4042
A. Arcelli et al. / Tetrahedron 57 (2001) 4039±4043
i
ii
O
N
HN
HN
HO
90%
65%
O
N
O
N
O
Ph
Ph
Ph
O
OCOPh
PhCOO
4
3
Scheme 4. )i) PhCOCl and TEA in CHCl3 50 h at re¯ux; )ii) Na2CO3.H2O in H2O/acetone 2 h at rt.
3. Conclusions
and TEA )1.4 mL, 10 mmol) was added. Then, benzoyl
chloride )1.5mL, 13 mmol) dissolved in 5mL of CHCl
3
In this paper we have described the acid hydrolysis
of substrate 1 and ascertained the unusual mechanism
involving the loss of the assisting vicinal amide group. A
reasonable explanation of the different behaviour towards
the acid hydrolysis between the substrates 1 and 5,
previously investigated,1,3 could be based on the different
basicity of the leaving group during the opening of the
cyclic intermediate. In fact, in substrate 1 the leaving
group is better than in 5 owing to a lower basicity arising
from the overlap of the phenyl ring and the lone pair on the
nitrogen. The o-alkyl substituents in 5 strongly reduce the
conjugation of the nitrogen lone pair with the phenyl ring
and increase the basicity, as reported for N-alkyl substituted
anilines.10
was dropped into the stirring solution and the reaction
mixture was re¯uxed for 3 h. After evaporation of the
solvent, the residue was acidi®ed with diluted HCl and
extracted with ethyl acetate. Evaporation to dryness in
vacuo gave the crude reaction product that, after silica gel
chromatographic puri®cation eluting with hexane/ethyl-
acetate, was recovered pure as an oil in 80% yield.
n
max)neat)1659, 1606, 1493, 1347, 1109, 698 cm21; dH
1.18 )3H, d, J7, CHCH3), 3.39 )3H, s, OCH3), 3.41 )3H,
m, OCH2CH), 7.06±7.29 )10H, m, Ph); dC 15.6, 51.5, 58.5,
73.6, 127.2, 127.4, 128, 128.5, 128.8, 130.3, 137, 139.6,
171; [Found: C, 75.84; H, 7.1. C17H19NO2 requires: C,
75.81; H, 7.11%].
4.1.2. 2-)N-phenylamino)propylbenzoate )3). It was
synthesized by following the procedure summarized in
Scheme 4. Benzoyl chloride )7 mL, 60 mmol) in CHCl3
)10 mL) was dropped into a solution of 2-)N-phenylamino)
propanol )4) )3 g, 20 mmol) and TEA )5.6 mL, 40 mmol) in
CHCl3 )20 mL). The reaction mixture was re¯uxed for
about 50 h. After evaporation of the solvent, the residue
was dissolved in ethyl acetate and washed with diluted
HCl. The organic solvent was evaporated and the pure
dibenzoyl derivative was isolated in 90% yield after silica
gel chromatography eluting with hexane/ethyl acetate [dH
1.32 )3H, d, J7, CHCH3), 4.42 )2H, m, CH2O), 5.4 )1H, m,
CHCH3), 7.15)10H, m, Ph), 7.5)3H, m, Ph), 8.05)2H, m,
Ph)]. The intermediate product )3.6 g, 10 mmol) was
dissolved in acetone )60 mL) and Na2CO3.H2O )1.24 g,
10 mmol) in water )30 mL) was added. The reaction
mixture was stirred at rt and monitored by TLC. After
about 2 h the acetone was evaporated in vacuo and the
residue was extracted with ethyl acetate. The organic
solvent was evaporated and the residue submitted to silica
gel chromatographic puri®cation eluting with hexane/ethyl
acetate. The product was recovered as a wax in 65% yield.
1
Kinetics followed by H NMR demonstrated that the reac-
tion follows a three-step mechanism )Scheme 2), while the
kinetic experiments performed by the UV technique showed
that the third step, i.e. the process 3!4, cannot be detected,
the OD decrease being very small. The cyclic intermediate 2
)not isolable) was indirectly highlighted as a consequence of
the anchimeric assistance of the vicinal amide group, while
the aminoester 3 has been ascertained as an intermediate by
isolation.
4. Experimental
4.1. General
1H NMR and 13C NMR spectra were recorded with a Varian
Gemini 300 )300 MHz) instrument by using CDCl3 as
solvent and the coupling constants )J) are in Hz. IR spectra
were obtained with a Nicolet 210 instrument. UV spectra
and kinetic measurements were recorded on a Perkin±Elmer
Lambda 6 spectrophotometer.
n
max)neat)3393, 1699, 1603, 1460, 1280, 1117, 751, 710;
dH 1.37 )3H, d, J6.5, CHCH3), 3.94 )1H, m, CHCH3), 4.24
)1H, dd, J5.5, 11.1, CHaCHbO), 4.5)1H, dd, J5.2, 11.1,
CHaCHbO), 6.74 )3H, m, Ph), 7.21 )2H, m, Ph), 7.5)3H, m,
Ph), 8.4 )2H, m, Ph); dC 18.1, 47.7, 67.8, 113.2, 117.6,
128.3, 129.3, 129.5, 133, 146.9, 166.5; [Found: C, 75.25;
H, 6.73. C16H17NO2 requires C, 75.27; H, 6.71%].
4.1.1. N-)Methoxyprop-2-yl)benzanilide )1) )see also the
Appendix). 2.2 mL of aniline )24 mmol) and 4.5g
)24 mmol) of )^)-)methoxyprop-2-yl) methanesulphonate
)prepared from )^)-methoxy-2-propanol and methanesulfo-
nylchloride by the usual procedure) were re¯uxed for 40 h
in benzene )20 mL) in the presence of triethylamine )TEA)
)3.4 mL, 24 mmol). Pure N-)2-methoxymethylethyl)aniline
was recovered as an oil in 75% yield after puri®cation by
silica gel chromatography eluting with hexane/ethyl acetate
[dH 1.24 )3H, d, J6.3, CHCH3), 3.39 )3H, s, OCH3), 3.43
)2H, m, OCH2CH), 3.67 )1H, m, CHCH3), 3.83 )1H, bs,
NH), 6.67 )3H, m, Ph), 7.18 )2H, m, Ph)]. The intermediate
4.1.3. 2-)N-phenylamino)propanol )4). It was obtained by
stirring 1 )1.35g, 5mmol) in 10 mL of 8.84 M HCl at about
708C for 6 h. The reaction mixture was concentrated in
vacuo, made alkaline and extracted with ethyl acetate. The
product, after evaporation of the organic solvent, was
recovered as an oil in practically quantitative yield. nmax
product )1.65g, 10 mmol) was dissolved in 15mL of CHCl
3