A novel synthetic approach towards N-phenylsuccinimides from γ-lactam-2-carboxylic acid derivatives by reaction with CAN-NaBrO3

Article abstract of DOI:10.1016/j.tetlet.2007.12.071

N-Arylsuccinimides have been synthesized by decarboxylative oxidation of N-aryl-γ-lactam-2-carboxylic acids with the dual oxidant CAN/NaBrO₃ in refluxing acetonitrile-water.

Full text of DOI:10.1016/j.tetlet.2007.12.071

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1405–1407
A novel synthetic approach towards N-phenylsuccinimides from
c-lactam-2-carboxylic acid derivatives by reaction with CAN–NaBrO3
Gopa Barman, Mahuya Roy, Jayanta. K. Ray *
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
Received 4 October 2007; revised 4 December 2007; accepted 12 December 2007
Available online 14 January 2008
Abstract
N-Arylsuccinimides have been synthesized by decarboxylative oxidation of N-aryl-c-lactam-2-carboxylic acids with the dual oxidant
CAN/NaBrO3 in refluxing acetonitrile–water.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Dual oxidant; Decarboxylative oxidation; N-Arylsuccinimides; Radical cation
1. Introduction
replenished by the action of the bromate. Using this sys-
tem, hydroquinones are oxidized to quinones, sulfides to
sulfoxides and arylmethanols are transformed into the cor-
responding carbonyl compounds in good yields.6,7 Loudon
et al. reported that oxidative decarboxylation of amino
acids with [bis(trifluoroacetoxy)iodo]benzene in the pres-
ence of pyridine gives the corresponding aldehyde in about
45% yield.8 In 1988, Ochiai and Moriaty et al. found that
oxidation of L-proline with iodosobenzene (ISB) gave 2-
pyrrolidinone under neutral conditions.9 The reaction of the
c-lactam-carboxylic acids 1 with CAN–NaBrO3 in aceto-
nitrile–water (1:1; v/v) at 80 °C furnished exclusively the
1,3-diaryl succinimides 2 in high yields (Scheme 1, Table 1).
The starting materials for this study, c-lactam-2-carboxylic
acids 1, were synthesized by a general method.10–13
Imide derivatives have numerous applications in bio-
logy, synthetic and polymer chemistry.1,2 Cyclic N-aryl-
imides have high antifungal activity, especially against
Sclerotinia sclerotiorum and Botrytis cinerea.3 However,
the availability of simple routes for their synthesis is
limited.
We herein report the synthesis of N-aryl-substituted
succinimides by decarboxylative oxidation of c-lactam
carboxylic acids. Many of the oxidants used for the decarb-
oxylation of carboxylic acids are metal derivatives, such as
lead(IV), cobalt(III), silver(II), manganese(III) and thal-
lium(III) salts; chromic acid and non-metallic oxidants
have also been reported.4
Cerium(IV) compounds, particularly ceric ammonium
nitrate [(NH4)2Ce(NO3)6, CAN], are notable oxidants. Cer-
ium(IV)-promoted oxidations were originally carried out
under strongly acidic conditions but recent studies have
focused on the development of much milder and more
convenient procedures with wider applications.5 Ho have
R1
R1
R2
R3
R2
CAN (1 equiv.)
NaBrO3 ( 2 equiv.)
R3
H
COOH
O
found that the dual oxidant system Ce4þ=BrO3 allows
ꢀ
N
N
Ph
H
CH3CN-H2O, Reflux
the use of cerium(IV) as a catalyst as it is continuously
O
O
Ph
1
2
*
Corresponding author. Tel.: +91 3222 283326; fax: +91 3222 282252.
Scheme 1. Decarboxylative oxidation of c-lactam-2-carboxylic acids.
E-mail address: jkray@chem.iitkgp.ernet.in (J. K. Ray).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.071

1406
G. Barman et al. / Tetrahedron Letters 49 (2008) 1405–1407
Table 1
In conclusion, we have developed a novel and simple
method for the decarboxylative oxidation of c-lactam-
carboxylic acids to N-arylsuccinimides in one step and in
good yields. This procedure demonstrates the potential of
the CAN–NaBrO3 reagent system as a decarboxylative oxi-
dating agent in refluxing acetonitrile–water as solvent. The
synthesis allows oxidation under mild conditions using low
cost reagents. The experimental simplicity of the reaction
opens new opportunities for the use of this reaction in syn-
thetic and industrial processes.
Synthesis of N-arylsuccinimides 2 from c-lactam-2-carboxylic acids 1a
Substrate N-aryl-c-lactam-2-
carboxylic acid
Product N-
arylsuccinimide
Yield
(%)
1a R1 = R3 = H, R2 = Cl
1b R1 = R3 = H, R2 = F
1c R1 = R3 = H, R2 = Br
1d R1 = R3 = H, R2 = CH3
1e R1 = R3 = R2 = H
1f R1 = Cl, R2 = F, R3 = H
a
Reagents and conditions: All the reactions were carried out with
1 equiv of CAN, and 2 equiv of NaBrO3 in CH3CN–H2O (1:1, v/v) at
80 °C for 5–8 h.
2a
2b
2c
2d
2e
2f
87
76
70
80
90
76
2. Typical experimental procedure
2.1. General procedure for the synthesis of 1,3-diaryl-
succinimides 2 from N-aryl c-lactam-2-carboxylic acid 1
Except for oxalic, malonic and a-hydroxycarboxylic
acids, carboxylic acids are resistant to oxidation with
cerium(IV). In our case CAN–NaBrO3 acts as a dual
oxidant although the cerium(IV) ion is the actual reagent.
Cerium(IV) has a high oxidation potential of +1.61 V
compared to the NHE (normal hydrogen electrode),14
and acts as a single electron oxidant. The oxidation by
To a flask containing the c-lactam-2-carboxylic acid 1
(1 mmol) in acetonitrile (10 mL) was added a mixture of
ceric ammonium nitrate (1 mmol) and NaBrO3 (2 mmol)
in water (15 mL) and the mixture was stirred for 15 min
at room temperature. The reaction mixture was refluxed
for 6–8 h (monitored by TLC) and then cooled to room
temperature. The solvent was evaporated under reduced
pressure and the residue was extracted with CH2Cl2. The
combined organic layer was washed successively with
H2O, 10% NaHCO3 solution and then again with more
H2O. After drying the organic layer with Na2SO4, the sol-
vent was evaporated under reduced pressure. The product
thus obtained was crystallized from an ethyl acetate–petro-
leum ether mixture.
ꢀ
CeðIVÞ=BrO3 occurred via a radical cation in the above
reaction. In 1974, Trahanovsky et al. proposed a mecha-
nism for the CAN mediated decarboxylative oxidation of
substituted phenyl acetic acids.4 However, the mechanism
of the reaction is uncertain, and we were unable to isolate
any intermediates, although a plausible mechanism may be
written as depicted in Scheme 2.15
The standard electrode potential, E0(CeIV/CeIII) is
unknown. The formal potential for equal concentrations
of cerium(IV) and cerium(III) varies considerably with the
nature and concentration of the acidic medium. Cerium-
3. Physical properties and spectral data of representative
compounds
ꢀ
(III) is converted to cerium(IV) bꢀy the BrO3 ion in the
reaction medium, also the BrO3 ion can oxidize the
alcohol formed during the course of the reaction.15 The
electronic configurations of CeIII and CeIV are [Xe]4f1
and [Xe]4f0 where Xe represents the xenon configuration.
The stability of the vacant f shell accounts for the ability
of cerium to exist in the CeIV oxidation state.14
3.1. Compound 2a, 1-(4-chlorophenyl)-3-phenylpyrrolidine-
2,5-dione
1
Light yellow solid; mp 158–162 °C, H NMR (CDCl3,
200 MHz) d 2.96 (dd, J = 4.9, 18.5 Hz, 1H), 3.32 (dd,
J = 4.5, 8.8 Hz, 1H), 4.16 (dd, J = 4.9, 9.6 Hz, 1H), 7.13–
7.54 (m, 9H). 13C NMR (CDCl3, 50 MHz) d: 36.96,
45.76, 127.24, 127.56, 127.98, 129.15, 129.21, 130.24,
134.26, 134.76, 174.75, 176.33, IR (CHCl3): mmax 1718,
O
Ce(IV)
ArCH2COOH
ArCH2
O
H
1685, 1560 cmꢀ1
,
ESI-MS for C16H12NO2Cl [M],
Ce(III)
[M+H+] = 286.071 (100%). HRMS (ESI) calcd for
C16H12NO2Cl [M+H+]: 286.063, found: 286.060.
Ce(IV)
.
ArCH2+CO2
+ H +
-
3.2. Compound 2b, 1-(4-fluorophenyl)-3-phenylpyrrolidine-
2,5-dione
BrO3
H +
Ce(IV)
1
Ar
H
Light yellow solid, mp 136–140 °C, H NMR (CDCl3,
+
+
O
Ce(III)
200 MHz) d 3.00 (dd, J = 4.9, 18.6 Hz, 1H), 3.38 (dd,
J = 9.5 Hz, 18.7 Hz, 1H), 4.19 (dd, J = 4.9, 9.5 Hz, 1H),
7.12–7.51 (m, 9H). 13C NMR (CDCl3, 50 MHz) d 37.12,
45.91, 115.98, 116.44, 127.33, 128.14, 128.20, 129.15,
129.31, 132.43, 136.93, 175.04, 176.5, IR (CHCl3): mmax
1717, 1655, 1509 cmꢀ1, ESI-MS for C16H12NO2F [M],
ArCH2
H2O
Ce(IV)
OH
ArCH2
Scheme 2. Mechanistic pathway.

G. Barman et al. / Tetrahedron Letters 49 (2008) 1405–1407
1407
[M+H+] = 270.088 (100%). HRMS (ESI) calcd for
C16H12NO2F [M+H+]: 270.085, found: 270.089.
127.30, 127.74, 128.23, 128.82, 129.04, 129.92, 136.62,
155.26, 160.26, 174.64, 176.20, IR (CHCl3): mmax 1718,
1654, 1500 cmꢀ1
, ESI-MS for C16H11NO2FCl [M],
[M+H+] = 304.055.
3.3. Compound 2c, 1-(4-bromophenyl)-3-phenylpyrrolidine-
2,5-dione
Acknowledgement
1
Light yellow solid, mp 155–158 °C, H NMR (CDCl3,
Financial support from DST and CSIR (New Delhi) is
gratefully acknowledged.
200 MHz) d 3.01 (dd, J = 4.9, 18.6 Hz, 1H), 3.39 (dd,
J = 9.6, 18.6 Hz, 1H), 4.20 (dd, J = 4.9, 9.6 Hz, 1H),
7.22–7.45 (m, 7H), 7.59–7.65 (m, 2H), 13C NMR (CDCl3,
50 MHz) d 37.07, 45.87, 122.45, 127.30, 127.87, 128.10,
129.79, 130.81, 133.75, 136.78, 174.69, 176.25, IR (CHCl3):
mmax 1718, 1655, 1508 cmꢀ1, ESI-MS for C16H12NO2Br
[M], [M+H+] = 330.020 (79Br), 332.020 (81Br).
References and notes
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Yellow viscous dense liquid 1H NMR (CDCl3,
200 MHz) d: 3.00 (dd, J = 4.9, 18.7 Hz, 1H), 3.35 (dd,
J = 9.6, 18.6 Hz, 1H), 4.20 (dd, J = 4.8, 9.5 Hz, 1H),
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45.87, 116.75, 117.20, 121.53, 121.90, 126.29, 126.43,
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