Reactions of N-acetyl- and N-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with meta-cloroperbenzoic acid

Article abstract of DOI:10.1134/S1070363208080161

Reaction of N-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with meta-cloroperbenzoic acid leads to the corresponding 2-[1-o-(3-chlorobenzoyl)-2- hydroxycyclopent-1-yl]anilines. 5-(2-Acetylaminophenyl)-5-oxopentanic or 6-oxohexanic acids are formed as main

Full text of DOI:10.1134/S1070363208080161

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 8, pp. 1565–1568. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.Kh. Fattakhov, I.B. Abdrakhmanov, R.R. Gataullin, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 8, pp. 1330–
1333.
Reactions of N-Acetyl- and N-Ethoxycarbonyl-2-(1-cycloalken-1-
yl)anilines with meta-Cloroperbenzoic Acid
A. Kh. Fattakhov, I. B. Abdrakhmanov, and R. R. Gataullin
Institute of Organic Chemistry, Ufa Scientific Centre, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Russia
e-mail: al_fatt@mail.ru
Received February 4, 2008
Abstract—Reaction of N-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with meta-cloroperbenzoic acid leads
to the corresponding 2-[1-o-(3-chlorobenzoyl)-2-hydroxycyclopent-1-yl]anilines. 5-(2-Acetylaminophenyl)-5-
oxopentanic or 6-oxohexanic acids are formed as main products in the reaction of N-acetyl-2-(1-cycloalken-1-
yl)anilines with m-chloroperbenzoic acid in CH2Cl2. N-Acetyl-2-(1-cyclopenten-1-yl)-3,6-dimethylaniline is an
exception in this series since its reaction stops at the stage of epoxide formation.
DOI: 10.1134/S1070363208080161
Aniline 2-cycloalkenyl derivatives are used in the
synthesis of natural compounds [1], show good
inhibiting properties of steel in aggressive media [2]
and possess local anesthetic activity like well-known
anesthetics [3, 4].
Protective group at the nitrogen atom affects the
structure of the reaction products. A mixture of
benzoxazine IVa–IVd and ketoacid Va–Vd, where the
latter was the main reaction product was obtained from
N-acetyl derivatives IIIa–IIIc under analogous
conditions. In the reaction mixture ester VIb was
found in the case of anilide IIIb. Formation of
compounds IV–VI we ascribe to further transforma-
tions of intermediate epoxide A. The intramolecular
cyclization of the epoxide gave benzoxazines IVa-
IVd, and the reaction with m-chloroperbenzoic acid
furnished ester VIb. The known intramolecular
rearrangements of epoxide B [5,6] gave rise to ketone
B, which underwent subsequent oxidation into
ketoacid Va–Vd (Scheme 2).
In this report we outline results of our investigation
of the reaction of 2-(1-cycloalken-1-yl)anilines with m-
chloroperbenzoic acid.
Reactions of N-ethoxycarbonyl-2-(1-cycloalken-1-
yl)anilines Iа, Ib with m-chloroperbenzoic acid afford
esters IIа, IIb in high yields. It is evident that the
esters are the products of secondary reaction of inter-
mediate epoxide cleavage according to A.K.
Krasusky’s rule (Scheme 1). Epoxide А was not found
in the reaction mixture.
Scheme 1.
Cl
O
O
Cl
O
OOH
OH
R
R
O
R
m-CPBA
CH2Cl2
0oC
NHCOC2H5
O
NHCOC2H5
O
NHCOC2H5
O
Iа, Ib
А
IIа, IIb
R = H (а), Me (b).
1565

1566
FATTAKHOV et al.
Scheme 2.
O
(CH2)n
(CH2)n
O
(CH2)n
R1
R1
R1
m-CPBA
CH2Cl2
0oC
NHCCH3
O
NHCCH3
O
NHCCH3
O
R
R
R
C
IIIа−IIId
B
[O]
Cl
O
(CH2)n
HO
(CH2)n
OH
O
O
O
R1
R1
(CH2)n
R1
OH
O
NHCCH3
N
CH3
NHCCH3
O
R
R
R
O
IVа−IVd
VIb
Vа−Vd
n = 1: R = R' = H (a); R = H, R' = Me (b); R = Me, R' = H (c); n = 2: R = H, R' = Me (d).
Ketoacid did not pass into the aqueous solution and
did not form potassium or sodium salts at the treatment
with aqueous solution of sodium carbonate or
hydrogen carbonate evidently due to the
transformation of the linear form L into the cyclic
form C in alkaline medium. The equilibrium is
displaced to the linear form in neutral solutions
(Scheme 3).
Scheme 3.
O
O
O
O
OH
(CH2)n
R
R
(CH2)n
OH− (pH > 7)
pH 7.0
OH
NHAc
NHAc
C
L
We observed in deutrochloroform only signals of
the epoxidized cyclopentane ring that is not favorable
for intramolecular SN2-attack (Scheme 4).
ketoacid L since a base was absent.
Reaction of N-acetyl derivative IIIe with m-
chloroperbenzoic acid stopped at the stage of epoxide
VII formation. In this case obviously the presence of
methyl group at C3-position of aromatic ring created
certain steric hindrances for the formation of esters of
type VIa or benzoxazine structure of type IVa–IVd.
The absence of the latter in the reaction mixture is
caused evidently by a hindered spatial arrangement of
The presence of the methyl substituent provided
evidently a stabilizing effect on the epoxy group
therefore rearrangement into ketone of type B, the
ketoacid precursor, did not occur. Spectral analysis of
compounds II showed that in H1 NMR spectrum of II
all proton signals of aromatic rings are sufficiently
resolved and correspond to calculated values. In the
aromatic region of the spectrum except for vicinal
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 8 2008

REACTIONS OF N-ACETYL- AND N-ETHOXYCARBONYL-2-(1-CYCLOALKEN-1-YL)ANILINES
1567
Scheme 4.
N-Ethoxycarbonyl-2-[1-O-(3-chlorobenzoyl)-2-
hydroxycyclopent-1-yl]aniline (IIа). A viscous trans-
parent substance; yield 0.4 g (50%), Rf 0.3 (CНCl3). 1Н
NMR spectrum, CDCl3, δ, ppm: 1.32 d. t (3Н, CН3, J1
0.5, J2 7.1 Hz), 1.40–2.55 m (6Н, 3CН2), 2.72 b. s (1Н,
OН), 4.21 d. q (2Н, CН2, J1 0.8, J2 7.1 Hz), 5.95 t (1H,
H2, J 7.3 Hz), 6.99 d. t (1H, ArH, J1 0.5, J2 7.4 Hz),
7.12 d. d (1H, ArH, J11.2, J2 7.9 Hz), 7.35–7.42 m
(2H, ArH), 7.56 d. d. d (1H, ArH, J1 1.1, J2 2.1, J3
7.9 Hz), 7.89 d. d. d (1H, ArH, J1 1.0, J2 1.5, J3 7.9 Hz),
7.98 d. d (1H, ArH, J1 1.0, J2 1.8 Hz), 8.08 d (1H,
ArH, J 8.0 Hz), 8.78 b. s (1H, NH). Found, %: C
62.35; Н 5.25; Cl 8.86; N 3.52. C21H22ClNO5.
Calculated, %: C 62.46; Н 5.49; Cl 8.78; N 3.47.
CH3
CH3
O
m-CPBA
CH2Cl2
0oC
NHAc
NHAc
CH3
CH3
IIIe
VII
constants (7–8 Hz), a majority of signals have spin-
spin coupling constants (0.5–1.5 Hz) owing to the
presence of chlorine atom in the molecule. The signal
of Н2' proton of cyclopentane ring is a triplet with spin-
spin coupling constant of 7.3 Hz, showing that dihedral
angles with both Н3a and Н3b protons of methylene
group C3Н2 are approximately equal. Signals of
protons from NH and OH groups are observed at δ
8.78 ppm and 2.72 ppm respectively. The ethoxy
group gives rise to a triplet signal of CН3 group and a
quadruplet two-proton signal of CН2 group.
N-Ethoxycarbonyl-2-[1-O-(3-chlorobenzoyl)-2-
hydroxy(cyclopent-1-yl)]-4-methylanili-ne (IIb). A
viscous transparent substance; yield 0.4 g (48%); Rf
0.3 (CНCl3). 1Н NMR spectrum, CDCl3, δ, ppm: 1.30 t
(3Н, CН3, J 7.1 Hz), 1.41–2.54 m (6Н, 3CН2), 2.11 s
(3Н, CН3), 2.77 b. s (1Н, OН), 4.20 q (2Н, CН2, J
7.1 Hz), 5.90 t (1Н, Н2, J 7.3 Hz), 6.68 d (1Н, ArН, J
7.2 Hz), 6.72 s (1Н, ArН), 6.89 d (1Н, ArН, J 7.2 Hz),
7.37 m (1Н, ArН), 7.52 d. d. d (1Н, ArН, J1 1.0, J2 2.0,
J3 7.8 Hz), 7.88 d. d. d (1Н, ArН, J1 1.0, J2 1.5, J3
7.8 Hz), 8.00 d. d (1Н, ArН, J1 1.0, J2 1.7 Hz), 8.80 b.
s (1Н, NН). Found, %: C 64.46; Н 5.89; Cl 8.72; N
3.28. C21H24ClNO5 Calculated, %: C 63.23; Н 5.79; Cl
8.48; N 3.35.
Composition and structure of the other compounds
obtained are also proved by elemental analysis and
spectral methods. Characteristics of compounds Iа–Ic
and Vа–Vc correspond to the described ones.
EXPERIMENTAL
The Н and 13C NMR spectra were recorded on a
1
Bruker AM-300 spectrometer at operating frequencies
of 300.13 and 75.45 MHz, internal reference TMS.
Elemental analysis was performed on an Analyzer М-
185В. Column chromatography was carried out on a
silica gel 40/70 µm (Lancaster). For TLC qualitative
analysis silufol plates Sorbfil (Sorbpolymer,
Stavropol’) were used, detection by UV-irradiation (λ
254 nm) and iodine vapor. The mass spectra were
obtained on a spectrometer МKh 1320 (70 eV).
2'-Hydroxy-2-methylspiro[4Н-benz-1-оxazine-
6,1'-cyclopentane] (IVа). Yield 0.039 g (9%). Physico-
chemical constants correspond to [7].
2'-Hydroxy-2,6-dimethylspiro[4Н-benz-1-оxazine-
6,1'-cyclopentane] (IVb). Yield 0.05 g (11%). Physico-
chemical constants correspond to [8].
2'-Hydroxy-2,8-dimethylspiro[4Н-benz-1-оxazine-
6,1'-cyclopentane] (IVc). Yield 0.037 g (8%). Physico-
chemical constants correspond to [7].
Oxidation of N-acetyl- and N-ethoxycabonyl-2-
(1-cycloalken-1-yl)anilines Ia and Ib, IIIa–IIIe with
m-chloroperbenzoic acid. To a solution of 2 mmol of
anilide Ia, Ib or IIIa–IIIe in 10 ml of CH2Cl2 was
added 0.69 g of m-chloroperbenzoic acid in 10 ml of
CH2Cl2, and then 0.1 g of K2CO3. The reaction mixture
was stirred at room temperature. The reaction progress
was followed by TLC, eluent benzene. Then the
reaction mixture was treated by a saturated solution of
NaHCO3 (2×10 ml) and water (2×10 ml). The reaction
products were isolated by column chromatography on
silica gel, elution with benzene and benzene–ethyl
acetate mixture (ratio from 9:1 to 1:1).
We failed to isolate compound IVd in pure form.
5-(2-Acetamidophenyl)-5-oxopentanic acid (Va).
Yield 0.3 g (61%). Physicochemical constants cor-
respond to [10].
5-(2-Аcetamido-5-methylphenyl)-5-оxopentanic
acid (Vb). Yield: 0.247 g (47%). An amorphous
powder; yield 0.247 g (47%); Rf 0.3 (benzene). Н
NMR spectrum, CDCl3, δ, ppm: 2.10 t (2Н, CН2, J
7.1 Hz), 2.14 s, 2.25 s (3Н, 2CН3), 2.52 d. t (2Н, CН2,
J1 1.0, J2 7.1 Hz), 3.02 t (2Н, CН2, J 7.1 Hz), 6.95 d
(1Н, ArН, J 8.6 Hz), 7.60 s (1H, ArН), 8.50 d (1H, H,
1
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1568
FATTAKHOV et al.
J 8.6 Hz), 9.75 s (1H, NH), 11.45 s (1Н, COOН).
Found, %: C 63.63; H 6.39; N 5.21. C14H17NO4.
Calculated, %: C 63.87; H 6.51; N 5.32.
7.8 Hz), 7.64 b. s (1H, NH). Маss-spectrum, m/e: 246
[MH]+, 244 [M – H]–. Found, %: C 73.21; Н 7.59; N
5.47. C15H19NO2. Calculated, %: C 73.44; Н 7.81; N
5.71.
5-(2-Аcetamido-3-methylphenyl)-5-oxopentanic
acid (Vc). Yield 0.33 g (63%); Rf 0.2 (CНCl3–МеOН
4 : 1). Physicochemical constants correspond to [9].
REFERENCES
1. Danishefsky, S. and Philips, G.B., Tetrahedron Lett.,
1984, vol. 25, p. 3159.
5-(2-Аcetamido-3-methylphenyl)-6-oxohexanic
acid (Vd). A viscous transparent substance; yield 0.2 g
(35%); Rf 0.3 (benzene). 1Н NMR spectrum, CDCl3, δ,
ppm: 1.40-1.19 m (4Н, 2CН2), 2.15 s, 2.20 s (3Н,
2CН3), 2.55 t (2Н, CН2 J 6.6 Hz), 3.03 t (2Н, CН2, J
6.6 Hz), 7.20 t (1H, ArH, J 7.5 Hz), 7.45 d (1H, ArH, J
7.5 Hz), 7.60 d (1H, ArH, 7.5 Hz), 9.25 b. s (1H, NH),
9.80 s (1Н, COOН). Found, %: C 63.89; H 6.35; N
5.27. C15H19NO4. Calculated, %: C 64.11; H 6.15; N
5.34.
2. Gataullin, R.R., Kazhanova, Т.V., Khaziyev, E.V., Bo-
risov, I.M., and Abdrakhmanov, I.B., Zh. Prikl. Khim.,
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Chem. Soc., 1950, vol. 72, p. 1997.
N-Аcetyl-2-[1-O-(3-chlorobenzoyl)-2-hydroxy-
cyclopent-1-yl]-4-methylaniline (VIb). A viscous
transparent substance; yield 0.15 g (19%); Rf 0.3
1
(CНCl3). Н NMR spectrum, CDCl3, δ, ppm: 1.45–
2.52 m (6Н, 3CН2), 1.93 s (3Н, CН3), 2.70 b. s (1Н,
OН), 5.93 t (1Н, Н2', J 7.2 Hz), 6.79 d (1Н, ArН, J
7.5 Hz), 6.83 s (1Н, ArН), 7.43 m (1Н, ArН), 7.54 d.
d.d (1Н, ArН, J1 1.0, J2 2.0, J3 7.7 Hz), 7.83 d.d.d (1Н,
ArН, J1 1.0, J2 1.3, J3 7.9 Hz), 8.06 d. d (1Н, ArН, J1
1.0, J2 1.6 Hz), 8.60 b. s (1Н, NН). Found, %: C 63.57,
Н 5.25; Cl 8.25; N 3.30. C21H21ClNO4. Calculated, %:
C 62.46; Н 5.49; Cl 8.78; N 3.47.
8. Gataullin, R.R., Nasyrov, M.F., Shitikova, O.V.,
Spirikhin, L.V., and Abdrakhmanov, I.B., Mendeleev
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Kabal’nova, N.N., and Abdrakhmanov, I.V., Zh. Org.
Khim., 2002, vol. 38, no. 5, p. 799.
N-Acetyl-2-(1,2-epoxycyclopent-1-yl)-3,6-dime-
thylaniline (VII). A viscous transparent substance;
yield 0.2 g (41%); Rf 0.5 (benzene). 1Н NMR
spectrum, CDCl3, δ, ppm: 1.42–2.39 m (6Н, 3CН2),
2.14 s, 2.16 s, 2.19 s (3Н, 3CН3), 3.53 s (1Н, Н2`),
6.91 d (1Н, ArН, J 7.8 Hz), 7.05 d (1H, ArН, J
10. Gataullin, R.R., Nasyrov, M.F., D’yachenko, D.I.,
Fatykhov, A.A., Shytikova, O.V., Spirikhin, L.V., and
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