Conversion of N-Acyl amino acids into imides via oxidative decarboxylation induced by Ag+/Cu2+/S2O8 2- in water

Article abstract of DOI:10.1055/s-2008-1072563

N-Acyl amino acids can be converted by oxidative decarboxylation induced by Ag⁺/Cu²⁺/S₂O₈^2- at room temperature in water into imides in 24-89% yields. Both N-benzoylvaline and N-benzoylleucine gave N-

Full text of DOI:10.1055/s-2008-1072563

1342
SHORT PAPER
Conversion of N-Acyl Amino Acids into Imides via Oxidative Decarboxylation
2–
Induced by Ag+/Cu2+/S2O8 in Water
Conversionof
N-Acyl
A
e
mino Acid
n
s
into Imide
s
hua Huang,* Meiling Wang, Hong Yue
Department of Chemistry, Tianjin University, Tianjin 300072, P. R. of China
Fax +86(22)27403475; E-mail: huangwh@tju.edu.cn
Received 25 December 2007; revised 15 January 2008
Oxidative decarboxylation of N-acyl amino acids 1 with
Abstract: N-Acyl amino acids can be converted by oxidative decar-
boxylation induced by Ag+/Cu2+/S2O82– at room temperature in wa-
ter into imides in 24–89% yields. Both N-benzoylvaline and N-
benzoylleucine gave N-formylbenzamide, which possibly results
from oxidative cleavage of an enamide intermediate.
stoichiometric persulfate and catalytic silver(I) (Ag+/
S2O82–) can form the 1-amidoalkyl radical 2, which has
been applied in the Minisci reaction.6 The radical 2 is eas-
ily oxidized to iminium species 3, which gives amide 6
and an aldehyde probably via carbinolamide 4 after hy-
drolysis (Scheme 1, path B).6c Our initial work7 demon-
strated that oxidative decarboxylation of N-aroylglycine
Key words: oxidative decarboxylation, silver, copper, imide,
amino acid
2–
(Scheme 1, R2 = R3 = H) using Ag+/S2O8 at 60 °C in a
two-phase system (H2O–CHCl3) could produce imide 5
via an alternative pathway that included oxidation of
carbinolamide 4 (path A). However, attempts to extend
this reaction to other amino acids failed, for example, N-
benzoylalanine gave benzamide in 82% yield still via path
B. This has driven us to explore this reaction further. After
numerous trials, we found that imide 5 could be obtained
by increasing the amount of silver(I) and introducing cop-
per(II) as a co-catalyst at room temperature. The results
are summarized in Table 1.
Oxidative decarboxylation of amino acids not only has
been widely applied in organic synthesis1 but it also has
implications in biological activity.2 Several methods have
been reported for the conversion of N-acyl amino acids to
imides via oxidative decarboxylation using various oxi-
dants, such as lead tetraacetate,3a iodosobenzene,3b molec-
ular oxygen,4a and m-chloroperbenzoic acid.4b However,
these methods either use stoichiometric amounts of heavy
metals, or use expensive reagents, or require an additional
step. Recently, Masaki5 et al. reported that N-acyl amino
acids can be converted into imides via oxidative photode-
carboxylation in the presence of a mesoporous silica, but
organic solvents and long reaction times were required.
Herein we report a simple method for conversion of N-
acyl amino acids into imides via oxidative decarboxyla-
tion by using persulfate as an oxidant, silver(I) and cop-
per(II) as catalysts (Ag+/Cu2+/S2O82–), and water as
solvent.
As can be seen from Table 1, compound 5b was obtained
in 84% isolated yield when 1b was treated with three
equivalents of ammonium persulfate in the presence of
silver nitrate (20 mol%) and copper(II) sulfate (20 mol%)
using water as the solvent. This result is in sharp contrast
to our previous result, indicating that path B was almost
completely suppressed under these reaction conditions.
The yield of 5a from hippuric acid (1a) was slightly lower
(77%), but higher than that in our initial work (71%).7a N-
Benzoyl-a-phenylglycine (1c) gave 5c in 79% yield, but
the replacement of benzoyl with acetyl drastically reduced
the yield of 5b to 32%. For 1c, the resonance of the PhCO
moiety reduces the resonance effect of the amide bond,
which results in an increase in the stability of 4 and, there-
fore, favors path A. On the other hand, for 1d, the strong
resonance of the amide bond may accelerate the hydroly-
sis of 4 (path B).7b Compound 1e, which is a secondary
amide and readily prepared8 from the condensation of
phthalaldehyde with alanine, gave 5e in the highest yield
(89%).
R2
O
O
R2
O
2–
Ag+/S2O8
+
R1
N
R3
COOH
R1
N
R3
5
O
R1
NH
R3
1
6
+
Ag2
2–
– H+
S2O8
oxidation
path A
– R2CHO
path B
– CO2
–
2–
Ag+
R2
•
SO4
SO
R1
+
4
O
O
R2
O
R2
hydrolysis
oxidation
R1
N
R3
N
R3
R1
N
OH
–
•
2–
SO4
SO4
R3
2
3
4
In the case of N-benzoylproline (1f), however, compound
5f was obtained in only 24% yield. Surprisingly, for N-
benzoylvaline (1g), the product was not the expected N-
isobutyrylbenzamide but 5a (85%) identified by compar-
ison to the product from 1a by 1H NMR, TLC, and IR. N-
Benzoylleucine (1h) also gave 5a but in a lower yield
(60%) upon using four equivalents of persulfate. The re-
action seemed to proceed via enamide 7, which formed
Scheme 1
SYNTHESIS 2008, No. 9, pp 1342–1344
Advanced online publication: 27.03.2008
DOI: 10.1055/s-2008-1072563; Art ID: F23807SS
x
x
.
x
x
.2
0
0
8
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Conversion of N-Acyl Amino Acids into Imides
1343
Table 1 Conversion of N-Acyl Amino Acids into Imidesa
R4
R5
O
R4
R5
Ag+/Cu2+/S2O8
2–
+
5a
Ph
N
H
COOH
5
1
O
H2O, r.t.
8
1b,g,h
Entry Substrate 1
Product 5
Yield
(%)
oxidative
decarboxylation
oxidative path C
cleavage
O
O
O
O
O
O
H
R4
O
R5
R4
R5
1
2
3
4
1a
1b
1c
1d
5a
77
84
79
32
O
tautomerization
Ph
Ph
Ph
N
H
COOH
COOH
COOH
N
H
Ph
O
O
O
Ph
N
H
Ph
N
H
5b
3b,g,h
7b,g,h
N
H
Ph
N
H
Scheme 2 Proposed mechanism for the formation of 5a from 1g,h
Ph
Ph
5c
amino acids, the imides could be formed in two ways: one
is oxidation of a carbinolamide intermediate without
touching the side chain for glycine, alanine, or a-phenyl-
glycine; another is oxidative cleavage of a possible en-
amide intermediate with loss of the side chain for valine
or leucine to give an N-formylimide. This methodology
may find applications in peptide modification.
N
H
Ph
N
H
O
Ph
O
Ph
5b
5e
N
COOH
N
O
H
H
N
N
5
1e
89
COOH
O
O
O
Compounds 1b–h were prepared according to the literature proce-
dure.8,10 All the products were confirmed by comparison to known
compounds (IR, NMR, and TLC).7,11 1H NMR spectra were record-
ed on a MercuPlus 400 NMR spectrometer. IR spectra were record-
ed on a Thermo Nicolet Avatar 360 IR spectrophotometer. All
melting points were measured on a melting point apparatus with mi-
croscope and hot stage and were uncorrected. All reactions were
carried out under N2. PE = petroleum ether (bp 60–90 °C). Hippuric
acid (1a) was purchased from GuangFu Chemical Reagent Com-
pany, China. (NH4)2S2O8, CuSO4·5H2O, and silver nitrate were pur-
chased from Kewei Chemical Reagent Company, China. These
chemicals were used directly as received. The deionized water, pur-
chased from Water Center of Nankai University, China, was dis-
tilled before use.
O
O
COOH
O
6
7
1f
5f
24
85
Ph
Ph
N
Ph
Ph
N
O
O
O
O
1g
5a
N
H
O
O
N
H
COOH
8
1h
5a
60b
Ph
N
H
Ph
N
H
COOH
a Reaction conditions: persulfate (3 equiv), AgNO3 (0.2 equiv),
CuSO4·5 H2O (0.2 equiv).
N-Acetylbenzamide (5b); Typical Procedure
To a round-bottom flask (50 mL), 1b (77.3 mg, 0.4 mmol), AgNO3
(13.5 mg, 0.08 mmol), CuSO4·5 H2O (20.0 mg, 0.08 mmol), and
(NH4)2S2O8 (273.8 mg, 1.2 mmol) were added. The flask was cov-
ered with a septum and protected under N2, deionized H2O (5 mL)
was added by syringe after it had been degassed by sparging with
b Used 4 equiv of persulfate.
from imines 3g,h through tautomerization and gave 5a af-
ter oxidative cleavage (Scheme 2, path C). Needles and
Ivanetich9 isolated N-(2-methylpropenyl)acetamide in the N2. The mixture was stirred at r.t. for 1 h and EtOAc (10 mL) was
added and the mixture was filtered. The EtOAc phase was separated
from the filtrate and the aqueous phase was extracted with EtOAc
(2 × 10 mL). The combined extracts were dried (anhyd Na2SO4),
concentrated under reduced pressure, and separated by preparative
oxidative decarboxylation of N-acetylvaline with lead tet-
raacetate in N,N-dimethylformamide. The ease of the for-
mation of enamide 7 increases with substitution on the
carbon–carbon double bond. Therefore, 7b would be too
TLC (PE–EtOAc, 2:1). N-Acetylbenzamide (5b) was obtained from
unstable to form so that 5b was obtained in high yield still
via path A (Scheme 1). Enamide 7g has one more substit-
uent than 7h, and therefore forms more readily, which
may account for a higher yield of 5a from 1g than that
from 1h.
1b or 1d in 84% or 32% yields, respectively, as a white solid; mp
109–110 °C (Lit.11a 115 °C).
IR (KBr): 1738, 1679 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.30 (s, 3 H, CH3), 7.44–7.49
(m, 2 H, 3,5-Ar-H), 7.55–7.58 (m, 1 H, 4-Ar-H), 7.85–7.88 (m, 2 H,
2,6-Ar-H), 10.98 (br s, 1 H, NH).
In summary, we have demonstrated that N-acyl amino ac-
ids can be converted into imides via oxidative decarboxy-
lation induced by Ag+/Cu2+/S2O82–. The reaction was
performed at room temperature using catalytic amounts of
metals, an inexpensive oxidant, and water as the solvent,
hence it provides a simple method to access imides start-
ing from amino acids. Depending on the structure of the
N-Formylbenzamide (5a)
Obtained from 1a, 1g, or 1h (using 4 equiv of persulfate for 1h) in
77%, 85%, or 60% yields, respectively, as a white solid, preparative
TLC (PE–EtOAc, 3:1); mp 109–110 °C (Lit.3 109–110 °C).
IR (KBr): 1724, 1670 cm–1.
Synthesis 2008, No. 9, 1342–1344 © Thieme Stuttgart · New York

1344
W. Huang et al.
SHORT PAPER
1H NMR (400 MHz, DMSO-d6): d = 7.50–7.55 (m, 2 H, 3,5-Ar-H),
7.62–7.65 (m, 1 H, 4-Ar-H), 7.98–8.01 (m, 2 H, 2,6-Ar-H), 9.23 (d,
J = 8.0 Hz, 1 H, CHO), 11.72 (br s, 1 H, NH);
(2) Majer, F.; Schmid, D. G.; Altena, K.; Bierbaum, G.; Kupke,
T. J. Bacteriol. 2002, 184, 1234.
(3) (a) Gledhill, A. P.; McCall, C. J.; Threadgill, M. D. J. Org.
Chem. 1986, 51, 3196. (b) Ochiai, M.; Inenaga, M.; Nagao,
Y.; Moriarty, R. M.; Vaid, R. K.; Duncan, M. P. Tetrahedron
Lett. 1988, 29, 6917.
(4) (a) Suda, K.; Hino, F.; Yijima, C. Chem. Pharm. Bull. 1985,
33, 882. (b) Lucente, G.; Pinnen, F.; Sanotti, G. Tetrahedron
Lett. 1978, 19, 3155.
(5) (a) Itoh, A.; Kodama, T.; Inagaki, S.; Masaki, Y. Chem. Lett.
2000, 542. (b) Itoh, A.; Kodama, T.; Masaki, Y.; Inagaki, S.
Chem. Pharm. Bull. 2006, 54, 1571.
N-Benzoylbenzamide (5c)
Obtained from 1c in 79% yield as white needles, preparative TLC
(CH2Cl2–MeOH, 50:1); mp 144–145 °C (Lit.12a 144–145 °C).
IR (KBr): 1704 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 7.47–7.52 (m, 4 H, 3,5-Ar-H),
7.58–7.61 (m, 2 H, 4-Ar-H), 7.87–7.89 (m, 4 H, 2,6-Ar-H), 11.31
(br s, 1 H, NH);
(6) (a) Minisci, F.; Vismara, E.; Fontana, F. Heterocycles 1989,
28, 489. (b) Tada, M.; Furuse, R.; Kashima, H. Heterocycles
1992, 34, 357. (c) Cowden, C. J. Org. Lett. 2003, 5, 4497.
(7) (a) Huang, W.; Zhang, L. J. Chem. Res., Synop. 2006, 738.
(b) We thank a reviewer for suggesting this explanation.
(8) Grigg, R.; Gunaratne, H. Q. N.; Sridharan, V. Chem.
Commun. 1985, 1183.
2-Acetyl-2,3-dihydro-1H-isoindol-1-one (5e)
Obtained from 1e in 89% yield as short white needles, preparative
TLC (CH2Cl2–MeOH, 50:1); mp 120–121 °C.
IR (KBr): 1720, 1686 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 2.51 (s, 3 H, CH3), 4.75 (s, 2
H, CH2), 7.51–7.56 (m, 1 H, 3-Ar-H), 7.62–7.65 (m, 1 H, Ar-5-H),
7.70–7.75 (m, 1 H, 4-Ar-H), 7.79–7.82 (m, 1 H, 2-Ar-H).
(9) Needles, H. L.; Ivanetich, K. Chem. Ind. (London) 1967,
581.
(10) (a) Holland, H. L.; Andreana, P. R.; Salehzadeh-Asl, R.;
van Vilet, A.; Ihasz, N. J.; Brown, F. M. Monatsh. Chem.
2000, 131, 667. (b) Leone-Bay, A.; Santiago, N.; Achan, D.;
Chaudhary, K.; DeMorin, F.; Falzarano, L.; Haas, S.;
Kalbag, S.; Kaplan, D.; Leipold, H.; Lercara, C.; O’Toole,
D.; Rivera, T.; Rosado, C.; Sarubbi, D.; Vuocolo, E.; Wang,
N.; Milstein, S.; Baughman, R. A. J. Med. Chem. 1995, 38,
4263. (c) Youshko, M. I.; van Langen, L. M.; Sheldon, R.
A.; Svedas, V. K. Tetrahedron: Asymmetry 2004, 15, 1933.
(d) Barton, D. H. R.; Ferreira, J. A. Tetrahedron 1996, 52,
9367.
1-Benzoylpyrrolidin-2-one (5f)
Obtained from 1f in 24% yield as a white solid, preparative TLC
(PE–EtOAc, 3:1); mp 87–88 °C (Lit.12b 89–90 °C)
IR (KBr): 1743, 1664 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 1.95–2.03 (m, 2 H,
CH2CH2N), 2.48 (t, J = 8.0 Hz, 2 H, COCH2), 3.76 (t, J = 7.2 Hz, 2
H, CH2CH2N), 7.35–7.39 (m, 2 H, 3,5-Ar-H), 7.45–7.52 (m, 3 H,
2,4,6-Ar-H).
(11) (a) Moffatt, J. G.; Lerch, U. J. Org. Chem. 1971, 36, 3391.
(b) Morris, J. M.; Dunmire, R. B.; Newkome, G. R.; Koenig,
P. E. J. Org. Chem. 1972, 37, 1244. (c) Gramain, J. C.;
Simonet, N.; Vermeersch, G.; Febvay-Garot, N.; Caplain,
S.; Lablache-Combier, A. Tetrahedron 1982, 38, 539.
(d) Giovannini, A.; Savoia, D.; Umani-Ronchi, A. J. Org.
Chem. 1989, 54, 228.
Acknowledgment
We thank Tianjin University for providing a starting research fund
for W.H.
References
(12) (a) Etter, M. C.; Reutzel, S. M. J. Am. Chem. Soc. 1991, 113,
2586. (b) Sasaki, H.; Mori, Y.; Nakamura, J.; Shibasaki, J.
J. Med. Chem. 1991, 34, 628.
(1) Boto, A.; Hernandez, R.; de Leon, Y.; Suarez, E. J. Org.
Chem. 2001, 66, 7796; and references therein.
Synthesis 2008, No. 9, 1342–1344 © Thieme Stuttgart · New York