Facile synthesis of oxaspirobicyclic butenolides via a domino Michael addition/aldol reaction/γ-lactonization sequence

Article abstract of DOI:10.1016/j.tet.2010.03.058

A three-component domino reaction approach between a primary amine, a dialkyl acetylenedicarboxylate, and 1,3-dimethylalloxan that affords novel oxaspirobicyclic γ-butenolidobarbiturate derivatives is reported. The reaction sequence consists of an initial Michael-addition of primary amines to dialkyl acetylenedicarboxylates, followed by aldol-like reaction with 1,3-dimethylalloxan, and then γ-lactonization to afford the products. This cascade reaction sequence represents a rapid and unprecedented route to the described biologically interesting molecules.

Full text of DOI:10.1016/j.tet.2010.03.058

Tetrahedron 66 (2010) 3795–3800
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Facile synthesis of oxaspirobicyclic butenolides via a domino Michael
addition/aldol reaction/
g
-lactonization sequence
,
b
Mohammad Bagher Teimouri a , Tayyebeh Abbasi
*
a Petrochemical Department, Iran Polymer and Petrochemical Institute, PO Box 14965-115, Tehran 1497713115, Iran
b Department of Chemistry, University of Zanjan, PO Box 45195-313, Zanjan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 January 2010
Received in revised form 24 February 2010
Accepted 15 March 2010
Available online 20 March 2010
A three-component domino reaction approach between a primary amine, a dialkyl acetylenedicarbox-
ylate, and 1,3-dimethylalloxan that affords novel oxaspirobicyclic
reported. The reaction sequence consists of an initial Michael-addition of primary amines to dialkyl
acetylenedicarboxylates, followed by aldol-like reaction with 1,3-dimethylalloxan, and then -lactoni-
g-butenolidobarbiturate derivatives is
g
zation to afford the products. This cascade reaction sequence represents a rapid and unprecedented route
to the described biologically interesting molecules.
Keywords:
Amine
Ó 2010 Elsevier Ltd. All rights reserved.
Acetylenic ester
Alloxan
Barbiturate
g-Butenolides
Multicomponent reaction
1. Introduction
some flowers.6 This includes (þ)-leptosphaerin7 and compound
WF-3681,8 distomadine B,9 various ascorbic acid (vitamin C) de-
Drugs belonging to the class of barbiturates have been used for
more than a century as hypnotics and anticonvulsants.1 Pharma-
ceutical industries market more than 50 barbiturate derivatives
under various trade names,2 and few people have not heard of the
name of phenobarbital as the most widely used anticonvulsant
worldwide and the earliest still in use. On the other hand,
rivatives,10 and many other pharmacologically relevant natural
products.11 Isotetronic acids have been used also as synthetic
building blocks during the synthesis of (ꢀ)-tetrodotoxin,12 6-thio-
sialic, and neuraminic acids,13–16 nactins,17 and erythronolide A.18
The butenolide structural unit is usually constructed by one of
the following strategies:4,19 (1) reaction of metal carbonyl com-
plexes with alkynes;20 (2) lactonization of 3-hydroxy-1-alkenyl
carboxylic acids;21 (3) selective partial reduction of cyclic anhy-
drides;22 (4) regioselective oxidation of substituted furans;23 (5)
Pd-catalyzed carbonylative lactonization of 3-iodo-2(Z)-prope-
nol;24 (6) Pd-catalyzed carbonylative cyclization of 2-alkynols;25
(7) radical cyclization of 20-bromoalkyl 2-alkynoates;26 (8) lacto-
nization of 2,3-allenoates using a variety of electrophiles;27 (9)
cyclization of allenic acid precursors catalyzed by transition metal,
such as Ag(I)28a and Au(III);28b (10) ring closing metathesis;29 (11)
phosphine-mediated reactions of ketones with methyl acetox-
ypropynoate30 or acetylenic esters;31 (12) cyclizations of oxalyl
chloride with acetophenone derived silyl enol ethers32 or 1,3-
dicarbonyl compounds33 1,3-bis(silyloxy)alk-1-enes.34
a,b-unsaturated g-butyrolactones, also named, g-butenolides, are
important targets in organic synthesis, as these structures are
found in a large variety of biologically active natural products.3
g-Butenolides with different substitution patterns are considered
as potential insecticides, bactericides, antibiotics, anticancer
agents, antiinflammatories, allergy inhibitors, antipsoriasis agents,
cyclooxygenase inhibitors, phospholipase A2 inhibitors, etc.4
Moreover, 4-alkoxycarbonyl-butenolides are also important syn-
thetic building blocks. For example, (þ)-nephrosteranic acid and
related
g-lactones were prepared by diastereoselective hydroge-
nation of 5-alkyl-3-mesyloxy-4-ethoxycarbonyl-butenolides.5 Iso-
tetronic acid derivatives, containing a hydroxy group at carbon
atom C-3 of the butenolide moiety, are also occurring in many
natural products. It has been reported that 3-hydroxy-
g-butenolide
Although, there are many ways to synthesize the g-butenolide
and 3-amino- -butenolide scaffolds are responsible for the odor of
g
moiety, to the best of our knowledge up to now only two one-pot
multicomponent approaches31,35 have been published. The con-
struction of multiple carbon–carbon and carbon–heteroatom
bonds by tandem reactions represents an efficient approach to the
synthesis of complex molecular structures from simple organic
* Corresponding author. Tel.: þ98 21 44580000; fax: þ98 21 44580032; e-mail
address: m.teimouri@ippi.ac.ir (M.B. Teimouri).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.058

3796
M.B. Teimouri, T. Abbasi / Tetrahedron 66 (2010) 3795–3800
building blocks.36,37 The variation and structural diversity of the
target molecules in question had a strong impact on the de-
velopment of synthetic methods.
88–96% yields; the full results are summarized in Table 1. 1H and 13
NMR spectra of the crude products clearly indicated the formation
of oxaspirobicyclic -butenolides 4. No other product was detected
C
g
In connection with our recent research on alloxans,38 guided by
observation that the presence of two or more different heterocyclic
moieties in a single molecule often enhances the biological profile
by NMR spectroscopy.
The structures of the products 4a–k were deduced from their
elemental analyses and IR, 1H NMR and 13C NMR spectra. For ex-
ample, the 1H NMR spectrum of 4a exhibited two single sharp lines
readily recognized as arising from two equivalent N–CH3 groups (dH
3.31 ppm) and methoxy protons along with three fairly broad sin-
glets for the methylenes (dH 1.65 and 2.06 ppm) and methines (dH
2.09 ppm) of adamantyl moiety. A broad singlet (dH 7.07 ppm) was
observed for the NH group. The presence of an amine proton was
confirmed by exchange with D2O. The chemical shift of the NH
group indicates that this moiety must have participated in a six-
membered intramolecular hydrogen bond formation with the vic-
inal carbonyl group.
remarkably, we investigated
a three-component reaction of
primary amines, dialkyl acetylenedicarboxylates, and 1,3-dime-
thylalloxan in dry CH2Cl2, which afforded oxaspirobicyclic
g-butenolides containing barbiturate moiety in high isolated yields.
2. Results and discussion
We examined the reaction of the primary amines with dialkyl
acetylenedicarboxylate in the presence of alloxan derivatives in dry
CH2Cl2 at room temperature (25 ꢁC) and we obtained the corre-
sponding alkyl 3-(alkyl or arylamino)-7,9-dimethyl-2,6,8,10-
The 1H decoupled 13C NMR spectrum of 4a showed 13 distinct
signals, which confirmed the proposed structure. The characteristic
tetraoxo-1-oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylates
4 in
Table 1
Three-component condensation reactions of primary amines, dialkyl acetylenedicarboxylates, and 1,3-dimethylalloxan in dry dichloromethane
O
O
CO2R'
Me
Me
O
O
O
O
N
N
CH2Cl2
rt, 3 h
R
NH2
O
+
+
N
N
Me
Me
NHR
O
R'O2C
CO2R'
O
1
2
4
3
Entry
R
R0
Product
Yielda (%)
O
Me
O
O
O
N
O
1
Me
Me
96
N
N
Me
H
MeO2C
4a
O
Me
O
O
O
N
O
2
92
N
N
Me
H
MeO2C
4b
O
Me
O
O
O
N
Me
O
Me
Me
3
4
Me
Me
95
88
N
N
Me
Me
Me
H
MeO2C
4c
O
O
O
O
Me
N
Me
O
Me
N
Me
Me
N
Me
Me
H
MeO2C
4d
O
Me
O
O
O
N
N
O
5
6
Me
Me
88
90
Me
N
Me
Me
H
O
MeO2C
4e
Me
O
O
N
O
Me
N
N
Me
O
Me
H
MeO2C
4f

M.B. Teimouri, T. Abbasi / Tetrahedron 66 (2010) 3795–3800
3797
Table 1 (continued)
Entry
R
R0
Product
Yielda (%)
O
Me
N
O
O
O
O
7
Et
91
89
90
N
N
Me
H
EtO2C
4g
4h
O
Me
O
O
O
N
N
O
8
Et
Et
N
Me
H
EtO2C
O
Me
O
O
O
N
O
9
N
N
Me
H
EtO2C
4i
O
Me
O
O
O
N
Me
O
Me
Me
10
Et
Et
91
93
N
N
Me
Me
H
EtO2C
4j
O
Me
O
O
O
N
O
11
N
Me
N
Me
Me
H
EtO2C
4k
a
Refers to purified yield, which is >95% as determined by 1H NMR.
signal due to the spiro carbon was discernible at dC 106.1 ppm and
four carbonyl groups were resonated at dC 150.3, 163.2, 164.8, and
164.9 ppm. Partial assignment of these resonances is given in
Experimental section.
nucleophilic Michael-addition of the primary amine 1 to the
-carbon of the electron-deficient alkyne 2 generates the amino-
b
butendioate 5 as an electron-rich enaminone.39 The central car-
bonyl groups of the vicinal tri-carbonyl compounds, such as alloxan
derivatives possess outstanding electrophilic (electron-pair-
accepting) properties.40 The polar reactions with carbanion-like
(electron rich) species, such as enaminones give rise to nucleo-
philic addition reactions of carbonyl groups under exclusive C–C
bond formation.41 Subsequent nucleophilic aldol-like attack of
aminobutendioate 5 to the central carbonyl group of the 1,3-
dimethylalloxan 3 would yield iminium–oxyanion intermediate 6,
The structural assignments made on the basis of the 1H and 13
C
NMR spectra of compounds 4a was supported by measurement of
its IR spectra. The IR spectrum of 4a showed strong absorptions at
1798, 1695, and 1628 cmꢀ1 due to the carbonyls and the amino
group at 3314 cmꢀ1 as a weak band.
The scope and limitations of this three-component reaction
were explored by using two dialkyl acetylenedicarboxylates and
a wide range of primary amines. A variety of structurally diverse
amines underwent the one-pot reaction smoothly without using
that can be tautomerized to hydroxy barbiturates 7.
g-Lactonization
of Z-7 (compound 7 with the Z-configuration around the C]C
any catalyst to afford the corresponding spirocyclic
g-butenolide
double bond), would produce the oxaspirobicyclic g-butenolido-
derivatives in high yields. As shown in Table 1, the allylic, benzylic,
hindered, and unhindered primary amines are used in this protocol
with excellent results. Thus, a diverse set of biologically useful
barbiturates 4.
As shown in Scheme 1, at least three distinct reactions (Michael
addition, stereocontrolled aldol-type reaction and lactonization)
occur in this one-pot process. All these steps take place in an or-
dered manner to provide the final compound with concomitant
creation of three chemical bonds. Two irreversible steps (the for-
mation of eneminone and lactonization) cause the observed re-
action sequence to be a unique and a productive process.
In solution, 2-aminobutenedioates can exist in (Z)- and/or
(E)-isomeric forms with respect to C]C double bond. In most cases,
the substituent at C-2 (e.g., the alkyl or arylamino group) was found
to be oriented trans with respect to the ester group or analogous
structural element at C-4. So far, only a few examples of 2-amino-
butenedioates with the opposite configuration around the C]C
double bond, where the substituent at C-2 and the ester group are
cis oriented, have been found.42
g-butenolide products can be potentially prepared in one step by
this method. However, the secondary amines, such as diethyl
amine, morpholine, and thiomorpholine have not participated in
the reaction. We also tried to take advantage of 25% aqueous am-
monia, 50% aqueous hydroxylamine and phenylhydrazine as the
amine component. Unfortunately, the reaction of 1,3-dimethy-
lalloxan and dimethyl acetylenedicarboxylates with each of these
NH2-containing compounds did not afford the desired barbiturate
under the same reaction conditions.
A possible mechanism for the present reaction is shown in
Scheme 1, which envisages a tandem sequence. On the basis of the
well established chemistry of trivalent nitrogen nucleophiles, the
successful nucleophilic attack by amines on a carbon atom is fa-
cilitated when the latter is conjugated with a carbonyl group, or
when it is a part of an unsaturated bond otherwise activated. First,
The configuration of the 2-aminobutenedioate moiety con-
cerning the orientation around the C]C bond is the most

3798
M.B. Teimouri, T. Abbasi / Tetrahedron 66 (2010) 3795–3800
Me
O
O
N
N
Me
O
O
O
O
CO2R'
CO2R'
N
N
..
CO2R'
O
H
RNH
CO2R'
H
Me
..
NH2
R
+
O
Me
R'O2C
R'O2C
N
R
5
H
6
iminium-enamine
tautomerization
Me
O
OH O
N
O
Me
Me
O
O
O
OR'
O
N
N
N
O
O
Me
- R'OH
NHR
R'O2C
N R
R'O2C
H
7
4
(Z)-isomer
Scheme 1. Multicomponent synthesis of barbiturate-containing oxaspirobicyclic butenolides 4; a possible reaction sequence.
significant key factor that dictates the outcome of a given
nization. In the (E) configuration, the ester group is opposite to
hydroxy group and this arrangement is not suitable for -lactoni-
zation because a trans C]C bond-containing a five-membered ring
cannot be formed, energetically. While, the Z-configuration of 7 in
g
-lacto-
using residual undeuterated solvent as an internal reference.
Chemical shifts are reported in parts per million (ppm) relative to
TMS as internal reference. Analytical TLC was carried out on pre-
coated plates (Merck silica gel 60, F254) and visualized with UV
light. All chemical reagents were obtained from Merck, Fluka or
Acros and were used without further purification.
g
the formation of spiro g-butenolide 4 is highly desirable.
Some pieces of evidence are available to contribute toward
a discussion of the mechanism of the tandem reaction. The key step
in the synthesis is an efficient component reaction of a primary
amine with a dialkyl acetylenedicarboxylate to give a 2-alkylamino-
2-butendioate derivative, which then reacts with alloxan de-
rivatives. In order to confirm the route mechanism of the reaction
in Scheme 1, via the formation of 2-alkylamino-2-butendioate
intermediate in the first stage of the reaction, diethyl 2-(iso-
butylamino)-2-butendioate 7j as a representative of 2-alkylamino-
2-butendioate was synthesized separately by the condensation of
isobutylamine and diethyl acetylenedicarboxylate. Then, we ex-
amined the reaction of the isolated diethyl 2-(isobutylamino)-2-
butendioate with one equivalent amount of 1,3-dimethylalloxan in
water, and we obtained the product 4j with 93% yield.
4.2. Typical procedure for preparation of methyl 3-(1-
adamantylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-oxa-7,9-
diazaspiro[4.5]dec-3-ene-4-carboxylate (4a)
To a magnetically stirred solution of 1-adamantylamine (0.151 g,
1.0 mmol) and dimethyl acetylenedicarboxylate (0.143 g, 1.0 mmol)
in dry CH2Cl2 (10 mL) was added 1,3-dimethylalloxan (0.170 g,
1.0 mmol) at room temperature (25 ꢁC). The reaction mixture was
then stirred for 3 h. The solvent was removed under reduced
pressure and the residue was treated with diethylether (5 mL) to
give 4a as a white powder (0.414 g, 96%). The dried product thus
obtained showed a single spot on TLC and was pure enough for all
analytical purposes. Mp 200–202 ꢁC; IR (KBr) (nmax, cmꢀ1): 3314
(N–H), 1798, 1695, 1628, (C]O); 1H NMR (400.1 MHz, CDCl3): dH
1.65 and 2.06 (12H, 2br s, 6CH2 of adamantyl), 2.09 (3H, br s, 3CH of
adamantly), 3.31 (6H, s, 2NCH3), 3.64 (3H, s, OCH3), 7.07 (1H, br s,
NH); 13C NMR (100.7 MHz, CDCl3): dC 164.9, 164.8, 163.2, 150.3,
143.9, 106.1, 77.9, 54.9, 52.0, 42.7, 35.6, 29.7, 29.4. Anal. Calcd for
C21H25N3O7 (431.44): C, 58.46; H, 5.84; N, 9.74%. Found: C, 58.29; H,
5.80; N, 9.82%.
3. Conclusion
The present work describes a tandem protocol for the synthesis
of new alkyl 3-(alkyl or arylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-
1-oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylates via a Michael
addition, stereocontrolled aldol-type reaction, and
g-lactonization
sequence. A library of novel oxaspirobicyclic -butenolidobarbitu-
g
rates bearing two biologically interesting sub-structures can be
rapidly accessed using this methodology. The one-pot multicom-
ponent protocol has several distinct advantages over sequential
multi-step procedures. These include superior atom economy,
simplified workup procedures, greater efficiency, and superior
overall yields.
4.2.1. Methyl
3-(benzylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-
oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4b). White pow-
der (0.356 g, 92%); mp 136–138 ꢁC; IR (KBr) (nmax, cmꢀ1): 3355 (N–
H), 1790, 1690, 1640 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 3.28
(6H, s, 2NCH3), 3.59 (3H, s, OCH3), 4.92 (2H, d, 3JHH¼4.8 Hz, NHCH2),
6.93 (1H, br s, NH), 7.26–7.30 (5H, m, C6H5); 13C NMR (100.7 MHz,
CDCl3): dC 165.6, 164.6, 162.8, 150.2, 141.6, 137.6, 128.9, 127.9, 127.5,
105.6, 65.8, 52.1, 46.2, 29.4. Anal. Calcd for C18H17N3O7 (387.34): C,
55.81; H, 4.42; N, 10.85%. Found: C, 55.97; H, 4.47; N, 10.72%.
4. Experimental
4.1. General
4.2.2. Methyl 3-(isobutylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-
oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4c). White powder
(0.336 g, 95%); mp 112–114 ꢁC; IR (KBr) (nmax, cmꢀ1): 3365 (N–H),
1792, 1762, 1692, 1636 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 0.92
Melting points were measured on a Bu¨chi 535 apparatus and are
uncorrected. Elemental analyses were performed using an ele-
mentar vario EL III instrument. FT-IR Spectra were recorded on
a Bruker Equinox-55 spectrometer. 1H and 13C NMR spectra were
recorded on a Bruker DRX-400 Avance spectrometer at 400.13 and
100.77 MHz, respectively, with CDCl3 as solvents and calibrated
3
(6H, d, JHH¼6.6 Hz, CH(CH3)2), 1.80 (1H, m, CH(CH3)2), 3.31 (6H, s,
2NCH3), 3.57 (2H, m, NHCH2CH), 3.65 (3H, s, OCH3), 6.90 (1H, br s,
NH); 13C NMR (100.7 MHz, CDCl3): dC 165.3, 164.7, 163.0, 150.2,

M.B. Teimouri, T. Abbasi / Tetrahedron 66 (2010) 3795–3800
3799
142.7, 104.6, 76.8, 52.0, 49.4, 29.8, 29.4, 19.6. Anal. Calcd for
C15H19N3O7 (353.32): C, 50.99; H, 5.42; N,11.89%. Found: C, 51.14; H,
5.34; N, 11.95%.
7.34 (5H, m, C6H5); 13C NMR (100.7 MHz, CDCl3): dC 165.6, 164.7,
162.5, 150.2, 142.2, 137.4, 129.0, 128.0, 127.6, 105.8, 77.3, 61.0, 46.3,
29.4, 14.0. Anal. Calcd for C19H19N3O7 (401.37): C, 56.86; H, 4.77; N,
10.47%. Found: C, 56.73; H, 4.81; N, 10.52%.
4.2.3. Methyl 3-(tert-butylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-
oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4d). White pow-
der (0.310 g, 88%); mp 157–159 ꢁC; IR (KBr) (nmax, cmꢀ1): 3318 (N–
H), 1799, 1694, 1627 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 1.48
(9H, s, C(CH3)3), 3.33 (6H, s, 2NCH3), 3.66 (3H, s, OCH3), 7.24 (1H, br
s, NH); 13C NMR (100.7 MHz, CDCl3): dC 164.7, 163.2, 150.2, 143.8,
106.1, 77.8, 54.4, 51.9, 30.5, 29.4. Anal. Calcd for C15H19N3O7
(353.32): C, 50.99; H, 5.42; N, 11.89%. Found: C, 51.48; H, 5.45; N,
11.78%.
4.2.9. Ethyl 3-(isobutylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-oxa-
7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4j). White powder
(0.334 g, 91%); mp 174–176 ꢁC; IR (KBr) (nmax, cmꢀ1): 3341 (N–H),
1799, 1703, 1668, 1638 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 0.96
3
3
(6H, d, JHH¼6.7 Hz, CH(CH3)2), 1.16 (3H, t, JHH¼7.1 Hz, CH2CH3),
1.83 (1H, m, CH(CH3)2), 3.35 (6H, s, 2NCH3), 3.61 (2H, dd, 3JHH¼6.7,
3
6.7 Hz, NHCH2CH), 4.12 (2H, q, JHH¼7.1 Hz, OCH2), 6.85 (1H, br s,
NH); 13C NMR (100.7 MHz, CDCl3): dC 165.4, 164.8, 162.8, 150.2,
142.9, 60.8, 49.5, 30.5, 29.7, 29.4, 24.9, 19.6, 14.1. Anal. Calcd for
C16H21N3O7 (367.35): C, 52.31; H, 5.76; N,11.44%. Found: C, 52.20; H,
5.71; N, 11.58%.
4.2.4. Methyl 3-(hexylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-oxa-
7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4e). White powder
(0.336 g, 88%); mp 180–182 ꢁC; IR (KBr) (nmax, cmꢀ1): 3346 (N–H),
1797, 1706, 1668, 1637 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 0.81,
4.2.10. Ethyl 3-(hexylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-oxa-
7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4k). White powder
(0.368 g, 93%); mp 94–96 ꢁC; IR (KBr) (nmax, cmꢀ1): 3337 (N–H),
1798, 1702, 1665, 1637 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 0.74
(3H, br s, CH2CH3), 0.84 (3H, br s, OCH2CH3), 1.15–1.19 (8H, m, 4
CH2), 1.44–1.46 (2H, br s, CH2), 3.17 (6H, s, 2NCH3), 3.62 (2H, m,
3
(3H, t, JHH¼6.0 Hz, CH2CH3), 1.25 and 1.54 (8H, 2 m, 4 CH2), 3.28
(6H, s, 2NCH3), 3.62 (3H, s, OCH3), 3.69 (2H, m, NHCH2), 6.66 (1H, br
s, NH); 13C NMR (100.7 MHz, CDCl3): dC 165.3, 164.8, 163.0, 150.3,
142.3, 104.5, 76.8, 51.9, 42.6, 31.5, 31.1, 29.3, 26.1, 22.4, 13.9. Anal.
Calcd for C17H23N3O7 (381.38): C, 53.54; H, 6.08; N, 11.02%. Found:
C, 53.38; H, 6.04; N, 10.94%.
3
NHCH2), 3.95 (2H, q, JHH¼6.8 Hz, OCH2), 6.76 (1H, br s, NH); 13C
NMR (100.7 MHz, CDCl3): dC 165.3, 164.8, 162.5, 150.2, 142.6, 104.7,
77.5, 60.6, 42.4, 31.2, 30.7, 29.0, 26.0, 22.3, 13.9, 13.8. Anal. Calcd for
C18H25N3O7 (395.40): C, 54.68; H, 6.37; N, 10.63%. Found: C, 54.46;
H, 6.30; N, 10.52%.
4.2.5. Methyl
3-(propylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-
oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4f). White powder
(0.305 g, 90%); mp 98–100 ꢁC; IR (KBr) (nmax, cmꢀ1): 3357 (N–H),
1792, 1761, 1689 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 0.95 (3H, t,
3JHH¼7.1 Hz, CH2CH3), 1.59–1.64 (2H, m, CH2CH2CH3), 3.33 (6H, s,
2NCH3), 3.67 (3H, s, OCH3), 3.71 (2H, m, NHCH2CH2), 6.69 (1H, br s,
NH); 13C NMR (100.7 MHz, CDCl3): dC 164.9, 164.8, 163.0, 150.3,
142.6, 104.2, 77.7, 52.0, 44.2, 29.42, 24.1, 10.9. Anal. Calcd for
C14H17N3O7 (339.30): C, 49.56; H, 5.05; N, 12.38%. Found: C, 49.15;
H, 5.02; N, 12.29%.
Acknowledgements
We would like to thank Iran Polymer and Petrochemical In-
stitute (IPPI) Research Council for the financial support.
Supplementary data
4.2.6. Ethyl 3-(1-adamantylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2010.03.058.
1-oxa-7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate
(4g). White
powder (0.405 g, 91%); mp 189–191 ꢁC; IR (KBr) (nmax, cmꢀ1): 3318
(N–H),1799,1685, 1625 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 1.11
3
References and notes
(3H, t, JHH¼7.1 Hz, CH2CH3), 1.61 and 1.65 (6H, AB-system,
3JHH¼14.6 Hz, 3CH2 of adamantyl), 2.05 (6H, s, 3CH2 of ada-
mantyl), 2.08 (3H, s, 3 CH of adamantly), 3.30 (6H, s, 2NCH3), 4.07
(2H, q, 3JHH¼7.1 Hz, OCH2), 7.29 (1H, br s, NH); 13C NMR (100.7 MHz,
CDCl3): dC 164.9, 164.8, 162.8, 150.2, 144.0, 106.5, 77.9, 60.7, 54.8,
42.7, 35.8, 29.7, 29.3, 14.1. Anal. Calcd for C22H27N3O7 (445.46): C,
59.32; H, 6.11; N, 9.43%. Found: C, 59.08; H, 6.16; N, 9.37%.
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4.2.7. Ethyl
3-(allylamino)-7,9-dimethyl-2,6,8,10-tetraoxo-1-oxa-
7,9-diazaspiro[4.5]dec-3-ene-4-carboxylate (4h). White powder
(0.313 g, 89%); mp 139–141 ꢁC; IR (KBr) (nmax, cmꢀ1): 3222 (N–H),
1787, 1687, 1609 (C]O); 1H NMR (400.1 MHz, CDCl3): dH 1.16 (3H, t,
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