Synthesis of indan-based unusual α-amino acid derivatives under phase-transfer catalysis conditions

Article abstract of DOI:10.1021/jo991387v

Conformationally constrained cyclic a-amino acid derivatives were synthesized under solid-liquid phase-transfer catalysis conditions. This methodology involves the bis-alkylation of ethyl isocyanoacetate with various a,a'-dibromo-o-xylene derivatives [a,a'-dibromo-o-xylene 5, 2,3-bis(bromomethyl)-l,4-dimethoxybenzene 6, l,2-bis(bromomethyl)-4,5-dibromobenzene 7,2,3-bis(bromomethyl)naphthalene 8, l,8-bis(bromomethyl)-naphthalene 9, 6,7-bis(bromomethyl)-2,2-dimethyl-lJ/phenalene-l,3(2H)-dione 10,2,3-bis(bromomethyl)-l,4-anthraquinone 11,6,7-bis(bromomethyl)quinoxaline 12, 3,4-bis(bromomethyl)furan 13, l,2,4,5-tetrakis(bromomethyl)benzene 28, and hexakis(bromomethyl)benzene 30] using potassium carbonate as a base and tetrabutylammonium hydrogensulfate as a phase-transfer catalyst to give corresponding isonitrile derivatives, which upon hydrolysis with HC1 in ethanol gave amino esters. Using this method electron-deficient as well as electron-rich and halogen-substituted indan-based a-amino acids were prepared. The preparation of bis-indan as well as tris-indan a-amino esters is also described.

Full text of DOI:10.1021/jo991387v

J . Org. Chem. 2000, 65, 1359-1365
1359
Syn th esis of In d a n -Ba sed Un u su a l r-Am in o Acid Der iva tives
u n d er P h a se-Tr a n sfer Ca ta lysis Con d ition s
Sambasivarao Kotha* and Enugurthi Brahmachary†
Department of Chemistry, Indian Institute of Technology, Powai, Mumbai 400 076, India
Received September 1, 1999
Conformationally constrained cyclic R-amino acid derivatives were synthesized under solid-liquid
phase-transfer catalysis conditions. This methodology involves the bis-alkylation of ethyl isocyano-
acetate with various R,R′-dibromo-o-xylene derivatives [R,R′-dibromo-o-xylene 5, 2,3-bis(bromo-
methyl)-1,4-dimethoxybenzene 6, 1,2-bis(bromomethyl)-4,5-dibromobenzene 7, 2,3-bis(bromomethyl)-
naphthalene 8, 1,8-bis(bromomethyl)-naphthalene 9, 6,7-bis(bromomethyl)-2,2-dimethyl-1H-
phenalene-1,3(2H)-dione 10, 2,3-bis(bromomethyl)-1,4-anthraquinone 11, 6,7-bis(bromomethyl)quin-
oxaline 12, 3,4-bis(bromomethyl)furan 13, 1,2,4,5-tetrakis(bromomethyl)benzene 28, and hexakis-
(bromomethyl)benzene 30] using potassium carbonate as a base and tetrabutylammonium hydro-
gensulfate as a phase-transfer catalyst to give corresponding isonitrile derivatives, which upon
hydrolysis with HCl in ethanol gave amino esters. Using this method electron-deficient as well as
electron-rich and halogen-substituted indan-based R-amino acids were prepared. The preparation
of bis-indan as well as tris-indan R-amino esters is also described.
In tr od u ction
cyclic AAAs (eq 1). Though the BB method provides an
easy access to many cyclic and polycyclic AAAs from
corresponding keto derivatives, the harsh conditions
required for the hydrolysis of the hydantoin intermediate
limits this method to prepare functionalyzed AAAs.
However, recently Kubic et al. reported a mild and facile
hydrolysis of a di-Boc derivative of spirohydantoin under
basic conditions (LiOH/THF/H2O/rt) to give AAAs.5b
Peptide backbone conformation or secondary structure
is crucial in the design of peptide-based therapeutics.1
In this regard R,R-dialkylated amino acids play an
important role in the design of conformationally re-
stricted peptides.2,3 Cyclic R-amino acids4 (AAAs) are
considered as a special class of R,R-dialkylated amino
acids, and surprisingly only the simplest members of this
class had been used in the peptide arena. This is due to
the nonavailability of synthetic methods to deliver com-
plex cyclic AAAs.
Synthetic methods that are available for the prepara-
tion of simple cyclic five- and six-membered AAAs are
not applicable for the preparation of functionalized AAAs.
The traditional Bucherer-Berg (BB) method5 involves
the conversion of a cyclic ketone into a spirohydantoin
under potassium cyanide and ammonium carbonate
conditions. Hydrolysis of the spirohydantoin either in
basic conditions (excess barium hydroxide in water, 140
°C) or in acidic conditions (60% H2SO4, 140 °C) gives
O’Donnell et al.6a developed a simple method for
unusual AAAs synthesis, which involves alkylation of a
Schiff base derived from glycine ester with various
electrophiles, under phase-transfer catalyst (PTC) condi-
tions. Although this method is applicable for simple AAA
derivatives, it was not extended to the synthesis of
complex cyclic AAAs.
The alternate methodology6b for cyclic AAAs involves
intramolecular cyclization of R,R′-dibromo-o-xylenes with
a Schiff base derivative of glycine ethyl ester using
lithium or sodium hexamethyldisilazane (NaHMDS) as
a base during the alkylation step (eq 2). The major
limitation of this method is inapplicability for substrates
† Abstracted from the Ph.D. Thesis of E. Brahmachary, Indian
Institute of Technology-Bombay, 1999.
(1) Giannis, A.; Kolter, T. Angew. Chem., Int. Ed. Engl. 1993, 32,
1244. Hruby, V. J . Biopolymers 1993, 33, 1073. Liskamp, R. M. J .
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Trav. Chim. Pays-Bas 1994, 113, 1. Ondetti, M. A. Annu. Rev.
Pharmacol. 1994, 34, 1.
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molecules 1991, 24, 4004. Tonilolo, C.; Crisma, M.; Formaggio, F.; Valle,
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1991, 31, 1061. Balaram, P. Curr. Opin. Struct. Biol. 1992, 2, 845.
Hruby, V. J .; Al-Obeidi, F.; Kazmierski, W. Biochem. J . 1990, 268, 249.
Paradisi, M. P.; Torrini, I.; Zecchini, G. P.; Lucente, G.; Gavuzzo, E.;
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Science 1989, 244, 182. Bain, J . D.; Diala, E. S.; Glabe, C. G.; Wacker,
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Baker, S. R.; Hancox, T. C. Tetrahedron Lett. 1999, 40, 781. (b) Kubik,
S.; Meissner, R. S.; Rebeck, J ., J r. Tetrahedron Lett. 1994, 35, 6635.
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10.1021/jo991387v CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/11/2000

1360 J . Org. Chem., Vol. 65, No. 5, 2000
Kotha and Brahmachary
having halogens or electron-withdrawing groups in the
aromatic ring. For example, substrates containing electron-
withdrawing groups undergo dimerization reaction via
a single-electron-transfer pathway to give unwanted
dimers (e.g., 1) instead of the alkylation products (e.g.,
2, eq 3).7 A slight modification of the Schiff base method
F igu r e 1.
number of easily available 2-indanone derivatives and
the involvement of the drastic reaction conditions makes
this route less attractive for the preparation of highly
functionalized Ind derivatives. Path b involves bis-
alkylation of glycine or an appropriate glycine equivalent
with R,R′-dibromo-o-xylene 5. Since several R,R′-dibromo-
o-xylene derivatives are easily available or can be pre-
pared from the readily available starting materials, this
route deserves a systematic investigation.
was appeared recently by using solid-supported Schiff
base and 20-fold excess of dibromide and also similar
excess of NaHMDS as a base.8 But this method could
deliver only moderate yields of the coupling product, and
there was no evidence for reactive functional group
tolerance.
Resu lts a n d Discu ssion
Adaptation of approach b to the synthesis of indan-
based AAAs requires preparation of R,R′-dibromo-o-
xylene derivatives as starting materials. All the dibro-
mides (6-13) used in the present study were obtained
by standard/modified literature procedures.
2,3-Bis(bromomethyl)-1,4-dimethoxybenzene 6 was pre-
pared from 2,3-dimethylhydroquinone via the o-methyl-
ation and bromination sequence.12 Similarly, 2,3-bis-
(bromomethyl)naphthalene 8 and 1,8-bis(bromometh-
yl)naphthalene 9 were prepared from the corresponding
dimethylnaphthalenes. 1,2-Bis(bromomethyl)-4,5-dibro-
mobenzene 7 was synthesized starting from o-xylene in
a two-step sequence.13
Among the constrained phenylalanine (Phe) analogs,
indan-based AAAs play a crucial role in the design of a
variety of bioactive peptides.9-11 For example 2-amino-
indan-2-carboxylic acid 3 (Ind) was utilized in the syn-
thesis of molecules with angiotensin II receptor agonistic
and antagonistic activity. In view of the several other
applications of Ind derivatives and problems associated
with the existing methods to generate Ind derivatives
with varying shape, size, and electronic properties, we
sought a process that is not restricted to a simple
substitution pattern and also would be sufficiently flex-
ible to generate various unusual AAAs. In this report we
disclose full details of our facile and simple synthesis of
indan-based unusual AAAs under solid-liquid PTC
conditions using ethyl isocyanoacetate as a glycine
equivalent.
The new phenalene-derived dibromide 10 that was
required for the preparation of highly electron-deficient
pyrene-based AAA was obtained from 1,8-dimethylnaph-
thalene 14 in a two-step sequence. Thus, the reaction of
compound 14 with dimethylmalonyl dichloride in the
presence of aluminum chloride in nitrobenzene gave
compound 15 (45%; mp, 105-107 °C) as a major product
(eq 4). Formation of less-strained six-membered ring
isomer 15 over the other possible five-membered ring
isomers 16 and 17 in the Friedel-Crafts (FC) reaction
is expected to be thermodynamically more favorable.
However, Dolbier et al. have shown that the solvent has
a dramatic effect on the product distribution in FC
reaction of this type of substrates.14 The compound 15
Str a tegy
Toward the synthesis of 2-aminoindan-2-carboxylic
acid 3 (Ind) starting from the preformed benzene deriva-
tives, two possible routes were identified. Alternate
strategies involving benzene ring formation via a cyclo-
addition reaction are not included here. Retrosynthetic
analysis of these routes are shown in Figure 1.
Path a is an example of Bucherer-Berg synthesis of
cyclic AAAs and requires a multistep synthetic sequence
for starting 2-indanone derivatives (e.g., 4). The limited
1
was characterized by its symmetrical H and 13C NMR
spectral data. The other two isomers were also identified
on the basis of 1H NMR spectral data. The reaction of 15
with NBS/AIBN in carbon tetrachloride gave the dibro-
mide 10 (86%; mp, 175-176 °C).
(7) Kotha, S.; Kuki, A. Tetrahedron Lett. 1992, 33, 1569.
(8) Bhandari, A.; J ones, D. G.; Schulleck, J . R.; Vo, K.; Schunk, C.
A.; Tamanaha, L. L.; Chen, D.; Yuan, Z.; Needels, M. C.; Gallop, M. A.
Bioorg. Med. Chem. Lett. 1998, 8, 2303.
Benzylic bromination of known 2,3-dimethylanthra-
quinone15 using NBS gave 2,3-bis(bromomethyl)-1,4-
(9) J osien, H.; Lavielle, S.; Brunissen, A.; Saffroy, M.; Torrens, Y.;
Beaujouan, J .-C.; Glowinski, J .; Chassaing, G. J . Med. Chem. 1994,
37, 1586.
(10) (a) Torrini, I.; Zecchini, G. P.; Paradisi, M.; Lucente, G.; Gauzzo,
E.; Mazza, F.; Pochetti, G.; Spisani, S.; Giuliani, A. L. Int. J . Pept.
Protein Res. 1991, 38, 495. (b) Hsieh, K.-h.; J orgensen, E. C. J . Med.
Chem. 1979, 22, 1038.
(12) Eck, G.; J ulia, M.; Pfeiffer, B.; Rolando, C. Tetrahedron Lett.
1985, 26, 4725.
(13) Pawlowski, G.; Hanack, M. Synthesis 1980, 287. Klingsberg,
E. Synthesis 1972, 29. Gracey, D. E. F.; J ackson, W. R. J . Chem. Soc.
B 1969, 1207.
(14) Dolbier, W. R., J r.; Dulcere, J .-P.; Sellers, S. F.; Koroniak, H.;
Shatkin, B. T.; Clark, T. L. J . Org. Chem. 1982, 47, 2298.
(15) Allen, C. F. H.; Bell, A. Org. Synth. Coll. Vol. 3 1955, 310.
(11) Nolan, W. P.; Ratcliffe, G. S.; Rees, D. C. Tetrahedron Lett. 1992,
33, 6879.

Synthesis of Indan-Based AAAs
J . Org. Chem., Vol. 65, No. 5, 2000 1361
Sch em e 1. i. CNCH2CO2Et, K2CO3, Bu 4NHSO4,
MeCN, ∆. ii. HCl, EtOH
tions leading to the formation of unwanted hydroxy
compounds. By using liquid-liquid PTC conditions (40%
NaOH/PTC/CH2Cl2), formation of dihydroxy or cyclic
ether was observed in some instances. Reaction of R,R′-
dibromo-o-xylene 5 with ethyl isocyanoacetate in the
presence of potassium carbonate and TABHS in aceto-
nitrile gave the required coupling product 19 (Table 1)
in 93% isolated yield.
anthraquinone 11. Similarly, synthesis of quinoxaline
dibromide 12 was achieved from 6,7-dimethylquinoxa-
line.16 The minor product obtained (most likely the
monobromo or tribromo derivative) during the NBS
reaction of 6,7-dimethylquinoxaline was highly unstable
and could not be isolated in a pure form for the spectral
characterization.
Lithium aluminum hydride reduction of dimethyl 3,4-
furandicarboxylate in dry THF gave diol 18.17 Conversion
of diol 18 to dibromide 13 was accomplished by phospho-
rus tribromide/pyridine reaction conditions (eq 5). Re-
cently, Atasoy and co-workers synthesized compound 13
using a different route involving a five-step sequence.17c
Similarly, various dibromo derivatives that have ef-
fectively undergone the cyclization reaction with ethyl
isocyanoacetate under PTC conditions are shown in Table
1.21 In the absence of PTC, only 50% of the product 19
obtained. In some instances the yields are reduced much
more drastically. The coupling products (19-27) were
isolated by a silica gel column as crystalline solids and
1
characterized by their characteristic H and 13C NMR
1
spectral data. In the H NMR spectrum, characteristic
AB quartet resonating in the region of δ 3-4 due to the
diastereotopic methylene hydrogens indicated the forma-
tion of cyclized products. The isonitrile derivatives are
hydrolyzed efficiently in a mild reaction condition (HCl/
ethanol) to give amino esters in good yields. By varying
the hydrolysis conditions, various protected forms of
amino acid derivatives can be obtained.22 For example,
treatment of isocyano esters with HCl in ether at -10
°C will give N-formyl amino esters, whereas N-formyl
amino acids can be obtained under KOH/ethanol/-10 °C
conditions.
In general, the cyclization reaction proceeds well in a
wide range of substrates without any complications. It
is interesting to note that substrates containing electron-
donating (entry 2) and electron-withdrawing groups
(entries 6 and 7) also underwent the alkylation reaction
to give the corresponding isonitrile derivatives. Cycliza-
tion was effective for both five-membered as well as six-
membered ring (entries 5 and 6) formation. Since in
recent years much attention was paid to synthsize amino
acids possessing heterocyclic ring systems for various
biological applications,23,24 we have also extended our
methodology to heterocyclic AAA derivatives (entries 8
and 9). Prior to these reaction conditions, synthesis of
the quinoxaline-based AAA from bromide 12 under
different reaction conditions (KOtBu, 40% aqueous NaOH,
LDA, NaHMDS, KHMDS) gave unacceptable yields of
From the earlier observation, electronically active
dibromo-o-xylene derivatives were found to be sensitive
to several conventional base conditions. In this regard
solid-liquid PTC conditions appeared to be an attractive
solution. Moreover, PTC conditions18 offer an attractive
way of preparing optically active products by using chiral
PTCs.19 After several amino acid synthons were screened,
ethyl isocyanoacetate was realized as a potential glycine
equivalent. It was found that the ethyl isocyanoacetate
can be easily bis-alkylated in the presence of potassium
carbonate as a base and tetrabutylammonium hydrogen-
sulfate (TBAHS) as a PTC to give corresponding isonitrile
derivatives (Scheme 1). It is interesting to note that there
are not many examples known in the literature where
ethyl isocyanoacetate was used as a glycine equivlanet.20
Absence of water in the reaction medium provides an
advantage, which avoids nucleophile substitution reac-
(16) Compound 12 reported as a liquid in the literature: Baudy, R.
B.; Greenblatt, L. P.; J irkovsky, I. L.; Conklin, M.; Russo, R. J .;
Bramlett, D. R.; Emrey, T. A.; Simmonds, J . T.; Kowal, D. M.; Stein,
R. P.; Tasse, R. P. J . Med. Chem. 1993, 36, 331.
(17) (a) Cook, M. J .; Frobes, E. J . Tetrahedron 1968, 24, 4501. (b)
Reduction of diethyl 3,4-furandicarboxylate to diol 18, see: J enneskens,
L. W.; Kostermans, G. B. M.; ten Brink, H. J .; de Wolf, W. H.;
Bickelhaupt, F. J . Chem. Soc., Perkin Trans 1 1985, 2121. (c) Atasoy,
B.; Ozen, R. Tetrahedron 1997, 53, 13867.
(18) Starks, C. M.; Liotta, C. Phase Transfer Catalysis: Principles
and Techniques; Academic Press: New York, 1978. Weber, W. B.;
Gokel, G. W. Phase Transfer Catalysis in Organic Synthesis; Springer-
Verlag: Berlin, 1977. Sirovski, F.; Reichardt, C.; Gorokhova, M.;
Ruban, S.; Stoikova, E. Tetrahedron 1999, 55, 6363 and references cited
therein.
(19) O’Donnell, M. J .; Bennett, W. D.; Wu, S. J . Am. Chem. Soc.
1989, 111, 2353. O’Donnell, M. J .; Wu, S.; Huffman, J . C. Tetrahedron
1994, 50, 4507.
(20) (a) For reviews on the synthetic utility of R-metalated isocy-
anides, see: Hoppe, D. Angew. Chem., Int. Ed. Engl. 1974, 13, 789.
Schollkopf, U.; Hoppe, D.; J entsch, R. Chem. Ber. 1975, 108, 1592. (b)
Ramalingam, K.; Kalvin, D.; Woodward, R. W. J . Lebel. Comp. 1984,
21, 833. Kalvin, D., Ramalingam, K.; Woodward, R. W. Synth.
Commun. 1985, 15, 267.
(21) For preliminary communication of this work, see: Kotha, S.;
Brahmachary, E. Bioorg. Med. Chem. Lett. 1997, 7, 2719.
(22) Schollkopf, U.; Hoppe, D.; J entsch, R. Angew. Chem., Int., Ed.
Engl. 1971, 10, 331.
(23) Horwell, D. C.; McKiernan, M. J .; Osborne, S. Tetrahedron Lett.
1998, 39, 8729; Ma, C.; Liu, X.; Zhao, S.; Cook, J . M. Tetrahedron Lett.
1999, 40, 660. Franceschetti, L.; Garzon-Aburbeh, A.; Mahmoud, M.
R.; Natalini, B.; Pellicciari, R. Tetrahedron Lett. 1993, 34, 3185.
Bennett, F. A.; Barlow, D. J .; Dodoo, A. N. O.; Hider, R. C.; Lansley,
A. B.; Lawrence, M. J .; Marriott, C.; Bansal, S. S. Tetrahedron Lett.
1997, 38, 7449.

1362 J . Org. Chem., Vol. 65, No. 5, 2000
Kotha and Brahmachary
Ta ble 1. Syn th esis of Cyclic r-Am in o Acid Der iva tives u n d er P h a se-Tr a n sfer Ca ta lyst Con d ition s
the coupling products (<5%). Usage of various amino acid
synthons also met with no or little success. Finally by
using solid-liquid PTC conditions, a highly base-sensi-
tive dibromide 12 gave the required product 26 in 40%
yield.25 Since furan can undergo various cycloaddition
reactions,26 the derivative 27 may serve as a useful
synthon for the generation of several other constrained
AAA derivatives.

Synthesis of Indan-Based AAAs
J . Org. Chem., Vol. 65, No. 5, 2000 1363
In the case of the tetrakis(bromomethyl)benzene 28,
two coupling products were obtained in 1:1 ratio, which
were isolated by a silica gel column in 42% combined
yield (eq 6). Both compounds (29a and 29b) gave almost
demonstrated via synthesis of simple as well as complex
AAA derivatives. Moreover, commercial availability of
ethyl isocyanoacetate combined with the operational
simplicity makes this methodology extremely attractive
for the preparation of highly functionalized AAAs. The
ability to prepare electronically interesting AAAs will
open the door to chemical, biological, and medicinal
applications of unnatural AAAs.
1
identical H and 13C NMR spectral data, and tentatively
we concluded that they are cis/trans isomers. Indepen-
dent hydrolysis of both isomers gave amino esters whose
1H NMR spectra are again identical in nature.
Exp er im en ta l Section
Melting points are uncorrected. Infrared spectra were
recorded as KBr wafers unless mentioned otherwise. UV
spectra were taken using chloroform as a solvent. 1H NMR
spectra were recorded at 300 or 60 MHz, and 13C NMR spectra
were recorded at 75.4 MHz. Samples were made in chloro-
form-d solvent, and chemical shifts were reported in δ scale
using tetramethylsilane as the internal standard. Coupling
constants J are in hertz (Hz). Analytical thin-layer chroma-
tography (TLC) was performed on glass plates coated with
Acme’s silica gel G or GF 254 (containing 13% calcium sulfate
as a binder). Visualization of the spots on the TLC plates was
achieved by exposure either to iodine vapor or to UV light.
Flash chromatography was performed using Acme’s silica gel
(100-200 mesh), and the column was usually eluted with
hexane-ethyl acetate mixture. Acetonitrile and carbon tetra-
chloride were distilled over phosphorous pentoxide. Dry THF
and ether were obtained by distillation over sodium benzophe-
none ketyl. For all the reactions dry magnesium sulfate was
used as a drying agent after workup. Yields refer to the
chromatographically isolated yields. N-Bromosuccinimide was
freshly crystallized from hot water and dried under vacuum
over P2O5 for 3 h. Ethyl isocyanoacetate, R,R′-dibromo-o-xylene
5, tetrakis(bromomethyl)benzene 28, hexakis(bromomethyl)-
benzene 30, 4,5-dimethylphenalenediamine, 2,3-dimethylhy-
droquinone, dimethyl 3,4-furnadicarboxylate, 1,8-dimethyl-
naphthalene 14, and dimethylmalonyl chloride were purchased
from Aldrich Chemical Co. 2,3-Dimethyl naphthalene and
lithium aluminum hydride were obtained from Lancaster
Synthesis. All the commercial grade reagents were used
without further purification.
Gen er a l P r oced u r e for t h e Bis-a lk yla t ion of E t h yl
Isocya n oa ceta te. To a solution of ethyl isocyanoacetate (1
mmol) in acetonitrile (20 mL) were added finely grounded
potassium carbonate (6 mmol), TBAHS (0.2 mmol), and
electrophile (1 mmol). The resulting heterogeneous mixture
was heated at 70-80 °C until all the starting electrophile had
been consumed (TLC monitoring). Then, the reaction mixture
was cooled and filtered through a cintered glass crucible to
remove the unwanted salts. Then the solid material was
washed with acetonitrile, and the filtrate was evaporated on
a rotary evaporator under reduced pressure. The residue
obtained was taken in ether and washed with water and brine
and then dried. The solvent was evaporated, and the crude
product was purified by silica gel column chromatography.
Analytical samples were obtained by recrystallization from
hexane and ethyl acetate mixture.
Treatment of hexakis(bromomethyl)benzene 30 with
ethyl isocyanoacetate under PTC conditions gave two
trisindan derivaties (3:1, eq 7). Unlike the above indacene
isomers, in this case both the stereochemically different
isomers 31 and 32 could be distinguished by their 1H
NMR spectral data. The major isomer 31 (mp, 148-149
°C), isolated by a silica gel column, was confirmed by its
1H NMR spectrum as an unsymmetrical compound. In
the 1H NMR spectrum, compound 31 gave a complex ABq
resonating at δ 3.32 due to the diastereotopic methylene
protons and a mixture of two triplets (2:1 ratio) and two
quartets (2:1) due to ethyl ester functionality, suggesting
its unsymmetrical nature. Compound 32 (mp, 120-121
°C) showed a symmetrical ABq due to methylene protons
and a clean triplet and a quartet due to ethyl ester
functionality in the 1H NMR spectrum. Hydrolysis of
these two isonitrile derivatives in a separate experiment
gave amino esters as liquids in 80% yield. In view of
recent developments in the utilization of multiarmed
AAAs in the design and synthesis of new ligands and
functional dendrimers, bis and tris-armed amino acid
derivatives reported here may find interesting applica-
tions in chemical and allied sciences.27
Con clu sion s
In summary, we have shown that ethyl isocyanoacetate
can be effectively bis-alkylated under solid-liquid PTC
conditions with the readily available R,R′-dibromo-o-
xylene derivatives. The flexibility of the method has been
P r eca u tion : Ethyl isocyanoacetate and electrophiles used
in this study are lacrymators and irritants and must be
handled with proper care. Some of them are also potent
mutagens.
Gen er a l P r oced u r e for H yd r olysis of t h e Cou p lin g
P r od u ct. To a solution of the coupling product (1 mmol) in
absolute ethanol (5 mL) were added a few drops of concen-
trated hydrochloric acid, and the reaction mixture was stirred
at room temperature for a few hours. Ethanol was evaporated
under reduced pressure, the remaining hydrochloride salt was
dissolved in water and extracted with ether to remove un-
wanted organic residues, and the ether layer was discarded.
Then the aqueous layer was brought to pH ) 9-10 by addition
of NH4OH solution and then extracted with ethyl acetate.
Combined ethyl acetate extract was washed with water and
brine and dried. Removal of the solvent at reduced pressure
gave amino ester.
(24) Tamiaki, H.; Onishi, M. Tetrahedron: Asymmetry 1999, 10,
1029. Beecher, J . E.; Tirrell, D. A. Tetrahedron Lett. 1998, 39, 3927.
Yokum, T. S.; Tungaturthi, P. K.; McLaughlin, M. L. Tetrahedron Lett.
1997, 38, 5111. Imperiali, B.; Prins, T. J .; Fisher, S. L. J . Org. Chem.
1993, 58, 1613. Zhang, J .; Clive, D. L. J . J . Org. Chem. 1999, 64, 1754.
(25) Kotha, S.; Brahmachary, E.; Kuki, A.; Lang, K.; Anglos, D.;
Singaram, B.; Chrismann, W. Tetrahedron Lett. 1997, 38, 9031.
(26) Kappe, C. O.; Murphree, S. S.; Padwa, A. Tetrahedron 1997,
53, 14179.
(27) Basu, B.; Frejd, T. Acta Chim. Scand. 1996, 50, 316. Ritzen,
A.; Basu, B.; Chattopadhyay, S. K.; Dossa, F.; Frejd, T. Tetrahedron:
Asymmetry 1998, 9, 503. Kayser, B.; Altman, J .; Beck, W. Tetrahedron
1997, 53, 2475. Kayser, B.; Altman, J .; Beck, W. Chem. Eur. J . 1999,
5, 754. Chow, H.-F.; Mong, T. K.-K.; Nongrum, M. F.; Wan, C.-W.
Tetrahedron 1998, 54, 8543.

1364 J . Org. Chem., Vol. 65, No. 5, 2000
Kotha and Brahmachary
Eth yl 2-Isocya n oin d a n -2-ca r boxyla te (19). Prepared
from R,R′-dibromo-o-xylene 5 in 93% isolated yield as white
crystalline needles. Mp, 60-62 °C. IR (KBr): ν 2139, 1746
cm-1. UV (CHCl3): λmax nm (ꢀ M-1 cm-1) 273 (1810), 266 (1862).
1H NMR: δ 1.35 (t, J ) 7.2, 3H), 3.47 (1/2 ABq, J ) 16.0, 2H),
3.69 (1/2 ABq, J ) 16.3, 2H), 4.32 (q, J ) 7.2, 2H), 7.25 (s, 4H).
13C NMR: δ 14.0, 46.3, 63.1, 67.9, 124.6, 127.7, 137.9, 158.6,
168.6. MS: m/e 251 (M+). Anal. Calcd for C13H13NO2: C, 72.54;
H, 6.08; N, 6.51. Found: C, 72.94; H, 6.05; N, 6.86. Hyd r olysis
magnetic bar and nitrogen inlet and outlet was charged with
freshly sublimed AlCl3 (750 mg, 5.62 mmol). Then dry ni-
trobenzene (4 mL) was introduced, and the mixture was stirred
at 20 °C for 5 min. To the resulting greenish yellow reaction
mixture, a solution of dimethyl malonyldichloride (375 mg,
2.21 mmol) in dry nitrobenzene (1.5 mL) was added and stirred
for another 5 min. Then 1,8-dimethylnaphthalene 14 (300 mg,
1.92 mmol) was added in small portions with the help of a
solid addition funnel during a period of 1/2 h, and stirring was
continued for 1.5 h. Then the mixture was poured into an ice
cold solution of 1 N HCl (30 mL) at 0 °C. After the solution
was stirred for 5 min with dichloromethane (30 mL), the layers
were separated and the aqueous layer was extracted with
dichloromethane. The combined organic layers were washed
with water and brine and then dried. The solvent was
evaporated, and from the residue excess of nitrobenzene was
removed by vacuum distillation. The crude product was
chromatographed on a silica gel column by eluting with
hexane-ethyl acetate mixture (1:4) to give the first compound
16 5%. Mp, 120-122 °C. IR (KBr): ν 1730, 1696 cm-1. This
was followed by the second isomer 17 (33%, mp, 136-138 °C).
IR (KBr): ν 1700, 1666 cm-1. 1H NMR: δ 1.34 (s, 6H), 3.03 (s,
3H), 3.39 (s, 3H), 7.48-7.56 (m, 2H), 7.89-7.92 (m, 1H), 8.33
(s, 1H). MS: m/e 252 (M+). Further elution of the column gave
the required symmetrical dione 15 (45%, mp, 105-107 °C).
IR (KBr): ν 1697, 1666 cm-1. 1H NMR: δ 1.48 (s, 6H), 3.52 (s,
6H), 7.51 (1/2 ABq, J ) 7.5, 2H), 8.26 (1/2 ABq, J ) 7.5, 2H).
13C NMR: δ 22.6, 26.8, 57.9, 126.1, 128.5, 130.1, 132.3, 133.0,
143.5, 199.3. MS: m/e 252 (M+). Anal. Calcd for C17H16O2:
80.92; H, 6.39. Found: C, 80.93; H, 6.25.
p r od u ct: Colorless liquid, 90%. IR (neat): ν 3350, 1725 cm-1
.
1H NMR: δ 1.28 (t, J ) 7.1, 3H), 1.81 (s, 2H), 2.92 (1/2 AXq,
J ) 15.6, 2H), 3.57 (1/2 AXq, J ) 16.1, 2H), 4.22 (q, J ) 7.1,
2H), 7.23 (m, 4H).
E t h yl 4,7-Dim et h oxy-2-isocya n oin d a n -2-ca r b oxyla t e
(20). Prepared from 2,3-bis(bromomethyl)-1,4-dimethoxyben-
zene 6 as colorless plates in 57% yield. Mp, 97-98 °C. IR
(KBr): ν 2133, 1749, 1255 cm-1. UV (CHCl3): λmax nm (ꢀ M-1
cm-1) 281 (3550), 248 (2630). 1H NMR: δ 1.34 (t, J ) 7.1, 3H),
3.48 (1/2 ABq, J ) 16.5, 2H), 3.61 (1/2 ABq, J ) 16.6, 2H), 3.78
(s, 6H), 4.31 (q, J ) 7.1, 2H), 6.69 (s, 2H). 13C NMR: δ 13.9
(q), 44.0 (t), 55.5 (q), 63.0 (t), 67.7 (s), 109.9 (d), 127.4 (s), 149.9
(s), 158.3 (s), 168.6 (s). MS: m/e 275 (M+). Anal. Calcd for
C
15H17NO4: C, 65.44; H, 6.22; N, 5.08. Found: C, 65.91; H,
6.02; N, 5.13. Hyd r olysis p r od u ct: Light yellow liquid, 88%.
1
IR (neat): ν 3373, 1727, 1257 cm-1. H NMR: δ 1.27 (t, J )
7.1, 3H), 2.77 (br s, 2H), 3.08 (1/2 AXq, J ) 16.6, 2H), 3.48 (1/2
AXq, J ) 16.5, 2H), 3.76 (s, 6H), 4.22 (q, J ) 7.1, 2H), 6.65 (s,
2H).
Eth yl 4,5-Dibr om o-2-isocyan oin dan -2-car boxylate (21).
Prepared from 1,2-bis(bromomethyl)-4,5-dibromobenzene 7 as
a white crystalline solid in 65% yield. Mp, 59-60 °C. IR
6,7-Bis(br om om eth yl)-2,2-d im eth yl-1H-p h en a len e-1,3-
(2H)-d ion e (10). To a solution of dimethyl phenalene dione
derivative 15 (252 mg, 1 mmol) and AIBN (15 mg) in carbon
tetrachloride (14 mL) was added N-bromosuccinimide (391 mg,
2.2 mmol). The reaction mixture was refluxed for 3 h. Then
the flask was cooled in an ice bath and the insoluble succin-
imide was filtered off. Then the filtrate was concentrated on
a rotary evaporator. Crystallization of the crude product from
hexane and carbon tetrachloride afforded 10 as light brown
crystalline needles in 86% yield. Mp, 175-176 °C. IR (KBr):
1
(KBr): ν 2139, 1741 cm-1. H NMR: δ 1.36 (t, J ) 7.1, 3H),
3.41 (1/2 ABq, J ) 16.5, 2H), 3.64 (1/2 ABq, J ) 16.6, 2H), 4.33
(q, J ) 7.1, 2H), 7.52 (s, 2H). 13C NMR: δ 14.0, 45.4, 63.4,
68.1, 123.8, 129.7, 139.1, 159.7, 167.7; MS: m/e 373 (M+). Anal.
Calcd for C13H11NO2Br2: C, 41.85; H, 2.97; N, 3.75. Found:
C, 41.85; H, 2.99; N, 3.51. Hyd r olysis p r od u ct: White
crystalline solid, 93%. MP, 86-87 °C. IR (KBr): ν 3372, 1725.
1H NMR: δ 1.29 (t, J ) 7.1, 3H), 1.68 (br s, 2H), 2.81 (1/2 AXq,
J ) 16.1, 2H), 3.47 (1/2 AXq, J ) 16.3, 2H), 4.22 (q, J ) 7.1,
2H), 7.47 (s, 2H).
1
ν 1701, 1670 cm-1. H NMR: δ 1.51 (s, 6H), 5.29 (s, 4H), 7.86
Eth yl 3-Isocya n o-2,3-d ih yd r o-4H-cyclop en ta [b]n a p h -
th a len e-3-ca r boxyla te (22). Obtained as colorless plates
from 2,3-bis(bromomethyl)naphthalene 8 in 65% yield. Mp,
138-139 °C. IR (KBr): ν 2140, 1746 cm-1. UV (CHCl3): λmax
(1/2 ABq, J ) 7.5, 2H), 8.42 (1/2 ABq, J ) 7.5, 2H). 13C NMR:
δ 22.5, 35.2, 58.5, 128.9, 129.1, 133.1, 133.5, 134.0, 140.2, 198.4.
MS: m/e 410 (M+). Anal. Calcd for C17H14Br2O2: C, 49.78; H,
3.44. Found: C, 49.64; H, 3.31.
1
nm (ꢀ M-1 cm-1) 321 (1890), 271 (3590). H NMR: δ 1.36 (t,
Eth yl 2-Isocya n o-1,2,3,6,7,8-h exa h yd r o-7,7-d im eth yl-
6,8-d ioxop yr en e-2-ca r boxyla te (24). Prepared from dibro-
mide 10 as a light brown needles in 40% isolated yield. Mp,
172-173 °C. IR (KBr): ν 2140, 1740, 1703 cm-1. UV (CHCl3):
J ) 7.1, 3H), 3.6 (1/2 ABq, J ) 16.0, 2H), 3.83 (1/2 ABq, J )
16.3, 2H), 4.34 (q, J ) 7.1, 2H), 7.45 (dd, J ) 6.3, 3.1, 2H),
7.70 (s, 2H), 7.80 (dd, J ) 6.2, 3.3, 2H). 13C NMR: δ 14.0, 45.6,
63.2, 68.6, 123.2, 125.8, 127.7, 133.3, 136.5, 158.9, 168.3. MS:
m/e 265 (M-1). Anal. Calcd for C17H15NO2: C, 76.96; H, 5.99;
N, 5.28. Found: C, 76.89; H, 6.06; N, 5.09. Hyd r olysis
p r od u ct: White crystalline solid, 96%. Mp, 75-76 °C. IR
1
λmax nm (ꢀ M-1 cm-1) 338 (1940), 248 (2190). H NMR: δ 1.33
(t, J ) 7.1, 3H), 1.53 (d, J ) 2.0, 6H), 3.68 (1/2 ABq, J ) 16.3,
2H), 3.82 (1/2 ABq, J ) 16.6, 2H), 4.38 (q, J ) 7.1, 2H), 7.60 (d,
J ) 7.3, 2H), 8.41 (d, J ) 7.5, 2H). 13C NMR: δ 14.0, 22.4,
23.2, 40.1, 58.7, 61.4, 63.6, 126.5, 127.3, 129.0, 131.1, 136.6,
1
(KBr): ν 3367, 1722 cm-1. H NMR: δ 1.39 (t, J ) 7.1, 3H),
1.67 (s, 2H), 3.03 (1/2 AXq, J ) 16.1, 2H), 3.68 (1/2 AXq, J )
16.1, 2H), 4.25 (q, J ) 7.1, 2H), 7.41 (m, 2H), 7.66 (s, 2H),
7.74 (m, 2H).
160.2, 167.5, 198.7. MS: m/e 361 (M+). Anal. Calcd for C17H15
-
NO2: C, 73.05; H, 5.29; N, 3.86. Found: C, 72.88; H, 5.16; N,
3.69. Hyd r olysis p r od u ct: White solid, 90%. Mp, 180 °C (dec).
Eth yl 2-Isocya n o-2,3-d ih yd r o-1H-p h en a len e-2-ca r box-
yla te (23). Prepared from 1,8-bis(bromomethyl)naphthalene
9 as a colorless crystalline solid in 89% yield. Mp, 74-75 °C.
IR (KBr): ν 2135, 1743 cm-1. UV (CHCl3): λmax nm (ꢀ M-1
1
IR (KBr): ν 3360, 1745, 1700 cm-1. NMR: δ 1.20 (t, J )
7.1, 3H), 1.49 (s, 3H), 1.51 (s, 3H), 1.90 (br s, 2H), 3.35 (1/2
AXq, J ) 16.4, 2H), 3.72 (1/2 AXq, J ) 16.4, 2H), 4.19 (q, J )
7.1, 2H), 7.55 (1/2 ABq, J ) 7.5, 2H), 8.37 (1/2 ABq, J ) 7.3,
2H).
1
cm-1) 284 (1340), 277 (2650) nm. H NMR: δ 1.34 (t, J ) 7.1,
3H), 3.53 (1/2 ABq, J ) 15.5, 2H), 3.69 (1/2 ABq, J ) 15.7, 2H),
4.33 (q, J ) 7.1, 2H), 7.30 (d, J ) 6.9, 2H), 7.44 (t, J ) 7.1,
2H), 7.77 (t, J ) 8.2, 2H). 13C NMR: δ 13.9 (q), 39.8 (t), 61.6
(s), 63.0 (t), 125.5 (d), 125.9 (d), 127.3 (d), 127.8 (s), 129.1 (s),
133.2 (s), 158.8 (s), 168.3 (s). MS: m/e 265 (M+). Anal. Calcd
for C17H15NO2: C, 76.96; H, 5.99; N, 5.28. Found: C, 76.82;
H, 5.84; N, 5.42. Hyd r olysis p r od u ct: Colorless liquid, 92%.
IR (KBr): ν 3374, 1730 cm-1. 1H NMR: δ 1.25 (t, J ) 7.1, 3H),
1.62 (s, 2H), 1.15 (1/2 AXq, J ) 15.3, 2H), 3.61 (1/2 AXq, J )
15.7, 2H), 4.21 (q, J ) 7.1, 2H), 7.26 (m, 2H), 7.41 (m, 2H),
7.71 (m, 2H).
Eth yl 3-Isocya n o-2,3-d ih yd r o-4H-cyclop en ta [b]-6,11-
a n th r a qu in on e-3-ca r boxyla te (25). Prepared from 2,3-bis-
(bromomethyl)-1,4-anthraquinone 11 as a yellow crystalline
solid in 45% yield. Mp, 207-208 °C. IR (KBr): ν 2138, 1746,
1671 cm-1; UV (CHCl3): λmax nm (ꢀ M-1 cm-1) 326 (1150), 260
(1810). 1H NMR: δ 1.38 (t, J ) 7.1, 3H), 3.65 (1/2 ABq,
J ) 17.0, 2H), 3.84 (1/2 ABq, J ) 17.0, 2H), 4.38 (q, J ) 7.1,
2H), 7.82 (dd, J ) 5.6, 3.2, 2H), 8.21 (s, 2H), 8.32 (dd, J ) 5.6,
3.2, 2H). Anal. Calcd for C21H15NO4: C, 73.03; H, 4.38; N, 4.05.
Found: C, 73.18; H, 4.09; N, 4.06. Hyd r olysis p r od u ct: Light
yellow solid, 66%. Mp, 220-222 °C. IR (neat): ν 3355, 1724,
F r ied el-Cr a fts Rea ction of 1,8-Dim eth yln a p h th a len e.
A 20 mL three-necked round-bottomed flask equipped with a
1
1670 cm-1. H NMR: δ 1.31 (t, J ) 7.1, 3H), 1.65 (br s, 2H),

Synthesis of Indan-Based AAAs
J . Org. Chem., Vol. 65, No. 5, 2000 1365
3.06 (1/2 AXq, J ) 16.8, 2H), 3.66 (1/2 AXq, J ) 16.3, 2H), 4.25
(q, J ) 7.1, 2H), 7.78 (m, 2H), 8.16 (s, 2H), 8.3 (m, 2H).
Eth yl 7-Isocya n o-6,7-d ih yd r o-8H-cyclop en ta [g]qu in ox-
a lin e-7-ca r boxyla te (26). Prepared from 2,3-bis(bromometh-
yl)quinoxaline 12 as a light brown solid in 40% yield. Mp, 110-
112 °C. IR (KBr): ν 2137, 1736 cm-1. UV (CHCl3): λmax nm (ꢀ
M-1 cm-1) 323 (81890), 245 (5030). 1H NMR: δ 1.38 (t, J )
7.1, 3H), 3.71 (1/2 ABq, J ) 16.8, 2H), 3.90 (1/2 ABq, J ) 16.8,
2H), 4.36 (q, J ) 7.1, 2H), 7.98 (s, 2H), 8.82 (s, 2H). 13C NMR:
δ 13.9, 45.6, 63.4, 68.5, 124.7, 141.4, 142.9, 144.6, 159.8, 167.7.
MS: m/e 277 (M+). Anal. Calcd for C15H13N3O2: C, 67.40; H,
4.90; N, 15.72. Found: C, 67.77; H, 4.83; N, 15.29. Hyd r olysis
15.0, 4H), 4.21 (q, J ) 7.3, 4H), 7.06 (s, 2H). Com p ou n d 29b:
21%; mp, 152-154 °C. IR (KBr): ν 2135, 1734 cm-1. UV
(CHCl3): λmax nm (ꢀ M-1 cm-1) 283 (2270), 278 (2300). 1H
NMR: δ 1.35 (t, J ) 7.1, 6H), 3.35 (1/2 ABq, J ) 15.6, 4H),
3.67 (1/2 ABq, J ) 15.7, 4H), 4.31 (q, J ) 7.1, 4H), 7.11 (s, 2H).
13C NMR: δ 14.7 (q), 46.4 (t), 63.9 (t), 68.8 (s), 121.5 (d), 138.5
(s), 159.6 (s), 169.1 (s). MS: m/e 352 (M+). Hyd r olysis
p r od u ct: White crystalline solid, 64%. Mp, 123-125 °C. IR
1
(KBr): ν 3350, 1725 cm-1. H NMR: δ 1.29 (t, J ) 7.1, 6H),
1.69 (br s, 4H), 2.81 (1/2 AXq, J ) 15.2, 4H), 3.52 (1/2 AXq, J )
15.2, 4H), 4.21 (q, J ) 7.1, 4H), 7.06 (s, 2H).
Tr ieth yl 2,5,8-Tr iisocya n o-2,5,8-tr iin d a n tr ica r boxyla te
(31 a n d 32). Prepared from hexakis(bromomethyl)benzene 30.
Two isomers were formed in 1:2 ratio as crystalline solids in
30% combined yield. Major isomer 31 (unsymmetrical): mp,
148-149 °C. IR (KBr): ν 2142, 1729, 1743 cm-1. UV (CHCl3):
1
p r od u ct: White solid, 94%. IR (KBr): ν 3357, 1720 cm-1. H
NMR: δ 1.27 (t, J ) 7.1, 3H), 1.88 (s, 2H), 3.08 (1/2 AXq, J )
16.6, 2H), 3.71 (1/2 AXq, J ) 16.8, 2H), 4.22 (q, J ) 7.1, 2H),
7.87 (s, 2H), 8.71 (s, 2H).
Eth yl 4-Isocya n o-3,4-d ih yd r o-5H-cyclop en ta [c]fu r a n -
4-ca r boxyla te (27). Prepared from 3,4-bis(bromomethyl)furan
13 as a white solid in 67% yield. Mp, 40-42 °C. IR (KBr): ν
1
λmax nm (ꢀ M-1 cm-1) 360 (680), 234 (1590). H NMR: δ 1.36
(t, J ) 7.3, 6H), 1.37 (t, J ) 7.1, 3H), 3.32 (m, 6H), 3.63 (t,
J ) 15.7, 6H), 4.34 (q, J ) 7.1, 4H), 4.36 (q, J ) 7.1, 2H). 13C
NMR: δ 14.0 (2C), 44.6, 44.7 (2C), 63.4 (2C), 68.0, 68.4, 134.0
(3C), 159.2, 159.5, 167.9, 168.1. HRMS: m/e for C27H27N3O6
Calcd 489.1899; found 489.1907. Hyd r olysis p r od u ct: Color-
2138, 1740 cm-1 1H NMR: δ 1.35 (t, J ) 7.1, 3H), 3.22 (1/2
.
ABq, J ) 15.9, 2H), 3.41 (1/2 ABq, J ) 15.9, 2H), 4.32 (q, J )
7.1, 2H), 7.18 (s, 2H). 13C NMR: δ 14.0, 37.8, 68.0, 126.8, 134.5,
159.6, 167.9. MS: m/e 205 (M+). Hyd r olysis p r od u ct: Light
less liquid, 85%. IR (neat): ν 3350, 1725 cm-1 1H NMR: δ
.
1
yellow liquid, 78%. IR (KBr): ν 3367, 1725 cm-1. H NMR: δ
1.29 (m, 9H), 1.92, (s, 6H), 2.76 (m, 6H), 3.45 (m, 6H), 4.22 (q,
J ) 7.3, 6H). Minor isomer 32 (symmetrical): mp, 120-121
°C. IR (KBr): ν 2140, 1748 cm-1. UV (CHCl3): λmax nm (ꢀ M-1
cm-1) 270 (7210), 241 (1720). 1H NMR: δ 1.36 (t, J ) 7.1, 9H),
3.46 (1/2 ABq, J ) 15.9, 6H), 3.59 (1/2 ABq, J ) 15.7, 6H), 4.32
(q, J ) 7.1, 6H). Hyd r olysis p r od u ct: Colorless liquid, 80%.
1.22 (t, J ) 6.9, 3H), 2.37 (s, 2H), 2.64 (1/2 ABq, J ) 16.5, 2H),
3.17 (1/2 ABq, J ) 15.9, 2H), 4.16 (q, J ) 6.9, 2H), 7.06 (s, 2H).
Dieth yl 2,6-Diisocyan o-1,2,3,5,6,7-s-h exah ydr oin dacen e-
2,6-d ica r boxyla te (29a a n d 29b). Two isomers were formed
from 1,2,4,5-tetrakis(bromomethyl)benzene 28 as crystalline
solids in 42% combined yield. Com p ou n d 29a : 21%; mp, 166-
168 °C. IR (KBr): ν 2137, 1742 cm-1. UV (CHCl3): λmax nm (ꢀ
M-1 cm-1) 284 (2836), 277 (3390). 1H NMR: δ 1.35 (t, J ) 7.1,
6H), 3.42 (1/2 ABq, J ) 15.6, 4H), 3.66 (1/2 ABq, J ) 15.7, 4H),
4.33 (q, J ) 7.1, 4H), 7.12 (s, 2H). 13C NMR: δ 14.6 (q), 46.4
(t), 63.8 (t), 69.2 (s), 121.6 (d), 138.4 (s), 159.4 (s), 168.9 (s).
MS: m/e 352 (M+). Anal. Calcd for C20H20N2O4: C, 68.16; H,
5.71; N, 7.95. Found: C, 68.18; H, 5.83; N, 7.79. Hyd r olysis
p r od u ct: White crystalline solid, 67%. Mp, 91-93 °C. IR
IR (neat): ν 3350, 1725 cm-1 1H NMR: δ 1.29 (t, J ) 6.9,
.
9H), 1.98 (s, 6H), 2.75-2.85 (m, 6H), 3.37-3.77 (m, 6H), 4.22
(q, J ) 7.3, 6H).
Ack n ow led gm en t. We thank DST-New Delhi for
the financial support. We are grateful to RSIC-Mumbai
for the spectral data. E.B. thanks CSIR-New Delhi for
the fellowship.
1
(KBr): ν 3348, 1724 cm-1. H NMR: δ 1.29 (t, J ) 7.3, 6H),
1.72 (s, 4H), 2.81 (1/2 AXq, J ) 15.0, 4H), 3.48 (1/2 AXq, J )
J O991387V