a 1:1 ratio.
1H NMR indicated the existence of an imidazoline moiety.
Though the IR gave a characteristic carbonyl absorption
band at ,1738 cm21 corresponding to the aroyl carbonyl,
13C NMR spectra showed an ambiguous and debatable
ketonic carbon peak at ,160 ppm. The structure of 9a was
unambiguously determined by X-ray crystallography (Fig.
2).8 It should be noted that the addition products 9 and 10
appeared to be not very stable, and they are sensitive to
silica gel and acid. On exposure to air at slightly higher
temperature, they underwent decomposition in a period of
time.
In contrast to the five-membered analogs, the six-membered
heterocyclic ketene aminals 6 or 7 reacted with 8 under
similar conditions to give no desired quaternary carbon
product. Instead, imidazo[1,5-a]pyrimidin-6-one deriva-
tives 13 or 14 were obtained in moderate yield. In addition,
ethyl N-aroyl carbamate 16 was also isolated (Scheme 2).
When the reaction temperature is lowered below 258C, the
addition product was observed by thin layer chromato-
graphy. But they were found to decompose rapidly at room
temperature resulting in the formation of 13 or 14 and 16.
The structure of fused heterocycles 13 or 14 was confirmed
by the spectroscopic data and elemental analyses. The
configuration of the double bond in 13 and 14 was
determined by NOE experiments.
In order to shed further light on the reaction pathway,
thermal decomposition of adduct 9 was examined. When 9a
was refluxed in ethanol, it was decomposed to give 16a as
the sole isolable product. A mixture of compounds 12a and
16a was obtained from the heating of 9a in tetrahydrofuran
(Scheme 3). Compound 12a is the precursor of fused
heterocyclic compound 15a and it was indeed transformed
into 15a in a prolonged reaction period. Moreover, the
addition product 11c once precipitated from the reaction
between 7c and DEAD, albeit in lower purity, and its
structure was evidenced by the spectroscopic data.
To account for the results aforementioned, the mechanism
of the reaction between C-alkylated heterocyclic ketene
aminals with DEAD was proposed in Scheme 3. As
heterocyclic ketene aminals are a unique aza–ene com-
ponent,9 4–7 reacted with DEAD in most likely a conceited
aza–ene addition mechanism to produce quaternary carbon
adducts 9–11. Upon heating, intermediate 9–11 underwent
a thermal fragmentation probably via intermediate 17
followed by a decomposition to give product 16 and
Figure 2. X-Ray crystal structure of compound 9a.

M.-X. Zhao et al. / Tetrahedron 58 (2002) 7791–7796
7793
Scheme 2.
Scheme 3.
intermediate 18. Isomerization and consecutive intra-
molecular cyclocondensation of 18 led to the formation of
product 13–15.
at the a-carbon led to enhancement of the nucleophilicity of
heterocyclic ketene aminals. The five-membered C-alkyl-
ated heterocyclic ketene aminals reacted with diethyl
azodicarboxylate to give the hydrazo-containing quaternary
carbon adducts while the six-membered analogs afforded
the imidazo[1,5-a]pyrimidine derivatives. The formation of
the imidazo[1,5-a]pyrimidine derivatives has been shown to
result from the fragmentation reaction. This investigation
has provided important guidance for our future study on the
asymmetric synthesis of quaternary carbon compounds
utilizing heterocyclic ketene aminal protocols.
It is important to address that the introduction of an alkyl
group such as allyl and benzyl at the a-carbon led to the
enhancement of the nucleophilicity of the heterocyclic
ketene aminals, which is in sharp contrast to the outcome of
introducing an electron-withdrawing group. The six-
membered heterocyclic ketene aminals 6–7 appeared
more reactive than their five-membered analogs, which is
consistent with the reactivity of the parent tri-substituted
heterocyclic ketene aminals.10 The hydrazo-containing
quaternary carbon compounds obtained are not very stable
and they are ready to fragmentate to yield fused imidazo-
linone compounds and ethyl aroyl carbamate 16. The
driving force of fragmentation is probably the steric
hindrance of the bulky substituents around the quaternary
carbon and the stabilization energy gained from the
conjugation effect of the fused heterocycles formed.
Because of steric bulkiness, the six-membered adducts 11
more readily undergo fragmentation reactions than their
five-membered analogs.
4. Experimental
4.1. General
Melting points are uncorrected. IR spectra were obtained on
1
a Perkin–Elmer 782 instrument as KBr discs. H and 13C
NMR spectra were recorded in CDCl3 or d6-DMSO solution
with TMS as internal standard on a Bruker DMX-300
spectrometer. Chemical shifts are reported in ppm and
coupling constants are in Hz. Mass spectra were measured
on AEI MS-50 and KYKY-ZHP-5FAB spectrometers.
Elemental analyses were carried out at the Analytical
Laboratory of the Institute. All solvents and chemicals were
commercially available and, unless otherwise indicated,
were used as received.
3. Conclusion
The introduction of an alkyl group such as allyl and benzyl

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M.-X. Zhao et al. / Tetrahedron 58 (2002) 7791–7796
4.2. General procedure for the reaction of heterocyclic
ketene aminals (4, 5) with diethyl azodicarboxylate
(DEAD)
OCH2CH3); 13C NMR (d6-DMSO): 164.8, 163.9, 154.1,
151.5, 137.3, 134.7, 132.1, 130.1, 129.0, 128.3, 128.2,
128.0, 125.9, 61.0, 60.0, 49.6, 49.5, 14.4, 14.1; IR (KBr,
cm21): 3415 (N–H), 3169 (N–H), 1738, 1714, 1686, 1588;
MS (FAB): 487 (Mþ1)þ. Anal. calcd for C24H27ClN4O5: C,
59.19; H, 5.59; N, 11.51; found: C, 59.09; H, 5.76; N, 11.38.
To a solution of 4 or 5 (2 mmol) in tetrahydrofuran (15 mL)
was added dropwise DEAD 8 (2 mmol) in tetrahydrofuran
(5 mL) solution. The mixture was stirred (for 4, at room
temperature; for 5, at ice-bath) for several hours. After
removal of the solvent under vacuum, the residue was
recrystallized in diethyl ether to give colorless crystals 9 or
10.
4.2.5. Diethyl N-[(1-allyl-1-imidazolinyl-2-phenyl)-2-
oxo-ethyl]-hydrazine-N,N0-dicarboxylate (10a). Colorless
1
crystals; yield: 72%; mp 78–808C; H NMR (d6-DMSO):
8.60 (1H, s, NH), 8.33 (1H, s, NH), 7.87–7.45 (5H, m,
ArH), 6.52–6.45 (1H, m, vCH), 5.43–5.24 (2H, m,
vCH2), 4.17 (2H, q, J¼7.2 Hz, OCH2CH3), 3.99 (2H, q,
J¼7.2 Hz, OCH2CH3), 3.49–3.36 (6H, m, CH2þ2£NCH2),
1.25 (3H, t, J¼7.2 Hz, OCH2CH3), 1.15 (3H, t, J¼7.2 Hz,
OCH2CH3); 13C NMR (d6-DMSO): 166.3, 163.7, 154.7,
152.1, 133.8, 133.0, 132.6, 128.8, 128.7, 126.8, 121.2, 61.5,
60.7, 50.1, 49.9, 14.9, 14.6; IR (KBr, cm21): 3379 (N–H),
3184 (N–H), 1742, 1701, 1681, 1611; MS (FAB): 403
(Mþ1)þ. Anal. calcd for C20H26N4O5: C, 59.69; H, 6.51; N,
13.92; found: C, 59.77; H, 6.43; N, 13.81.
4.2.1. Diethyl N-[(1-benzyl-1-imidazolinyl-2-phenyl)-2-
oxoethyl]-hydrazine-N,N0-dicarboxylate (9a). Colorless
1
crystals; yield: 83%; mp 75–778C. H NMR (d6-DMSO):
8.40 (1H, s, NH), 7.88–7.21 (10H, m, ArH), 6.89 (1H, s,
NH), 4.21–4.09 (4H, m, 2£OCH2CH3), 3.97 (2H, s, CH2),
3.83 (2H, t, J¼9.9 Hz, NCH2), 3.59–3.53 (2H, m, NCH2),
1.26 (3H, t, J¼7.2 Hz, OCH2CH3), 1.14 (3H, t, J¼7.2 Hz,
OCH2CH3); 13C NMR (d6-DMSO): 165.7, 163.9, 154.1,
151.5, 134.8, 133.2, 132.4, 128.9, 128.3, 128.2, 127.9,
127.8, 125.9, 60.9, 60.0, 50.0, 49.6, 14.4, 14.1; IR (KBr,
cm21): 3416 (N–H), 3175 (N–H), 1739, 1711, 1682; MS
(FAB): 453 (Mþ1)þ. Anal. calcd for C24H28N4O5: C, 63.70;
H, 6.24; N, 12.38; found: C, 63.79; H, 6.44; N, 12.17.
4.2.6. Diethyl N-[(1-allyl-1-imidazolinyl-2-p-methyl-
phenyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxylate
(10b). Colorless crystals; yield: 89%; mp 92–948C. 1H
NMR (d6-DMSO): 8.66 (1H, s, NH), 8.39 (1H, s, NH), 7.79
(2H, d, J¼7.8 Hz, ArH), 7.29 (2H, d, J¼7.8 Hz, ArH),
6.54–6.47 (1H, m, vCH), 5.45–5.28 (2H, m, vCH2), 4.17
(2H, q, J¼7.2 Hz, OCH2CH3), 4.01 (2H, q, J¼7.2 Hz,
OCH2CH3), 3.62–3.38 (6H, m, CH2þ2£NCH2), 2.37 (3H,
s, CH3), 1.26 (3H, t, J¼7.2 Hz, OCH2CH3), 1.17 (3H, t,
J¼7.2 Hz, OCH2CH3); 13C NMR (d6-DMSO): 165.8, 163.5,
154.6, 152.0, 143.1, 132.5, 130.8, 129.2, 128.7, 126.7,
121.0, 61.3, 60.7, 50.0, 48.8, 21.3, 14.8, 14.5; IR (KBr,
cm21): 3384 (N–H), 3102 (N–H), 1740, 1702, 1684, 1606;
MS (FAB): 417 (Mþ1)þ. Anal. calcd for C21H28N4O5: C,
60.56; H, 6.78; N, 13.45; found: C, 60.51; H, 6.86; N, 13.45.
4.2.2. Diethyl N-[(1-benzyl-1-imidazolinyl-2-p-methyl-
phenyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxylate (9b).
Colorless crystals; yield: 45%; mp 90–928C; 1H NMR (d6-
DMSO): 10.82 (1H, s, NH), 7.78–7.20 (9H, m, ArH), 6.75
(1H, s, NH), 4.19–4.08 (4H, m, 2£OCH2CH3), 3.95 (2H, s,
CH2), 3.82 (2H, t, J¼9.9 Hz, NCH2), 3.34–3.30 (2H, m,
NCH2), 2.34 (3H, s, CH3), 1.24 (3H, t, J¼7.2 Hz, OCH2
CH3), 1.14 (3H, t, J¼7.2 Hz, OCH2CH3); 13C NMR (d6-
DMSO): 165.8, 164.3, 154.4, 151.9, 143.1, 135.1, 130.7,
129.3, 129.2, 128.9, 128.6, 128.3, 126.3, 61.2, 60.3, 50.2,
50.0, 21.3, 14.7, 14.5; IR (KBr, cm21): 3406 (N–H), 3171
(N–H), 1738, 1704, 1679, 1603; MS (FAB): 467 (Mþ1)þ.
Anal. calcd. for C25H30N4O5: C, 64.36; H, 6.48; N, 12.01;
found: C, 64.18; H, 6.46; N, 11.79.
4.2.7. Diethyl N-[(1-allyl-1-imidazolinyl-2-p-methoxy-
phenyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxylate
(10c). Colorless crystals; yield: 76%; mp 97–998C; 1H
NMR (d6-DMSO): 8.61 (1H, s, NH), 8.32 (1H, s, NH), 7.86
(2H, d, J¼8.7 Hz, ArH), 6.99 (2H, d, J¼8.7 Hz, ArH),
6.50–6.44 (1H, m, vCH), 5.41–5.24 (2H, m, vCH2), 4.14
(2H, q, J¼7.2 Hz, OCH2CH3), 3.98 (2H, q, J¼7.2 Hz,
OCH2CH3), 3.80 (3H, s, OCH3), 3.46–3.35 (6H, m,
CH2þ2£NCH2), 1.23 (3H, t, J¼7.2 Hz, OCH2CH3), 1.14
(3H, t, J¼7.2 Hz, OCH2CH3); 13C NMR (d6-DMSO): 165.3,
163.6, 163.1, 154.7, 152.2, 132.5, 130.9, 126.9, 125.7,
121.2, 114.1, 61.3, 60.8, 55.9, 49.7, 49.5, 14.9, 14.7; IR
(KBr, cm21): 3345 (N–H), 3150 (N–H), 1715, 1679, 1655,
1578; MS (FAB): 433 (Mþ1)þ. Anal. calcd for
C21H28N4O6: C, 58.32; H, 6.53; N, 12.96; found: C,
58.31; H, 6.62; N, 13.07.
4.2.3. Diethyl N-[(1-benzyl-1-imidazolinyl-2-p-methoxy-
phenyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxylate (9c).
Colorless crystals; yield: 98%; mp 79–818C; 1H NMR
(d6-DMSO): 10.78 (1H, s, NH), 7.90–6.90 (9H, m, ArH),
6.76 (1H, s, NH), 4.20–4.10 (4H, m, 2£OCH2CH3), 3.97
(2H, s, CH2), 3.91–3.83 (7H, m, 2£NCH2þOCH3), 1.26
(3H, t, J¼6.9 Hz, OCH2CH3), 1.17 (3H, t, J¼6.9 Hz,
OCH2CH3); 13C NMR (d6-DMSO): 164.8, 164.0, 162.6,
154.1, 151.6, 134.8, 130.4, 128.9, 128.0, 127.9, 125.9,
125.2, 113.5, 60.8, 60.0, 55.4, 50.0, 49.8, 14.4, 14.1; IR
(KBr, cm21): 3401 (N–H), 3178 (N–H), 1737, 1717, 1673,
1599; MS (FAB): 483 (Mþ1)þ. Anal. calcd for
C25H30N4O6: C, 62.23; H, 6.27; N, 11.61; found: C,
61.80; H, 6.57; N, 11.37.
4.2.8. Diethyl N-[(1-allyl-1-imidazolinyl-2-p-chloro-phe-
nyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxylate
(10d).
4.2.4. Diethyl N-[(1-benzyl-1-imidazolinyl-2-p-chloro-
phenyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxylate (9d).
Colorless crystals; yield: 65%; mp 76–788C; 1H NMR (d6-
DMSO): 8.49 (1H, s, NH), 7.90–7.28 (9H, m, ArH), 6.90
(1H, s, NH), 4.18 (2H, q, J¼6.9 Hz, OCH2CH3), 3.93 (2H,
q, OCH2CH3), 3.39–3.35 (6H, m, 2£NCH2þCH2), 1.26
(3H, t, J¼6.9 Hz, OCH2CH3), 1.09 (3H, t, J¼7.2 Hz,
Colorless crystals; yield: 64%; mp 92–948C; 1H NMR
(d6-DMSO): 8.65 (1H, s, NH), 8.33 (1H, br., NH), 7.83 (2H,
d, J¼8.4 Hz, ArH), 7.51 (2H, d, J¼8.4 Hz, ArH), 6.48–6.41
(1H, m, vCH), 5.38–5.22 (2H, m, vCH2), 4.12 (2H, q,
J¼7.2 Hz, OCH2CH3), 3.98 (2H, q, J¼7.2 Hz, OCH2CH3),
3.40–3.30 (6H, m, CH2þ2£NCH2), 1.21 (3H, t, J¼6.9 Hz,

M.-X. Zhao et al. / Tetrahedron 58 (2002) 7791–7796
7795
OCH2CH3), 1.12 (3H, t, J¼6.9 Hz, OCH2CH3); 13C NMR
(d6-DMSO): 165.4, 163.7, 154.7, 152.1, 137.8, 132.6, 130.7,
128.9, 128.8, 126.9, 121.3, 61.5, 60.7, 49.9, 49.7, 14.9, 14.6;
IR (KBr, cm21): 3382 (N–H), 3184 (N–H), 1739, 1699,
1686, 1609; MS (FAB): 437 (Mþ1)þ. Anal. calcd for
C20H25ClN4O5: C, 54.98; H, 5.77; N, 12.82; found: C,
55.20; H, 5.86; N, 12.65.
pressure. The residue was chromatographed on a silica gel
column to give the decomposed product 14.
4.4.2. 8-Allylidene-3,4,7,8-tetrahydro-2H-imidazo[1,5-
a]pyrimidin-6-one (14). Colorless crystals; yield: 59%;
mp 119–1218C; 1H NMR (CDCl3): 9.55 (1H, s, NH), 6.58–
6.45 (1H, m, vCH), 6.15 (1H, d, J¼11.7 Hz, vCH), 5.37
(1H, d, J¼16.5 Hz, vCH), 5.24 (1H, d, J¼10.2 Hz, vCH),
4.3. Reaction of heterocyclic ketene aminals (6a) with
DEAD (8)
3.65–3.56 (4H, m, 2£NCH2), 1.89–1.81 (2H, m, CH2); 13
C
NMR (CDCl3): 155.3, 148.3, 129.5, 129.0, 120.0, 105.3,
44.5, 37.2, 19.3; IR (KBr, cm21): 3195 (NH), 1744, 1728,
1649, 1429; MS (EI): 177 (Mþ, 28%), 176 (M21, 100), 148
(50). Anal. calcd for C9H11N3O: C, 61.00; H, 6.26; N:
23.71; found: C, 60.82; H, 6.38; N, 23.80.
To a solution of 6a (2 mmol) in tetrahydrofuran (15 mL)
was added dropwise DEAD 8 (2 mmol) in tetrahydrofuran
(5 mL). The mixture was stirred at room temperature for
2 h. After removal of solvent under vacuum, the residue was
chromatographed on a silica gel column (ether acetate/
petroleum ether as an eluant) to give products 13 and 16a.
4.5. Thermal fragmentation of adducts (9a)
A solution of adducts 9a (1 mmol) in tetrahydrofuran
(15 mL) was refluxed for about 5 h (monitored by TLC).
Removal of the solvent and chromatographed by silica gel
column (ethyl acetate/petroleum ether as eluant) to afford
the product 12a and 16a. 12a and 16a can also be obtained
by refluxing the mixture of heterocyclic ketene aminal 4a
and DEAD 8 in tetrahydrofuran in a one-pot reaction.
4.3.1. 8-Benzylidene-3,4,7,8-tetrahydro-2H-imidazo[1,5-
a]pyrimidin-6-one (13). Colorless crystals; yield: 63%; mp
177–1798C; H NMR (CDCl3): 7.66 (1H, s, NH), 7.42–
7.30 (5H, m, ArH), 6.54 (1H, s, vCH), 3.66 (4H, t,
J¼5.7 Hz, 2£NCH2), 1.91 (2H, q, J¼5.7 Hz, CH2); 13C
NMR (CDCl3): 154.9, 148.4, 134.2, 128.7, 128.3, 128.0,
127.3, 104.0, 44.7, 37.2, 19.4; IR (KBr, cm21): 3448 (NH),
1740, 1738, 1649; MS (EI): 227 (Mþ, 21%), 226 (M21,
100), 198 (28). Anal. calcd for C13H13N3O: C, 68.70; H,
5.76; N, 18.49; found: C, 68.56; H, 5.75; N, 18.52.
1
4.5.1. Ethyl N-(1-imidazolinyl-2-phenyl-vinyl)carbamate
1
(12a). Colorless crystals; yield: 65%; mp 134–1368C; H
NMR (CDCl3): 7.73 (1H, s, NH), 7.46–7.23 (5H, m, ArH),
6.99 (1H, s, NH), 6.75 (1H, s, vCH), 4.08 (2H, q,
J¼6.9 Hz, OCH2CH3), 3.68 (4H, s, 2£NCH2), 1.17 (3H, m,
OCH2CH3); 13C NMR (CDCl3): 164.3, 154.1, 134.7, 129.0,
128.4, 128.3, 124.9, 124.8, 61.7, 50.4, 14.4; IR (KBr, cm21):
3308 (NH), 1781, 1586, 1535; MS (EI): 259 (Mþ, 3%), 258
(M21, 16), 212 (100). Anal. calcd for C14H17N3O2: C, 64.84;
H, 6.61; N, 16.21; found: C, 64.47; H, 6.58; N, 16.08.
4.3.2. Ethyl N-benzoyl carbamate (16a). White solid;
yield: 70%; mp 90–928C; 1H NMR (d6-DMSO): 10.97 (1H,
s, NH), 7.89–7.47 (5H, m, ArH), 4.18 (2H, q, J¼7.2 Hz,
OCH2CH3), 1.26 (3H, t, J¼7.5 Hz, OCH2CH3). 13C NMR
(CDCl3): 165.6, 151.7, 133.3, 129.1, 129.1, 128.1, 62.6,
14.6. IR (KBr, cm21): 3260, 1758, 1740; MS (EI): 193 (Mþ,
8%), 149 (10), 105 (100). Anal. calcd for: C10H11NO3: C,
62.16; H, 5.74; N, 7.25; found: C, 62.09; H, 5.77; N, 7.19.
Prolonging the reaction time lead to the formation of
imidazo[1,5-a]imidazolinone 15a.
4.4. Reaction of heterocyclic ketene aminals (7c) with
DEAD (8)
4.5.2. 7-Benzylidene-2,3,6,7-tetrahydroimidazo[1,5-
a]imidazol-5-one (15a). White solid; yield: 66%; mp
197–1998C; 1H NMR (d6-DMSO): 10.08 (1H, s, NH),
7.54–7.23 (5H, m, ArH), 6.31 (1H, s, vCH), 4.26 (2H, t,
J¼8.7 Hz, NCH2), 3.64 (2H, t, J¼8.7 Hz, NCH2); 13C NMR
(d6-DMSO): 160.7, 152.6, 133.9, 128.9, 127.8, 125.1, 125.0,
105.1, 61.6, 41.5; IR (KBr, cm21): 3227 (NH), 1748, 1645,
1407; MS (EI): 213 (Mþ, 31%), 212 (M21, 100), 117 (59).
Anal. calcd for C12H11N3O: C, 67.59; H, 5.20; N, 19.71;
found: C, 67.16; H, 5.09; N, 19.68.
To a solution of heterocyclic ketene aminals 7c (2 mmol) in
tetrahydrofuran (15 mL) was added dropwise diethyl
azodicarboxylate 8 (2 mmol) at room temperature. After
0.5 h, white solid participated from the mixture, collected
the solid by filtration and dried to give the crude adduct 11c.
4.4.1. Diethyl N-[(1-allyl-1-tetrahydropyrimidinyl-2-p-
methoxyphenyl)-2-oxoethyl]-hydrazine-N,N0-dicarboxyl-
1
ate (11c). White solid. H NMR (d6-DMSO): 9.54 (1H, s,
NH), 8.55 (1H, s, NH), 7.89 (2H, d, J¼8.4 Hz, ArH), 7.00
(2H, d, J¼8.4 Hz, ArH), 5.57–5.49 (1H, m, vCH), 5.19–
5.12 (2H, m, vCH2), 4.30–4.21 (2H, m, OCH2CH3), 3.93–
3.85 (5H, m, OCH2CH3þOCH3), 3.45–3.35 (6H, m,
CH2þ2£NCH2), 1.91–1.84 (2H, m, CH2), 1.28 (3H, t,
J¼6.6 Hz, OCH2CH3), 0.87 (3H, t, J¼6.6 Hz, OCH2CH3);
IR (KBr, cm21): 3350 (N–H), 3128 (N–H), 1742, 1694,
1645, 1598; MS (FAB): 447 (Mþ1)þ.
Acknowledgements
The financial support from the Major Basic Research
Development Program (no. G2000077502), the National
Natural Science Foundation of China and the Chinese
Academy of Sciences is gratefully acknowledged.
A solution of 11c (1 mmol) in tetrahydrofuran (10 mL) was
stirred at room temperature for another 4 h and the process
was monitored by thin layer chromatography. After the
substrate disappeared, the solvent was removed by reduced
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