Simple and convenient synthesis of tertiary benzanilides using dichlorotriphenylphosphorane

Article abstract of DOI:10.1016/S0040-4020(03)00235-7

Various tertiary benzanilide derivatives were effectively synthesized from substituted benzoic acid and N-monoalkylated aniline using dichlorotriphenylphosphorane in chloroform. Yields were generally high, even when an electron-withdrawing group substituted the aromatic ring of aniline, or when an electron-donating group substituted the aromatic ring of benzoic acid. Allyl, Boc, MPM and the Z group were unaffected under these conditions.

Full text of DOI:10.1016/S0040-4020(03)00235-7

Tetrahedron 59 (2003) 2325–2331
Simple and convenient synthesis of tertiary benzanilides
using dichlorotriphenylphosphorane
*
Isao Azumaya, Takako Okamoto, Fumiaki Imabeppu and Hiroaki Takayanagi
School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan
Received 22 November 2002; accepted 5 February 2003
Abstract—Various tertiary benzanilide derivatives were effectively synthesized from substituted benzoic acid and N-monoalkylated aniline
using dichlorotriphenylphosphorane in chloroform. Yields were generally high, even when an electron-withdrawing group substituted the
aromatic ring of aniline, or when an electron-donating group substituted the aromatic ring of benzoic acid. Allyl, Boc, MPM and the Z group
were unaffected under these conditions. q 2003 Published by Elsevier Science Ltd.
1. Introduction
2. Results and discussion
Aromatic amides have been utilized as versatile fragments
to construct frameworks that have various functions such as
molecular recognition, conformational switching and in
biological activities.1–3 Especially, conformational alter-
nation by N-alkylation of aromatic amides from trans4 to
cis5–7 gives folded structures to such molecules.6,7 In the
classical method of synthesizing aromatic amides using
thionyl chloride, the yield is sometimes not so high because
the yield of acid chloride from an acid would not be
quantitative. Various amide coupling reactions have been
developed for peptide synthesis or amidation of weakly
nucleophilic amines, but usually many additives are needed
for completion of such a reaction.8 Some of the Lewis acids,
for example, boron trifluoride etherate,9 tetrachlorosilane,10
and titanium (IV) chloride11 are rarely used for such
couplings, as the yields are usually low, and there is a severe
limitation on substituents of substrates because of their
strong Lewis acidity. In the course of our search for a mild
coupling reagent to couple a carboxylic acid with an
N-alkylated secondary aniline with low nucleophilicity, we
found that dichlorotriphenylphosphorane, which has been
used for a synthesis of acid chloride,12 was highly effective
in a one-step amidation, and that no other additive was
needed in the reaction, contrary to peptide13 or aromatic
copolyamide14 syntheses in which this reagent is used.
In this paper, we report a convenient and effective
amide coupling reaction of N-alkylated secondary
anilines with a substituted benzoic acid using dichloro-
triphenylphosphorane.
The classical peptide coupling reagents15 such as DCC, and
DCC with HOBt gave, at best, only traces of amide for the
coupling reaction of substituted N-methylaniline 1 and
substituted benzoic acid 2 (Scheme 1). The reaction using a
peptide-coupling reagent for bulky or N-alkylated amino
acid, HATU16 or PyBop,17 proceeded to some extent, but
the yields were low because the reaction did not complete
even though several equivalents of the reagent were used,
and because inseparable side products were generated. On
the other hand, dichlorotriphenylphosphorane cleanly
produced the corresponding amide 3, giving the best results
among these dehydrating reagents. During optimization of
the reaction conditions, we eventually found that 2.4 equiv.
of dichlorotriphenylphosphorane effectively completed the
reaction in chloroform at reflux for several hours without
Keywords: tertiary amide; aromatic amide; coupling reagent; cyclic amide.
*
Corresponding author. Tel.: þ81-3-5791-6375; fax: þ81-3-3442-5707;
e-mail: azumayai@pharm.kitasato-u.ac.jp
Scheme 1.
0040–4020/03/$ - see front matter q 2003 Published by Elsevier Science Ltd.
doi:10.1016/S0040-4020(03)00235-7

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I. Azumaya et al. / Tetrahedron 59 (2003) 2325–2331
Table 1. Application of Ph3PCl2 to synthesize various amides
Entry
1
Amine
Carboxylic acid
Product
Time (h)
2.5
Yield (%)
82
2
4.5
81
3
4
2
3.5
4.0
86
81
1
5
2
5.0
80
6
2
2
6.5
86
63
7a
8.75
8b
1
3.0
92
9b
2
5.5
87

I. Azumaya et al. / Tetrahedron 59 (2003) 2325–2331
2327
Table 1 (continued)
Entry
Amine
Carboxylic acid
Product
Time (h)
3.5
Yield (%)
73
10b
2
11b
2
3.5
89
12
4.0
31
13
4.0
59
Reaction conditions. To a solution of an amine (0.5 mmol) and a carboxylic acid (0.525 mmol) in CHCl3 (10 mL) was added Ph3PCl2 (1.2 mmol) with stirring.
The mixture was heated at reflux.
a
Ph3PCl2 (2.8 equiv.).
Ph3PCl2 (3.6 equiv.).
b
other additives to give the corresponding tertiary benz-
anilides 3 (93% yield). Excess addition over the required
amount of dichlorotriphenylphosphorane lowered the yield.
Even a base to trap any hydrogen chloride generated was not
needed for this reaction. When triethylamine (4.8 equiv.)
was added to the reaction mixture, the yield was lowered
to 54% with the generation of acid anhydride (15%).
In optimized conditions, a carboxylic acid, a secondary
amine and dichlorotriphenylphosphorane can be mixed
simultaneously before refluxing. Almost the same yield
(92%) was obtained when the carboxylic acid was added to
the reaction mixture after the amine and dichlorotriphenyl-
phosphorane was mixed and refluxed in chloroform for 2 h.
However, the yield was lowered (to 57%) when the aniline
was added to the reaction mixture after the carboxylic acid
and dichlorotriphenylphosphorane were mixed and refluxed
in chloroform for 2 h.
in 2.5 h (entry 1). The reaction effectively proceeded even
when a benzoic acid or an N-alkylaniline had electron
donating or withdrawing groups (entries 2–9). Relatively
acid labile groups (All, Boc, MPM, Z) were unaffected in
this condition. Where aniline had an MPM group on the
amino nitrogen, additional dichlorotriphenylphosphorane
was needed and the yield was relatively low with a longer
reaction time; which would have been due to the steric effect
of the MPM group (entry 7). Surprisingly, a coupling of
methyl N-methylanthranylate 21 with 2 was successful
(entry 9), even though amino nitrogen has the lowest
nucleophilicity due to the steric effect of the methyl group
on amino nitrogen, an intramolecular hydrogen bonding
with the neighboring carbonyl group and its electron
withdrawing ability. Primary anilines could also couple
with substituted benzoic acids under similar conditions,
though additional dichlorotriphenylphosphorane was
needed to complete the reaction (entries 10, 11).
Next, we applied conditions to synthesize various aromatic
amides (Table 1). N-Methylaniline 4 was coupled with
benzoic acid 5 to give N-methylbenzanilide 6 in 82% yield
Because both an acid and an amine are added simul-
taneously in these conditions, we can easily synthesize

2328
I. Azumaya et al. / Tetrahedron 59 (2003) 2325–2331
Scheme 2.
cyclic amides from secondary aminobenzoic acid. 4- Or
3-(methylamino)benzoic acids coupled effectively with
themselves in this condition to give cyclized aromatic
amides (entries 12, 13), which had previously been
synthesized by a one-pot reaction using tetrachlorosilane.18
These mechanisms were supported by 1H NMR experiments
as follows. When dichlorotriphenylphosphorane was added
to substituted benzoic acid 2 in CDCl3 at room temperature,
peaks, different from those of 2, corresponding to an adduct
of them were observed. The ratio of the adduct increased
with the adding of dichlorotriphenylphosphorane, and
almost all of 2 (.99%) existed as the adduct when
1.5 equiv. of dichlorotriphenylphosphorane had been
added. In the same way, when dichlorotriphenylphosphor-
ane was added to substituted aniline 1, peaks were shifted
to a lower field with the adding of dichlorotriphenyl-
phosphorane, but the shifts did not converge even when
1.5 equiv. of dichlorotriphenylphosphorane had been added.
These results indicate that the rate constant in the resulting
adduct 31 is smaller than that in the resulting adduct 34,
and that the equilibrium constant at which 31 is formed is
larger than that for 34. When 1, 2 and an equivalent of
dichlorotriphenylphosphorane were mixed, 40% of 2
existed as the adduct 31, judged by the integral of the
peaks and the smaller part of 1 than that existed as the
adduct 34, judged by a shift of the chemical shifts.
Additionally, when 1, 2 and 2 equiv. of dichlorotriphenyl-
phosphorane were mixed, almost all of 2 (.99%) existed as
the adduct 31, and some part of 1 still existed in free amino
form. Therefore, 2 equiv. of dichlorotriphenylphosphorane
were needed to complete the reaction, avoiding generation
of the unreactive acid anhydride 33. Additionally, one more
equivalents of dichlorotriphenylphosphorane were needed
when primary anilines were used because the generated
secondary amide would form a complex with 1 equiv. of
dichlorotriphenylphosphorane.20
A possible reaction mechanism is illustrated in Scheme 2.
Initially, substituted benzoic acid rapidly formed an adduct
with dichlorotriphenylphosphorane in equilibrium. The
adduct was gradually converted to an acid chloride 3212
with a small amount of acid anhydride 33; and the acid
chloride rapidly reacted with substituted aniline, which
was in equilibrium with an adduct 34 of dichlorotriphenyl-
phosphorane.19
To confirm that the reaction proceeded via an acid chloride,
benzoyl chloride and N-methylaniline were reacted with or
without dichlorotriphenylphosphorane in chloroform at
reflux. As a result, the reactions were smoothly completed
in 15 min to give N-methylbenzanilide in both cases. This
means the acid chloride 32 was more reactive than the
adduct 31. On the other hand, when benzoic anhydride
instead of benzoyl chloride, and N-methylaniline were
mixed under the same conditions, the reaction did not
proceed in a period of several hours even when dichloro-
triphenylphosphorane was added. In the coupling reaction
of 1 and 2 with dichlorotriphenylphosphorane, the produc-
tion of acid anhydride 33 that would have reduced the yield
of the reaction, could be avoided because the process
producing the amide from acid chloride and amine was
faster. Therefore, the reaction proceeded via the acid
chloride 32 and the aniline, and the rate-determining step
would be the formation of the acid chloride. The reason why
the yield was low when triethylamine was added would be
because the process forming the acid chloride 32 and the
benzoic acid to the unreactive anhydride 33 was accelerated.
3. Conclusion
We developed a highly efficient method for the production

I. Azumaya et al. / Tetrahedron 59 (2003) 2325–2331
2329
of tertiary aromatic amides using dichlorotriphenylphos-
phorane in chloroform. The method is important, especially
for the synthesis of cyclized compounds from N-alkyl-
aminobenzoic acids, as a carboxylic acid and an amine can
be mixed simultaneously. We believe this method provides
advantages for synthesis of various functionalized oligo-
and cyclic aromatic amides. We are currently exploring
such applications.
yellow oil. IR (Nujol): n¼1575, 1598, 1640, 2930 cm21. 1H
NMR: d 2.80 (6H, s), 3.49 (3H, s), 6.57–6.63 (2H, br m),
6.67–6.71 (1H, br m), 6.99 (1H, t, J¼8.0 Hz), 7.06 (2H, d,
J¼7.0 Hz), 7.12 (1H, tt, J¼7.5, 1.5 Hz), 7.22 (2H, t, J¼
7.5 Hz). 13C NMR: d 38.4, 40.4, 113.2, 113.7, 117.1, 126.2,
126.7, 128.2, 129.0, 136.3, 145.3, 149.9, 171.3. MS (DI-EI)
m/z¼254 [Mþ]. HRMS (DI-EI) calcd for C16H18N2O [Mþ]:
254.1419, found 254.1425.
4.2.3. Ethyl 3-[N-methyl-4-(N-methylbenzyloxycarbonyl-
amino)benzoylamino]benzoate (10). Pale yellow oil. IR
4. Experimental
4.1. General
(KBr): n¼1510, 1585, 1603, 1650, 1710, 2980, 3038 cm21
.
1H NMR: d 1.38 (3H, t, J¼7.0 Hz), 3.25 (3H, s), 3.51 (3H,
s), 4.36 (2H, q, J¼7.0 Hz), 5.12 (2H, s), 7.06–7.14 (3H, m),
7.19–7.35 (8H, m), 7.82 (1H, ddd, J¼8.0, 1.5, 1.5 Hz), 7.87
(1H, dd, J¼1.5, 1.5 Hz). 13C NMR: d 14.2, 37.2, 38.5, 61.3,
67.5, 124.4, 127.2, 127.5, 127.8, 128.0, 128.4, 129.1, 129.5,
131.5, 131.8, 132.5, 136.3, 144.4, 145.0, 155.0, 165.6,
169.9. MS (DI-EI) m/z¼446 [Mþ]. HRMS (DI-EI) calcd for
C26H26N2O5 [Mþ]: 446.1842, found 446.1836.
Melting points are uncorrected. IR spectra were recorded on
1
a JASCO FT/IR-460plus spectrometer. H and 13C NMR
spectra were recorded on a Varian UNITY 400 spectro-
meter. Deuteriochloroform was used as solvent unless stated
otherwise, and chemical shifts (d) are referenced to
1
tetramethylsilane or residual protonated solvent. H NMR
measurements for revealing the reaction mechanisms were
performed on a Varian Mercury 300 spectrometer, and
deuteriochloroform was passed through neutral aluminium
oxide (Brockmann I) immediately before its use in the
measurements. High and low mass spectra were obtained on
a JEOL The MStation JMS-700 spectrometer. Column
chromatography was performed by using Wakogel C-200 or
Merck silica gel 60, and thin-layer chromatography was
carried out on 0.25-mm Merck precoated silica gel glass
plates (Art. 5715). All reactions were carried out under an
argon atmosphere. Dehydrated chloroform for the reaction
was purchased from Kanto Chemical Co., Inc. (Cat. No.
08097-05).
4.2.4. Ethyl 4-N-methyl-(4-nitrobenzoyl)aminobenzoate
(12). Pale yellow powder, mp 1218C. IR (KBr): n¼1603,
1
1658, 1722, 2925, 2980 cm21. H NMR: d 1.36 (3H, t,
J¼7.0 Hz), 3.54 (3H, s), 4.34 (2H, q, J¼7.0 Hz), 7.08 (2H,
ddd, J¼9.0, 2.0, 2.0 Hz), 7.45 (2H, ddd, J¼9.0, 2.0, 2.0 Hz),
7.92 (2H, ddd, J¼9.0, 2.0, 2.0 Hz), 8.05 (2H, ddd, J¼9.0,
2.0, 2.0 Hz). 13C NMR: d 14.2, 38.1, 61.3, 123.3, 126.5,
129.1, 129.6, 130.9, 141.6, 147.7, 148.3, 165.4, 168.3.
MS (DI-EI) m/z¼328 [Mþ]. Anal. calcd for C17H16N2O5:
C, 62.19; H, 4.91; N, 8.53, found: C, 62.13; H, 5.07; N,
8.54.
4.2.5. Ethyl 4-[N-allyl-4-(N-methylbenzyloxycarbonyl-
amino)benzoylamino]benzoate (14). Pale yellow oil. IR
(Nujol): n¼1510, 1605, 1655, 1720, 2930 cm21. 1H NMR:
d 1.35 (3H, t, J¼7.0 Hz), 3.26 (3H, s), 4.33 (2H, q, J¼
7.0 Hz), 4.55 (2H, ddd, J¼6.0, 1.5, 1.5 Hz), 5.13 (2H, s),
5.17 (1H, ddd, J¼4.5, 3.0, 1.5 Hz), 5.21 (1H, ddd, J¼11.0,
3.0, 1.5 Hz), 7.06–7.14 (4H, m), 7.22–7.36 (7H, m),
7.90 (2H, ddd, J¼9.0, 2.0, 2.0 Hz). 13C NMR: d 14.3,
37.2, 53.2, 61.1, 67.5, 117.9, 124.4, 126.8, 127.8, 128.0,
128.3, 128.5, 130.0, 130.5, 132.3, 132.8, 136.2, 144.8,
147.8, 155.0, 165.7, 169.3. MS (FAB) m/z¼473 [MþH]þ.
HRMS (FAB) calcd for C28H28N2O5 [Mþ]: 472.1998, found
472.2005.
4.2. General procedures for amide coupling of a
substituted benzoic acid and a substituted aniline using
dichlorotriphenylphosphorane
To a solution of an amine (0.5 mmol) and a carboxylic acid
(0.525 mmol) in dry chloroform (10 mL) under argon,
dichlorotriphenylphosphorane (1.2 mmol) was added with
stirring. The mixture was heated at reflux for several hours
(see Table 1), and the reaction mixture was poured into ice
and extracted with ethyl acetate. The organic layer was
washed with 4N HCl, saturated aqueous NaHCO3 and brine,
dried (Na2SO4), and evaporated to give a crude product,
which was purified by silica gel column chromatography
(eluent: AcOEt–dichloromethane–MeOH) to give a corre-
sponding amide.
4.2.6. Diethyl 5-[N-allyl-4-(N-methylbenzyloxycarbonyl-
amino)benzoylamino]isophthalate (16). Pale yellow
amorphous. IR (KBr): n¼1512, 1600, 1650, 1698, 1710,
2925, 2980, 3078 cm21. 1H NMR: d 1.37 (6H, t, J¼7.0 Hz),
3.24 (3H, s), 4.35 (4H, q, J¼7.0 Hz), 4.55 (2H, d, J¼
6.0 Hz), 5.11 (2H, s), 5.17 (1H, d, J¼6.0 Hz), 5.20 (1H, s),
5.90–6.01 (1H, m), 7.12 (2H, br d, J¼9.0 Hz), 7.22–7.35
(7H, m), 7.89 (2H, d, J¼1.5 Hz), 8.45 (1H, t, J¼1.5 Hz). 13C
NMR: d 14.2, 37.2, 53.2, 61.6, 67.5, 118.5, 124.4, 127.8,
128.1, 128.5, 128.5, 129.4, 131.9, 132.1, 132.3, 132.5,
136.2, 144.0, 144.7, 154.9, 164.9, 169.7. MS (DI-EI)
m/z¼544 [Mþ]. HRMS (FAB) calcd for C31H33N2O7
[MþH]þ: 545.2288, found 545.2288.
4.2.1. Ethyl 4-[N-methyl-4-(N-methylbenzyloxycarbonyl-
amino)benzoylamino]benzoate (3). Pale yellow oil. IR
1
(KBr): n¼1510, 1603, 1638, 1713, 2980, 3065 cm21. H
NMR: d 1.35 (3H, t, J¼7.0 Hz), 3.26 (3H, s), 3.52 (3H, s),
4.33 (2H, q, J¼7.0 Hz), 5.13 (2H, s), 7.06–7.14 (4H, m),
7.23–7.35 (7H, m), 7.91 (2H, ddd, J¼9.0, 2.0, 2.0 Hz). 13C
NMR: d 14.2, 37.2, 38.3, 61.1, 67.5, 124.4, 126.2, 127.8,
128.0, 128.2, 128.4, 129.5, 130.6, 132.3, 136.2, 144.7,
148.9, 155.0, 165.7, 169.8. MS (DI-EI) m/z¼446 [Mþ].
HRMS (FAB) calcd for C26H27N2O5 [MþH]þ: 447.1920,
found 447.1932.
4.2.7. Ethyl 4-[N-4-methoxybenzyl-4-(N-methylbenzyl-
oxycarbonylamino)benzoylamino]benzoate (18). Pale
4.2.2. 3-Dimethylamino-N-methylbenzanilide (8). Pale

2330
I. Azumaya et al. / Tetrahedron 59 (2003) 2325–2331
yellow oil. IR (KBr): n¼1512, 1603, 1650, 1710, 2840,
2940 cm21. 1H NMR: d 1.34 (3H, t, J¼7.0 Hz), 3.25 (3H, s),
3.77 (3H, s), 4.31 (2H, q, J¼7.0 Hz), 5.08 (2H, s), 5.12 (2H,
s), 6.80 (2H, ddd, J¼9.0, 2.0, 2.0 Hz), 6.97 (2H, ddd, J¼9.0,
2.0, 2.0 Hz), 7.09 (2H, br d, J¼9.0 Hz), 7.19 (2H, d, J¼
9.0 Hz), 7.22–7.36 (7H, m), 7.84 (2H, ddd, J¼9.0, 2.0,
2.0 Hz). 13C NMR: d 14.5, 37.5, 53.5, 55.4, 61.4, 67.7,
114.1, 124.6, 127.5, 128.0, 128.3, 128.6, 128.7, 129.4,
129.8, 130.0, 130.7, 132.7, 136.5, 144.9, 147.8, 155.2,
159.2, 166.0, 169.8. MS (FAB) m/z¼553 [MþH]þ. HRMS
(FAB) calcd for C33H32O6N2 [Mþ]: 552.2272, found
552.2260.
Acknowledgements
This work was supported by Grant-in-aid for Scientific
Research from the Ministry of Education, Science Sports
and Culture, Japan.
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4.2.8. Ethyl 4-[N-methyl-4-(N-methyl-tert-butoxycarbo-
nylamino)benzoylamino]benzoate (20). Pale yellow oil.
IR (KBr): n¼1510, 1605, 1648, 1710, 2930, 2980 cm21. 1H
NMR: d 1.36 (3H, t, J¼7.0 Hz), 1.39 (9H, s), 3.19 (3H, s),
3.51 (3H, s), 4.33 (2H, q, J¼7.0 Hz), 7.05–7.10 (4H, m),
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4.2.9. Methyl 2-[N-methyl-4-(N-methylbenzyloxycarbo-
nylamino)benzoylamino]benzoate (22). Pale yellow oil.
IR (KBr): n¼1510, 1603, 1648, 1710, 2950, 3038 cm21. 1H
NMR: d 3.22 (3H, s), 3.42 (3H, s), 3.85 (3H, s), 5.10 (2H, s),
7.02 (2H, br d, J¼8.0 Hz), 7.18–7.29 (5H, m), 7.29–7.38
(4H, m), 7.43 (1H, br t, J¼8.0 Hz), 7.76 (1H, br d, J¼
8.0 Hz). 13C NMR: d 37.3, 38.4, 52.5, 67.4, 124.1, 127.3,
127.7, 128.0, 128.2, 128.4, 129.0, 129.8, 131.6, 133.1,
136.3, 144.2, 144.7, 155.0, 165.9, 169.7. MS (FAB) m/z¼
433 [MþH]þ. HRMS (FAB) calcd for C25H25N2O5
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benzoylamino]benzoate (24). White powder, mp 1308C. IR
1
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(KBr): n¼1590, 1605, 1650, 1703, 2980, 3310 cm21. H
NMR: d 1.40 (3H, t, J¼7.0 Hz), 3.36 (3H, s), 4.37 (2H, q,
J¼7.0 Hz), 5.21 (2H, s), 7.30–7.40 (7H, m), 7.74 (2H, ddd,
J¼9.0, 2.0, 2.0 Hz), 7.81 (2H, ddd, J¼9.0, 2.0, 2.0 Hz), 8.04
(2H, ddd, J¼9.0, 2.0, 2.0 Hz), 8.14 (1H, br s). 13C NMR: d
14.3, 37.3, 60.9, 67.8, 119.1, 125.1, 126.2, 127.8, 128.0,
128.2, 128.6, 130.8, 131.4, 142.1, 146.6, 155.1, 165.1,
166.1. MS (DI-EI) m/z¼432 [Mþ]. Anal. calcd for
C25H24N2O5: C, 69.43; H, 5.59; N, 6.48, found: C, 69.43;
H, 5.61; N, 6.50.
4.2.11. Ethyl 3-[4-(N-methylbenzyloxycarbonylamino)-
benzoylamino]benzoate (26). Pale yellow powder, mp
1028C. IR (KBr): n¼1592, 1608, 1665, 1688, 1715, 2980,
3398 cm21. 1H NMR: d 1.39 (3H, t, J¼7.0 Hz), 3.36 (3H, s),
4.37 (2H, q, J¼7.0 Hz), 5.20 (2H, s), 7.28–7.40 (7H, m),
7.44 (1H, t, J¼7.0 Hz), 7.80–7.86 (3H, m), 8.06 (1H,
dd, J¼8.0, 2.5 Hz), 8.11 (1H, br s), 8.13 (1H, dd,
J¼2.0, 2.0 Hz). 13C NMR: d 14.3, 37.3, 61.2, 67.8,
121.0, 124.6, 125.1, 125.5, 127.7, 128.0, 128.2, 128.5,
129.2, 131.3, 131.5, 136.1, 138.1, 146.5, 155.1, 165.1,
166.2. MS (FAB) m/z¼433 [MþH]þ. Anal. calcd for
C25H24N2O5: C, 69.43; H, 5.59; N, 6.48, found: C, 69.38; H,
5.68; N, 6.57.

I. Azumaya et al. / Tetrahedron 59 (2003) 2325–2331
2331
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