A facile synthesis of 3,4-dialkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones and naphthoxazin-2-ones and their reactions with organolithium and Grignard reagents - Preparation of N-[1-(2′-hydroxyphenyl)alkyl]amides

Article abstract of DOI:10.1139/v04-100

A facile and simple method for the preparation of 3,4-dialkyl-3,4-dihydro- 2H-1,3-benzoxazin-2-ones or naphthoxazin-2-ones in high yields from aminoalkylphenols and aminoalkylnaphthols is described. The reactions of the products obtained with organolithiu

Full text of DOI:10.1139/v04-100

1314
A facile synthesis of 3,4-dialkyl-3,4-dihydro-2H-
1,3-benzoxazin-2-ones and naphthoxazin-2-ones
and their reactions with organolithium and
Grignard reagents — Preparation of N-[1-(2′-
hydroxyphenyl)alkyl]amides
Cristina Cimarelli, Gianni Palmieri, and Emanuela Volpini
Abstract: A facile and simple method for the preparation of 3,4-dialkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones or
naphthoxazin-2-ones in high yields from aminoalkylphenols and aminoalkylnaphthols is described. The reactions of the
products obtained with organolithium and Grignard reagents were studied, and a method for the preparation of N-[1-(2-
hydroxyphenyl)alkyl]-N-alkylamides, which are of pharmaceutical interest, from benzoxazinones was developed. A pos-
sible reaction mechanism is also proposed. The relative configuration of chiral products was determined from confor-
1
mational analysis of H NMR spectra.
Key words: benzoxazinones, naphthoxazinones, organometallic reagents, amide preparation, aminoalkylphenols.
Résumé : On décrit une méthode simple et efficace de préparer avec des rendements élevés des 3,4-dialkyl-3,4-
dihydro-2H-1,3-benzoxazin-2-ones ou naphtoxazin-2-ones à partir d’aminoalkylphénols ou d’aminoalkylnaphtols. On a
étudié les réactions des produits avec les réactifs de Grignard et les organolithiens et on a mis au point une méthode
de préparation de N-[1-(2-hydroxyphényl)alkyl]-N-alkylamides, des produits présentant un intérêt pharmaceutique, à
partir de benzoxazinones. On propose une hypothèse de mécanisme réactionnel. La configuration relative des produits
chiraux a été déterminée par une analyse conformationnelle appliquée aux spectres de résonance magnétique du proton.
Mots clés : benzoxazinones, naphtoxazinones, réactifs organométalliques, préparation d’amides, aminoalkylphénols.
[Traduit par la Rédaction] Cimarelli et al. 1321
Introduction
few methods for their preparation have been reported (10,
12).
3,4-Dialkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones are a
class of compounds studied because of their diverse biologi-
cal properties as potential antimicrobial agents (1), as anti-
inflammatory agents (2), as acetylcholinesterase inhibitors
(3), and as analgesics, bactericides, and muscle relaxants (4).
At the same time they are also known to originate from the
photodegradation of pesticides such as ethiofencarb (5). Sev-
eral synthesis methods for benzoxazinones have been re-
ported in the literature (4, 6–9). All of these methods suffer
from the same drawbacks, specifically the use of toxic solvents
(benzene) or reagents (carbamyl chlorides, isocyanates,
phosgene), or they require a two-step synthesis sequence.
On the other hand, 3,4-dialkyl-3,4-dihydro-2H-1,3-
naphthoxazin-2-ones are known in the literature (10) for
their activity against several bacterial species, and they have
also been used as precursors in the preparation of phosphinic
ligands for asymmetric catalysis (11); however, only very
Recently, we became interested in the synthesis of
aminoalkylphenols (13) and aminoalkylnaphthols (14), two
classes of compounds studied for their pharmaceutical
properties (15) but also widely used as ligands in ligand-
accelerated catalysis (LAC) (16), in particular in the asym-
metric catalyzed addition of organozinc reagents to
aldehydes (17). We have developed a series of synthetic pro-
cedures that lead to aminoalkylphenols and aminoalkylnaph-
thols in a simple and straightforward way.
Now we wish to report a new, direct, and mild method for
the preparation of 3,4-disubstituted 3,4-dihydro-2H-1,3-
benzoxazin-2-ones and naphthoxazin-2-ones that we have
developed using aminoalkylphenols and aminoalkylnaph-
thols as precursors. Moreover, the results of the study of the
reactions of these compounds with alkyllithium and Grig-
nard reagents and a method for the preparation of N-[1-(2-
hydroxyphenyl)alkyl]amides and of the corresponding naph-
thyl derivatives, which are known for their pharmaceutical
properties (10, 18), are described.
Received 10 February 2004. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 2 November 2004.
C. Cimarelli,1 G. Palmieri, and E. Volpini. Dipartimento di
Scienze Chimiche, Università di Camerino, Via S. Agostino
1, I-62032 Camerino, Italy.
Results and discussion
Aminoalkylphenols (1) and aminoalkylnaphthols (4),
when treated with carbonyldiimidazole (Im2CO) in dichloro-
1Corresponding author (e-mail: cristina.cimarelli@unicam.it).
Can. J. Chem. 82: 1314–1321 (2004)
doi: 10.1139/V04-100
© 2004 NRC Canada

Cimarelli et al.
1315
Scheme 1.
Table 1. Synthesis of benzoxazinones 2.
Entry
1
R1
R2
R3
2
Yield (%)a
1ab
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
R*c
Bn
2a
2b
72
91
69
64
65
98
78
93
88
76
84
87
85
78
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1bd
Me
Me
Me
Et
n-Bu Me
n-Bu Bn
n-Bu R*c
n-Bu R*c
Ph
Ph
Ph
Ph
(l)e-1c f
(u)e-1c f
(l)e-1d f
1e
R*c
R*c
R*c
(l)e-2c
(u)e-2c
(l)e-2d
2e
1f
2f
(l)e-1gg
(u)e-1gg
1hh
(l)e-2g
(u)e-2g
2h
Scheme 2.
Bn
(l)e-1i f
(u)e-1i f
1j
R*c
R*c
Me
Bn
(l)e-2i
(u)e-2i
2j
1k
n-Bu Ph
2k
aYields of the pure isolated compounds.
bReference 20.
cR*–NH2 = ( )-1-phenylethylamine.
dReference 21.
e(l) = like (RR, SS); (u) = unlike (RS, SR)
fReference 13a.
methane, in the presence of dimethylaminopyridine (DMAP)
(19), produce the desired 3,4-dialkyl-3,4-dihydro-2H-1,3-
benzoxazin-2-ones (2) (Scheme 1) and naphthoxazin-2-ones
(5) (Scheme 2), respectively, in reasonable reaction times
and in good yields. This procedure allows the one-step prep-
aration of cyclized products in a mild and straightforward
way. It is very simple and quick and does not require dan-
gerous or expensive chemicals. Moreover, when the reaction
is complete, simple filtration of the reaction mixture on a
thin pad of silica gel provides a quick and easy method for
obtaining a high yield of purified product. The silica gel iso-
lates the excess carbonyldiimidazole and DMAP and the ba-
sic by-products. The absolute configuration of chiral centres
remains unaltered under these reaction conditions. The re-
sults obtained for several aminoalkylphenols and amino-
alkylnaphthols are reported in Tables 1 and 2, respectively.
Cyclization with carbonyldiimidazole was previously re-
ported in the literature (22) for the preparation of 1-benzyl-4-
(2-oxo-3,4-dihydro-2H-1,3-benzoxazine-3-yl)piperidine from
1-benzyl-4-(2-hydroxyphenylmethyl)aminopiperidine, a pro-
duct unsubstituted at the C-4 carbon atom. The described
methodology, without DMAP, requires heating of the reac-
tion mixture in THF to reflux and a longer reaction time.
The reactivity of the synthesized 3,4-dialkyl-3,4-dihydro-
2H-1,3-benzoxazin-2-ones (2) towards organometallic re-
agents has been studied, in particular with alkyllithium and
Grignard reagents. 3,4-Dialkyl-3,4-dihydro-2H-1,3-benzoxazin-
2-ones (2) react with organolithiums at 0 °C in toluene in
reasonable times and give satisfactory yields of N-[1-(2-
hydroxyphenyl)alkyl]-N-alkylamides (3) (Scheme 3). Naph-
thoxazin-2-one (5a), under the same reaction conditions,
reacts with n-butyllithium to afford the corresponding amide
(6ab) but only in poor yield (28%). The reaction gives
satisfactory yields with methyllithium, isopropyllithium, n-
butyllithium, and phenyllithium. Only allyl- and benzyl-
Grignard reagents are reactive towards the substrates
studied, while MeMgBr and PhMgCl are nonreactive.
gReference 13d.
hReference 17.
Table 2. Synthesis of naphthoxazinones 5.
Entry
4
R2
R3
5
Yield (%)a
1
2
3
4
4ab
Ph
Ph
Ph
Bn
5a
98
95
95
86
(l)c-4bd
(l)c-4cg
(l)c-4dh
R*e
R*f
R*e
(l)c-5b
(l)c-5c
(l)c-5d
4-MeOC6H4
5
(l)c-4eh
2-Naphthyl
R*e
(l)c-5e
71
aYields of the pure isolated compounds.
bReference 22.
c(l) = like (RR, SS); (u) = unlike (RS, SR).
dReference 17.
eR*–NH2 = ( )-1-phenylethylamine.
fR*–NH2 = ( )-1-(1-naphthyl)ethylamine.
gReference 13a.
hReference 14a.
Scheme 3.
reagent to the carbonyl group of the starting benzoxazinone
is observed, and the reaction produces the original
aminoalkylphenol 1 and the corresponding symmetric
ketone. In fact, GC–MS analysis of the crude mixtures of the
reactions of 2b, 2h, and 2e with 2.5 equiv. of phenyllithium
and butyllithium reveals the chromatographic peaks and
mass spectra of aminoalkylphenols 1b, 1h, and 1e and of
dibutylketone and benzophenone.
Alkyllithiums and Grignard reagents have been used in a
slight excess (10%) with respect to the starting material.
With a large excess, the double addition of organometallic
© 2004 NRC Canada

1316
Can. J. Chem. Vol. 82, 2004
Scheme 4.
Table 3. Synthesis of N-[1-(2′-hydroxyphenyl)alkyl]amides.
Scheme 5.
Entry
2
R4M
3
Yield (%)a
1
2
3
4
5
6
7
8
9
2b
2b
2b
2b
MeLi
n-BuLi
PhLi
AllylMgCl
BnMgCl
n-BuLi
n-BuLi
n-BuLi
i-PrLi
3ba
3bb
3bd
3be
69
90
75
79
50
56
31
43
77
62
28
2b
3bf
(l)b-2d
2e
(l)b-3db
3eb
2h
2h
3hb
Scheme 6.
3hc
10
11
(l)b-2i
5a
n-BuLi
n-BuLi
(l)b-3ib
6ab
aYields of the pure isolated compounds.
b(l) = like (RR, SS); (u) = unlike (RS, SR).
In several cases the reaction proceeds with comparable re-
sults in n-hexane, but when the starting materials are poorly
soluble in this solvent, toluene gave the best results. The re-
sults obtained in the reactions of benzoxazinones 2b, 2d, 2e,
2h, and 2i with some organolithiums and Grignard reagents
are reported in Table 3.
A hypothesized mechanism for these reactions is pre-
sented in Scheme 4. Moreover, it is possible to make some
observations for the behaviour of these compounds when
they are subjected to GC–MS analysis. Within the mass
spectra of pure benzoxazinones 2b and 2e, we observed the
fragmentation pattern corresponding to the enone 7 and the
isocyanate 8, as depicted in Scheme 5. In a similar fashion,
in 1,4-dihydro-2H-3,1-benzoxazin-2-one derivatives, under
flash vacuum pyrolysis conditions, CO2 extrusion was ob-
served (23). Naphthoxazinones 5 under the same conditions
decompose during the gas chromatographic analysis to give
a complex mixture of unidentified products. The final amide
3 decomposes in a similar way, and it is possible to observe
in the mass spectra the peaks corresponding to the enone 7
and the amide 9, as depicted in Scheme 6 for 3bb, 3db, 3bd,
3bf, and 3eb.
Stereochemistry
The relative configurations of benzoxazinones and naphth-
oxazinones were assigned by analogy with the chiral starting
aminophenols. To confirm that cyclization took place with
retention of configuration, the stereochemistry of the pre-
pared oxazinones was confirmed by conformational analysis
on the diastereomeric couples (R,R)-2c/(4S,1R)-2c and
(R,R)-2i/(4S,1R)-2i. The more stable conformations for
(R,R)- and (4S,1′R)-2c and (R,R)- and (4S,1′R)-2i, obtained
by PM3 semi-empirical minimization, are reported in Fig. 1.
1
A comparison of the differences in H NMR chemical shifts
(∆δ) observed for the diastereomeric couples, resulting from
the anisotropic effects of the phenyl and carbonyl groups, as
indicated in Fig. 1, allowed us to assign relative configura-
tions.
© 2004 NRC Canada

Cimarelli et al.
1317
1
Fig. 1. Minimized conformations for the (R,R)- and (4S,1′R)-2c and the (R,R)- and (4S,1′R)-2i oxazinones with observed H NMR ∆δ
(ppm) resulting from anisotropic effects.
(d, 1H, J = 12.8 Hz), 6.80–7.20 (m, 9H), and 13.40 (bs, 1H).
Experimental
13C NMR (75 MHz, CDCl3) δ: 13.9, 22.6, 28.4, 35.7, 51.8,
63.6, 116.8, 118.9, 127.5, 128.4, 128.5, 128.7, 129.2, 132.4,
157.4, and 165.6. Anal. calcd. (%) for C18H23NO, MW
General methods
Proton and 13C NMR spectra were recorded with a Varian
269.386: C 80.26, H 8.61, N 5.20; found: C 80.21, H 8.86,
VXR 300 instrument. Chemical shifts are given in ppm
N 5.37.
downfield from Me4Si in CDCl3 solution. Coupling con-
stants are given in Hz. IR spectra were recorded with a
Perkin-Elmer 257 spectrometer. GC–MS analyses were per-
formed with a HP-59970 workstation consisting of a HP-
5890 gas chromatograph equipped with a methyl silicone
2-[1-(Methylamino)-1-phenylethyl]phenol (1j)
Yield 91%. Oil. IR νmax (liquid film) (cm–1): 3308, 2981,
1
1494, 1262, 820, 754, and 720. H NMR (300 MHz, CDCl3)
δ: 1.86 (s, 3H), 2.29 (s, 3H), 2.65 (s, 1H), 6.66–7.44 (m,
9H), and 12.30 (s, 1H). 13C NMR (75 MHz, CDCl3) δ: 24.6,
28.9, 64.7, 117.4, 118.8, 126.7, 127.5, 128.5, 128.6, 129.1,
129.8, 144.7, and 158.3. Anal. calcd. (%) for C15H17NO,
MW 227.30: C 79.26, H 7.54, N 6.16; found: C 79.48, H
7.32, N 6.27.
capillary column and a HP-5970 mass detector. All melting
points are uncorrected. Toluene and hexane were dried by
refluxing over sodium wires and then distilled into a dry re-
ceiver under a nitrogen atmosphere. All reagents were of
commercial quality from freshly opened containers. Com-
mercial alkyllithium and Grignard reagent solutions
(Aldrich) were used in a dry atmosphere.
2-[1-(Benzylamino)-1-phenylpentyl]phenol (1k)
Yield 84%. Oil. IR νmax (liquid film) (cm–1): 2954, 1606,
Preparation of starting aminoalkylphenols 1a–1i and
aminoalkylnaphthols 4a–4e
Starting aminoalkylphenols and aminoalkylnaphthols were
prepared according to previously reported procedures (11)
using ( )-phenylethylamine as the chiral starting material in-
stead of the (R) enantiomer. Spectral data for the unknown
starting materials 1e, 1f, 1j, and 1k follow.
1
1455, 1295, 753, and 699. H NMR (300 MHz, CDCl3) δ:
0.99 (t, 3H, J = 7.0 Hz), 1.20–1.60 (m, 4H), 2.30–2.70 (m,
3H), 3.62 (bs, 2H), 6.70–7.70 (m, 14H), and 12.20 (bs, 1H).
13C NMR (75 MHz, CDCl3) δ: 14.4, 23.3, 25.4, 36.1, 47.0,
55.8, 117.5, 118.9, 126.7, 127.1, 128.0, 128.4, 129.0, 129.1,
129.2, 139.0, 143.8, 158.1, 163.5, and 175.1. Anal. calcd.
(%) for C24H27NO, MW 345.48: C 83.44, H 7.88, N 4.05;
found: C 83.30, H 7.57, N 4.23.
2-[1-(Methylamino)pentyl]phenol (1e)
Yield 98%. Oil. IR νmax (liquid film) (cm–1): 2950, 2836,
1
Preparation of benzoxazinones 2a–2k and
naphthoxazinones 5a–5e
1482, 1447, and 1270. H NMR (CDCl3) δ: 0.89 (t, 3H, J =
6.6 Hz), 1.10–1.50 (m, 4H), 1.60 (bs, 1H), 1.60–1.90 (m,
2H), 2.43 (s, 3H), 3.61 (t, 1H, J = 7.0 Hz), 6.70–7.30 (m, 4
H), and 9.00 (s, 1H). Anal. calcd. (%) for C12H19NO, MW
193.288: C 74.45, H 9.91, N 7.25; found: C 74.56, H 10.04,
N 7.27.
Aminoalkylphenols 1b–1i (2 mmol) or aminoalkyl-
naphthols 3a–3e (2 mmol), in a 50-mL round-bottom flask
equipped with a magnetic stirring bar, were dissolved in
10 mL CH2Cl2 at room temperature (RT) to which was
added DMAP (0.2 mmol) and carbonyldiimidazole (3 mmol).
The reaction mixture was allowed to stand at RT for 1 h and
then the mixture was filtered on a thin pad of silica gel, af-
fording almost pure 2a–2k or 5a–5e. When necessary, the fi-
nal benzoxazinones or naphthoxazinones were purified
further by recrystallization or chromatographic separation.
2-[1-(Benzylamino)pentyl]phenol (1f)
Yield 80%. Oil. IR νmax (liquid film) (cm–1): 2968, 2943,
1
2870, 1527, 1488, and 1243. H NMR (300 MHz, CDCl3) δ:
0.83 (t, 3H, J = 7.0 Hz), 1.09–1.34 (m, 4H), 1.62–1.85 (m,
3H), 3.60 (d, 1H, J = 12.8 Hz), 3.74 (t, 1H, J = 7.2 Hz), 3.83
© 2004 NRC Canada

1318
Can. J. Chem. Vol. 82, 2004
Spectral data for the products obtained follow. In the numer-
ical designations of the compounds below, the prefixes (l)
and (u) mean like (RR, SS) and unlike (RS, SR), respectively.
Anal. calcd. (%) for C18H19NO2, MW 281.349: C 76.84, H
6.81, N, 4.98; found: C 76.63, H 6.90, N, 5.14.
4-Butyl-3-methyl-3,4-dihydro-1,3-benzo[e][1,3]oxazin-2-
one (2e)
3-(1′-Phenylethyl)-3,4-dihydro-1,3-benzo[e][1,3]oxazin-2-
one (2a)
White crystals; mp 127–129 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 2924, 1712, 1463, 1230, and 757. H
1
White crystals; mp 98–100 °C (n-hexane/CH2Cl2). IR νmax
(Nujol) (cm–1): 2930, 1712, 1500, 1415, 1238, 797, and 734.
1H NMR (300 MHz, CDCl3) δ: 1.68 (d, 3H, J = 7.0 Hz),
3.91 (d, 1H, J = 14.3 Hz), 4.30 (d, 1H, J = 14.6 Hz), 5.92 (q,
1H, J = 7.2 Hz), and 6.95–7.43 (m, 9H). 13C NMR
(75 MHz, CDCl3) δ: 15.2, 41.3, 53.8, 116.3, 117.8, 124.3,
125.7, 127.6, 128.1, 128.9, 129.0, 138.8, 149.7, and 151.3.
MS (EI) m/z (%): 253 (M+, 10), 148 (7), 105 (100), and 77
(18). Anal. calcd. (%) for C16H15NO2, MW 253.30: C 75.87,
H 5.97, N 5.53; found: C 75.92, H 6.21, N 5.79.
NMR (300 MHz, CDCl3) δ: 0.86 (t, 3H, J = 6.8 Hz), 1.00–
1.40 (m, 4H), 1.65–2.00 (m, 2H), 3.12 (s, 3H), 4.41 (dd, 1H,
J = 3.7, 6.2 Hz), and 7.00–7.40 (m, 4H). 13C NMR
(75 MHz, CDCl3) δ: 14.1, 22.7, 25.5, 34.9, 35.3, 60.4, 116.4,
122.1, 124.2, 125.7, 129.0, 150.1, and 151.7. MS (EI) m/z
(%): 219 (M+, 1), 162 (100), 118 (7), and 91 (19). Anal.
calcd. (%) for C13H17NO2, MW 219.280: C 71.21, H 7.81, N
6.39; found: C 70.97, H 7.68, N 6.45.
3-Benzyl-4-butyl-3,4-dihydro-1,3-benzo[e][1,3]oxazin-2-one
(2f)
3-Benzyl-4-methyl-3,4-dihydro-1,3-benzo[e][1,3]oxazin-2-
one (2b)
White crystals; mp 48–50 °C (n-hexane/CH2Cl2). IR νmax
(Nujol) (cm–1): 2982, 2914, 1741, 1438, 1255, 757, and 743.
1H NMR (300 MHz, CDCl3) δ: 0.79 (t, 3H, J = 6.7 Hz),
1.00–1.60 (m, 4H), 1.50–1.90 (m, 2H), 4.20 (d, 1H, J =
15.3 Hz), 4.28 (dd, 1H, J = 3.5, 6.9 Hz), 5.24 (d, 1H, J =
15.3 Hz), and 6.92–7.18 (m, 9H). 13C NMR (75 MHz,
CDCl3) δ: 13.9, 22.4, 25.5, 34.6, 50.1, 56.7, 116.3, 122.3,
124.0, 125.6, 127.9, 127.9, 1278.0, 128.7, 128.8, 136.0, and
149.9. MS (EI) m/z (%): 295 (M+, 2), 238 (100), 155 (17),
and 91 (98). Anal. calcd. (%) for C19H21NO2, MW 295.376:
C 75.87, H 5.97, N 5.53; found: C 75.77, H 5.91, N 5.63.
White crystals; mp 110–112 °C (n-hexane). IR νmax
(Nujol) (cm–1): 2924, 1709, 1497, 1423, 1371, 1253, 761,
1
and 746. H NMR (300 MHz, CDCl3) δ: 1.44 (d, 3H, J =
6.6 Hz), 4.28 (d, 1H, J = 15.4 Hz), 4.39 (q, 1H, J = 6.6 Hz),
5.26 (d, 1H, J = 15.4 Hz), and 7.00–7.50 (m, 9H). 13C NMR
(75 MHz, CDCl3) δ: 22.5, 50.1, 52.9, 116.7, 124.1, 124.5,
125.4, 128.1, 128.2, 129.0, 129.1, 136.2, 149.4, and 151.8.
MS (EI) m/z (%): 253 (M+, 9), 238 (20), 162 (11), 120 (48),
and 91 (100). Anal. calcd. (%) for C16H15NO2, MW 253.30:
C 75.87, H 5.97, N 5.53; found: C 75.78, H 5.90, N 5.64.
(l)-( )-4-Methyl-3-(1′-phenylethyl)-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one ((l)-2c)
(l)-( )-4-Butyl-3-(1′-phenylethyl)-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one ((l)-2g)
Oil. IR νmax (liquid film) (cm–1): 2932, 1715, 1503, 1423,
Oil. IR νmax (liquid film) (cm–1): 2930, 1718, 1500, 1429,
1
1369, 1248, 760, and 744. H NMR (300 MHz, CDCl3) δ:
1
1364, 1251, 762, and 743. H NMR (300 MHz, CDCl3) δ:
1.43 (d, 3H, J = 6.6 Hz), 1.81 (d, 3H, J = 7.3 Hz), 4.15 (q,
1H, J = 6.6 Hz), 5.65 (q, 1H, J = 7.0 Hz), and 7.00–7.60 (m,
9H). 13C NMR (75 MHz, CDCl3) δ: 18.4, 29.9, 50.5, 55.7,
116.6, 124.4, 124.5, 126.5, 127.5, 128.0, 128.7, 128.9, 139.6,
149.8, and 152.2. Anal. calcd. (%) for C17H17NO2, MW
267.322: C 76.38, H 6.41, N 5.24; found: C 76.29, H 6.54,
N 5.18.
0.82 (t, 3H, J = 6.2 Hz), 0.87–1.30 (m, 4H), 1.60–1.80 (m,
2H), 1.80 (d, 3H, J = 7.3 Hz), 4.01 (dd, 1H, J = 3.7, 8.0 Hz),
5.63 (q, 1H, J = 7.3 Hz), and 6.80–7.60 (m, 9H). Anal.
calcd. (%) for C16H23NO2, MW 309.402: C 77.64, H 7.49, N
4.53; found: C 77.63, H 7.61, N, 4.43.
(u)-( )-4-Butyl-3-(1′-phenylethyl)-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one ((u)-2g)
(u)-( )-4-Methyl-3-(1′-phenylethyl)-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one ((u)-2c)
Oil. IR νmax (liquid film) (cm–1): 2935, 1720, 1432, 1231,
1
Oil. IR νmax (liquid film) (cm–1): 2930, 1712, 1428, 1243,
and 762. H NMR (300 MHz, CDCl3) δ: 0.63 (t, 3H, J =
1
6.8 Hz), 0.87–1.30 (m, 4H), 1.60–1.80 (m, 2H), 1.65 (d, 3H,
J = 7.3 Hz), 4.33 (d, 1H, J = 8.4 Hz), 5.66 (q, 1H, J =
7.0 Hz), and 6.80–7.60 (m, 9H). Anal. calcd. (%) for
C16H23NO2, MW 309.402: C 77.64, H 7.49, N 4.53; found:
C 77.51, H 7.63, N 4.71.
763, and 748. H NMR (300 MHz, CDCl3) δ: 0.83 (d, 3H,
J = 6.6 Hz), 1.66 (d, 3H, J = 7.0 Hz), 4.47 (q, 1H, J =
6.6 Hz), 5.70 (q, 1H, J = 7.1 Hz), and 7.00–7.60 (m, 9H).
Anal. calcd. (%) for C17H17NO2, MW 267.322: C 76.38, H
6.41, N 5.24; found: C 76.22, H 6.63, N 5.20.
3-Benzyl-4-phenyl-3,4-dihydro-1,3-benzo[e][1,3]oxazin-2-
one (2h)
(l)-( )-4-Ethyl-3-(1′-phenylethyl)-3,4-dihydro-
benzo[e][1,3]oxazin-2-one ((l)-2d)
Oil. IR νmax (liquid film) (cm–1): 2948, 1690, 1607, 1412,
White crystals; mp 130–134 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 2937, 1705, 1599, 1424, 1356, 745, and
698. 1H NMR (300 MHz, CDCl3) δ: 3.76 (d, 1H, J =
15.2 Hz), 5.26 (s, 1H), 5.40 (d, 1H, J = 15.2 Hz), and 6.83–
7.45 (m, 14H). 13C NMR (75 MHz, CDCl3) δ: 49.7, 60.9,
116.7, 121.7, 124.6, 127.0, 127.3, 128.2, 128.6, 128.9,
129.1, 129.2, 129.5, 135.7, 140.7, 148.6, and 151.2. MS (EI)
m/z (%): 315 (M+, 7), 224 (9), 181 (100), 132 (13), 106 (14),
1
1350, 760, and 695. H NMR (300 MHz, CDCl3) δ: 0.75 (t,
3H, J = 7.4 Hz), 1.79 (d, 3H, J = 7.3 Hz), 1.64–1.88 (m,
2H), 3.97 (dd, 1H, J = 3.7, 7.4 Hz), 5.62 (q, 1H, J = 7.3 Hz),
and 6.78–7.60 (m, 9H). 13C NMR (75 MHz, CDCl3) δ: 8.5,
18.2, 30.7, 55.6, 55.9, 116.2, 123.7, 123.9, 125.5, 127.5,
127.9, 128.7, 128.8, 139.3, 150.2, and 152.4. MS (EI) m/z
(%): 281 (M+, 1), 252 (41), 148 (87), 105 (100), and 77 (18).
© 2004 NRC Canada

Cimarelli et al.
1319
and 91 (34). Anal. calcd. (%) for C21H17NO2, MW 315.365:
C 79.98, H 5.43, N 4.44; found: C 80.05, H 5.62, N 4.64.
202 (14), and 91 (20). Anal. calcd. (%) for C25H19NO2, MW
365.424: C 82.17, H 5.24, N 3.83; found: C 82.38, H 4.97,
N 3.62.
(l)-( )-4-Phenyl-3-(1′-phenylethyl)-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one ((l)-2i)
(l)-( )-1-Phenyl-2-(1′-phenylethyl)-1,2-dihydro-
Oil. IR νmax (liquid film) (cm–1): 2944, 1689, 1610, 1404,
naphtho[1,2-e][1,3]oxazin-3-one ((l)-5b)
1
White crystals; mp 174–176 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 3064, 3027, 1712, 1628, 1588, 1517,
1438, 1158, 1029, 959, 882, 768, and 614. 1H NMR
(300 MHz, CDCl3) δ: 1.38 (d, 3H, J = 7.2 Hz), 5.69 (s, 1H),
5.86 (q, 1H, J = 7.2 Hz), and 7.20–7.80 (m, 16H). 13C NMR
(75 MHz, CDCl3) δ: 16.9, 55.6, 56.4, 116.6, 117.1, 121.9,
125.0, 127.3, 127.4, 128.1, 128.3, 128.5, 128.6, 129.0,
129.1, 129.2, 130.1, 131.0, 138.6, 142.4, 146.8, and 151.5.
Anal. calcd. (%) for C26H21NO2; MW 379.45: C 82.30, H
5.58, N 3.69; found: C 82.28, H 5.72, N 3.40.
1352, 758, and 696. H NMR (300 MHz, CDCl3) δ: 1.28 (d,
3H, J = 7.2 Hz), 5.02 (s, 1H), 5.81 (q, 1H, J = 7.2 Hz), and
6.83–7.48 (m, 14H). 13C NMR (75 MHz, CDCl3) δ: 17.3,
56.1, 58.5, 116.7, 123.8, 124.6, 125.9, 126.3, 128.1, 128.3,
128.5, 128.9, 129.0, 129.4, 138.9, 143.6, 148.6, and 151.7.
MS (EI) m/z (%): 329 (M+, 11), 224 (7), 182 (40), 181 (85),
146 (27), 105 (100), and 77 (19). Anal. calcd. (%) for
C22H19NO2, MW 329.392: C 80.22, H 5.81, N 4.25; found:
C 80.37, H 5.90, N 4.43.
(u)-( )-4-Phenyl-3-(1′-phenylethyl)-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one ((u)-2i)
(l)-( )-2-(1′-Naphthalen-2-yl-ethyl)-1-phenyl-1,2-dihydro-
naphtho[1,2-e][1,3]oxazin-3-one ((l)-5c)
Oil. IR νmax (liquid film) (cm–1): 2951, 1692, 1413, 1332,
1
White crystals; mp 142–144 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 3060, 1712, 1420, 1222, 1184, 804, and
730. 1H NMR (300 MHz, CDCl3) δ: 1.41 (d, 3H, J =
7.2 Hz), 5.37 (s, 1H), 6.46 (q, 1H, J = 7.2 Hz), and 7.20–
8.00 (m, 18H). 13C NMR (75 MHz, CDCl3) δ: 17.2, 53.2,
55.1, 116.1, 116.8, 121.6, 123.1, 124.6, 124.7, 126.1, 126.2,
126.9, 127.2, 127.3, 127.5, 128.4, 128.7, 128.8, 129.0,
129.7, 129.8, 130.7, 131.9, 133.2, 133.9, 142.4, 146.1, and
152.0. Anal. calcd. (%) for C30H23NO2, MW 429.51: C
83.89, H 5.40, N 3.26; found: C 83.72, H 5.28, N 3.35.
and 760. H NMR (300 MHz, CDCl3) δ: 1.67 (d, 3H, J =
7.3 Hz), 5.26 (q, 1H, J = 7.3 Hz), 5.43 (s, 1H), and 6.80–
7.40 (m, 14H). MS (EI) m/z (%): 329 (M+, 9), 182 (37), 181
(82), 105 (100), and 77 (16). Anal. calcd. (%) for C22H19NO2,
MW 329.392: C 80.22, H 5.81, N 4.25; found: C 80.31, H
5.69, N 4.15.
3,4-Dimethyl-4-phenyl-3,4-dihydro-1,3-benzo[e][1,3]oxazin-
2-one (2j)
Oil. IR νmax (liquid film) (cm–1): 1710, 1414, 1377, 1232,
1
778, 745, and 700. H NMR (300 MHz, CDCl3) δ: 1.98 (s,
3H), 2.77 (s, 3H), and 6.60–7.20 (m, 9H). 13C NMR (75
MHz, CDCl3) δ: 26.6, 32.0, 64.8, 116.3, 124.5, 127.0, 127.3,
127.4, 128.3, 129.0, 129.1, 143.5, 147.9, and 150.9. MS (EI)
m/z (%): 253 (M+, 4), 238 (10), 195 (89), 181 (40), 165 (23),
and 152 (29). Anal. calcd. (%) for C16H15NO2, MW 253.30:
C 75.87, H 5.97, N 5.53; found: C 75.24, H 5.72, N, 5.46.
(l)-( )-1-(4-Methoxy-phenyl)-2-(1′-phenylethyl)-1,2-
dihydro-naphtho[1,2-e][1,3]-oxazin-3-one ((l)-5d)
White crystals; mp 151–153 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 3061, 2935, 1716, 1512, 1223, 1183,
1
1032, 814, 736, and 699. H NMR (300 MHz, CDCl3) δ:
1.38 (d, 3H, J = 7.3 Hz), 3.71 (s, 3H), 5.62 (s, 1H), 5.81 (q,
1H, J = 7.3 Hz), and 6.75–7.80 (m, 15H). 13C NMR
(75 MHz, CDCl3) δ: 17.1, 55.2, 55.4, 56.5, 114.6, 116.9,
117.0, 117.1, 122.0, 125.1, 127.5, 128.2, 128.4, 128.7,
129.1, 129.4, 130.1, 131.1, 134.6, 138.8, 146.7, 151.6, and
159.7. Anal. calcd. (%) for C27H23NO3, MW 409.476: C
79.20, H 5.66, N 3.42; found: C 79.02, H 5.43, N, 3.15.
3-Benzyl-4-butyl-4-phenyl-3,4-dihydro-1,3-
benzo[e][1,3]oxazin-2-one (2k)
Oil. IR νmax (liquid film) (cm–1): 2957, 1713, 1455, 1389,
1
1231, 748, and 704. H NMR (300 MHz, CDCl3) δ: 0.67 (t,
3H, J = 6.4 Hz), 0.75–1.30 (m, 4H), 2.00–2.40 (m, 2H), 4.07
(d, 1H, J = 15.0 Hz), 4.62 (d, 1H, J = 15.0 Hz), and 6.50–
7.42 (m, 14H). 13C NMR (75 MHz, CDCl3) δ: 13.9, 22.4,
25.4, 38.6, 49.1, 69.2, 115.8, 124.4, 125.5, 127.3, 128.0,
128.2, 128.3, 128.5, 128.6, 128.7, 129.3, 138.3, 144.1,
148.8, and 152.0. MS (EI) m/z (%): 371 (M+, 1), 314 (100),
222 (13), and 91 (95). Anal. calcd. (%) for C25H25NO2, MW
371.47: C 80.83, H 6.78, N 3.77; found: C 80.57, H 6.53, N
3.84.
(l)-( )-1-Naphthalen-2-yl-2-(1′-phenylethyl)-1,2-dihydro-
naphtho[1,2-e][1,3]oxazin-3-one ((l)-5e)
White crystals; mp 139–141 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 3058, 1712, 1717, 1634, 1517, 1222,
1
1184, 814, 739, and 699. H NMR (300 MHz, CDCl3) δ:
1.31 (d, 3H, J = 7.3 Hz), 5.81 (s, 1H), 5.85 (q, 1H, J =
7.3 Hz), and 7.30–7.90 (m, 18H). 13C NMR (75 MHz,
CDCl3) δ: 17.1, 55.9, 55.4, 56.6, 116.4, 117.2, 122.0, 125.0,
125.1, 126.4, 126.7, 129.8, 127.5, 127.9, 128.2, 128.3,
128.4, 128.7, 129.1, 129.1, 129.7, 130.3, 131.1, 133.3,
138.7, 139.7, 146.9, and 151.6. Anal. calcd. (%) for
C30H23NO2, MW 429.509: C 83.89, H 5.40, N 3.26; found:
C 83.67, H 5.58, N 3.44.
2-Benzyl-1-phenyl-1,2-dihydro-naphtho[1,2-e][1,3]oxazin-
3-one (5a)
Oil. IR νmax (liquid film) (cm–1): 3063, 3030, 1709, 1635,
1446, 1218, 1085, 994, 826, 743, and 703. 1H NMR
(300 MHz, CDCl3) δ: 3.93 (d, 1H, J = 15.4 Hz), 5.40 (d, 1H,
J = 15.4 Hz), 5.73 (s, 1H), and 7.20–7.90 (m, 16H). 13C
NMR (75 MHz, CDCl3) δ: 49.3, 58.8, 114.4, 117.2, 122.5,
125.3, 127.6, 128.2, 128.3, 128.4, 129.1, 129.1, 129.2,
129.4, 129.8, 130.6, 131.1, 135.7, 139.5, 147.1, and 151.1.
MS (EI) m/z (%): 365 (M+, 11), 288 (6), 260 (5), 231 (100),
Reaction of oxazinones 2b, 2d, 2e, 2h, 2i, and 5a with
organolithiums and Grignard reagents
Oxazinones 2 or 5 (3 mmol) in a three-necked round-
bottom flask, equipped with a magnetic stirring bar and rub-
© 2004 NRC Canada

1320
Can. J. Chem. Vol. 82, 2004
ber septum, were dissolved in anhydrous toluene (10 mL)
under a nitrogen atmosphere at 0 °C and were then treated
with 3.3 mmol of a commercial solution of alkyllithium or
Grignard reagent. The reaction was monitored by TLC using
n-hexane/ethyl acetate (80/20) as an eluent. After a variable
time (2–3 h) at RT, when the starting material was con-
sumed, the reaction was quenched with a NH4Cl saturated
solution (5 mL) and the brine was extracted with CH2Cl2
(2 × 20 mL). The solution was dried with anhydrous Na2SO4
then filtered, and the solvent was evaporated under reduced
pressure. Chromatographic separation of the crude oil ob-
tained, with cyclohexane/ethyl acetate (80/20) as an eluent
afforded products 3 and 6 in yields of 28% and 90%, respec-
tively. Spectral data follow.
N-Benzyl-N-[1-(2-hydroxyphenyl)ethyl]-2-phenylacetamide
(3bf)
Oil. IR νmax (liquid film) (cm–1): 3138, 2966, 1630, 1484,
1
1445, 1223, and 758. H NMR (300 MHz, CDCl3) δ: 1.51
(d, 3H, J = 7.2 Hz), 3.54 (d, 1H, J = 15.4 Hz), 3.66 (d, 1H,
J = 15.4 Hz), 4.46 (s, 2H), 6.16 (q, 1H, J = 7.2 Hz), 6.70–
7.40 (m, 14H), and 9.13 (bs, 1H). 13C NMR (75 MHz,
CDCl3) δ: 17.4, 41.4, 46.8, 47.8, 117.8, 119.6, 125.9, 126.9,
127.3, 127.7, 128.9, 129.0, 129.2, 129.9, 134.3, 137.5,
142.8, 156.0, and 175.3. Anal. calcd. (%) for C23H23NO2,
MW 345.434: C 79.97, H 6.71, N 4.05; found: C 79.78, H
6.90, N 4.23.
(l)-( )-[1-(2-Hydroxyphenyl)propyl]-(1′-phenylethyl)-
pentanamide ((l)-3db)
Oil. IR νmax (liquid film) (cm–1): 3138, 2965, 1624, 1487,
1451, 1232, and 760. 1H NMR (300 MHz, CDCl3) δ: 0.70 (t,
3H, J = 6.8 Hz), 0.90–1.14 (m, 2H), 1.02 (t, 3H, J = 7.1 Hz),
1.36–1.58 (m, 2H), 1.66–1.90 (m, 2H), 1.85 (d, 3H, J =
7.0 Hz), 1.94–2.34 (m, 2H), 4.80 (m, 1H), 5.90 (bs, 1H),
6.60–7.40 (m, 9H), and 9.45 (bs, 1H). 13C NMR (75 MHz,
CDCl3) δ: 11.8, 13.8, 19.5, 22.4, 24.3, 27.6, 35.8, 51.1, 55.3,
117.6, 119.6, 124.0, 125.9, 126.4, 127.2, 128.6, 129.7,
141.3, 156.8, and 178.0. Anal. calcd. (%) for C22H29NO2,
MW 339.471: C 77.84, H 8.61, N 4.13; found: C 77.58, H
8.34, N 3.92.
N-Benzyl-N-[1-(2-hydroxyphenyl)ethyl]acetamide (3ba)
Oil. IR νmax (liquid film) (cm–1): 3138, 2966, 1630, 1484,
1
1445, 1223, and 758. H NMR (300 MHz, CDCl3) δ: 1.49
(d, 3H, J = 7.1 Hz), 2.04 (s, 3H), 4.47 (s, 2H), 6.11 (q, 1H,
J = 7.1 Hz), 6.80–7.40 (m, 9H), and 9.20 (bs, 1H). 13C NMR
(75 MHz, CDCl3) δ: 17.4, 22.5, 27.1, 47.3, 47.5, 117.9,
119.6, 125.9, 126.8, 127.6, 129.1, 129.8, 137.4, 156.0, and
174.9. Anal. calcd. (%) for C17H19NO2, MW 269.34: C
75.81, H 7.11, N 5.20; found: C 75.58, H 7.38, N 5.32.
N-Benzyl-N-[1-(2-hydroxyphenyl)ethyl]pentanamide (3bb)
Oil. IR νmax (liquid film) (cm–1): 3165, 2948, 1620, 1493,
1448, 1238, and 740. 1H NMR (300 MHz, CDCl3) δ: 0.81 (t,
3H, J = 7.1 Hz), 1.12–1.34 (m, 2H), 1.46 (d, 3H, J =
7.0 Hz), 1.50–1.68 (m, 2H), 2.21 (dt, 2H, J = 3.2, 15.0 Hz),
4.45 (s, 2H), 6.12 (q, 1H, J = 7.2 Hz), 6.80–7.20 (m, 9H),
and 9.10 (bs, 1H). 13C NMR (75 MHz, CDCl3) δ: 14.1, 22.6,
22.7, 26.2, 42.7, 51.9, 58.7, 117.1, 119.4, 125.9, 127.8,
128.5, 128.6, 128.9, 129.0, 129.8, 138.8, and 157.5. Anal.
calcd. (%) for C20H25NO2, MW 311.42: C 77.14, H 8.09, N
4.50; found: C 77.11, H 8.06, N 4.49.
N-[1-(2-Hydroxyphenyl)pentyl]-N-methylpentanamide (3eb)
Oil. IR νmax (liquid film) (cm–1): 3172, 2957, 1603, 1488,
1457, 1242, and 754. 1H NMR (300 MHz, CDCl3) δ: 0.92 (t,
3H, J = 7.0 Hz), 0.93 (t, 3H, J = 7.0 Hz), 1.18–1.50 (m, 6H),
1.56–1.74 (m, 2H), 1.78–2.16 (m, 2H), 2.36 (dt, 2H, J = 3.7,
7.5 Hz), 2.79 (s, 3H), 5.79 (dd, 1H, J = 6.2, 9.5 Hz), 6.80–
6.98 (m, 2H), 7.16–7.29 (m, 2H), and 9.22 (s, 1H). 13C
NMR (75 MHz, CDCl3) δ: 14.0, 14.2, 22.6, 22.7, 27.3, 28.8,
29.1, 29.2, 33.8, 50.7, 117.7, 119.3, 124.7, 126.8, 129.5,
156.4, and 176.4. MS (EI) m/z (%): 277 (M+, 27), 220 (12),
162 (40), 136 (100), 133 (60), 116 (35), and 107 (43). Anal.
calcd. (%) for C17H27NO2, MW 277.402: C 73.61, H 9.81, N
5.05; found: C 73.48, H 9.47, N 5.24.
N-Benzyl-N-[1-(2-hydroxyphenyl)ethyl]benzamide (3bd)
White crystals; mp 160–162 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 3138, 2966, 1630, 1484, 1445, 1223,
N-Benzyl-N-[(2-hydroxyphenyl)phenylmethyl]pentanamide
(3hb)
1
and 758. H NMR (300 MHz, CDCl3) δ: 1.71 (d, 3H, J =
7.3 Hz), 4.50 (s, 2H), 6.03 (q, 1H, J = 7.3 Hz), 6.60–7.40
(m, 14H), and 9.50 (bs, 1H). 13C NMR (75 MHz, CDCl3) δ:
17.9, 27.1, 49.4, 117.7, 119.6, 125.3, 126.9, 127.0, 127.2,
127.4, 127.8, 128.5, 128.5, 128.7, 129.9, 130.1, 156.1, and
175.4. Anal. calcd. (%) for C22H21NO2, MW 331.41: C
79.73, H 6.39, N, 4.23; found: C 79.48, H 5.58, N 4.32.
Oil. IR νmax (liquid film) (cm–1): 3142, 2956, 1626, 1487,
1454, 1229, and 761. 1H NMR (300 MHz, CDCl3) δ: 0.85 (t,
3H, J = 7.3 Hz), 1.22–1.38 (m, 2H), 1.53–1.75 (m, 2H),
2.22–2.38 (m, 1H), 2.42–2.56 (m, 1H), 4.57 (d, 1H, J =
16.9 Hz), 4.84 (d, 1H, J = 16.9 Hz), 6.65–7.40 (m, 15H),
and 8.90 (bs, 1H). 13C NMR (75 MHz, CDCl3) δ: 14.0, 22.7,
27.6, 34.09, 50.5, 58.0, 118.1, 119.9, 124.3, 126.2, 127.4,
127.8, 128.2, 128.7, 129.0, 130.0, 130.4, 136.9, 137.8,
156.7, and 177.5. Anal. calcd. (%) for C25H27NO2, MW
373.487: C 80.40, H 7.29, N 3.75; found: C 80.18, H 7.43,
N 3.57.
N-Benzyl-N-[1-(2-hydroxyphenyl)ethyl]but-3-enamide (3be)
Oil. IR νmax (liquid film) (cm–1): 3138, 2966, 1630, 1484,
1
1445, 1223, and 758. H NMR (300 MHz, CDCl3) δ: 1.49
(d, 3H, J = 7.1 Hz), 2.90–3.20 (m, 2H), 4.47 (s, 2H), 4.96
(d, 1H, J = 17.2 Hz), 5.11 (d, 1H, J = 9.9 Hz), 5.77–6.03 (m,
1H), 6.12 (q, 1H, J = 7.1), 6.80–7.40 (m, 9H), and 9.10 (bs,
1H). 13C NMR (75 MHz, CDCl3) δ: 17.4, 39.3, 46.8, 47.6,
117.8, 118.5, 119.7, 125.4, 125.9, 126.9, 127.8, 129.1,
129.9, 131.0, 137.4, 155.8, and 175.2. Anal. calcd. (%) for
C19H21NO2, MW 295.38: C 77.26, H 7.17, N 4.74; found: C
79.43, H 7.28, N 4.51.
N-Benzyl-N-[(2-hydroxyphenyl)phenylmethyl]isobutyra-
mide (3hc)
White crystals; mp 166–167 °C (n-hexane/CH2Cl2). IR
νmax (Nujol) (cm–1): 3138, 2966, 1630, 1484, 1445, 1223,
1
and 758. H NMR (300 MHz, CDCl3) δ: 0.92 (d, 3H, J =
6.1 Hz), 1.26 (d, 3H, J = 7.0 Hz), 2.67–2.82 (m, 1H), 4.61
© 2004 NRC Canada

Cimarelli et al.
1321
4. (a) E. Merck. A.-G. Neth. Appl. 297 368, 1965; Chem. Abstr.
64, 3563a (1966); (b) E. Merck. A.-G. Neth. Appl. 6 511 478,
1966; Chem. Abstr. 65, 10 596f (1966).
5. J. Sanz-Asensio, M. Plaza-Medina, M.T. Martinez-Soria, and
M. Perez-Clavijo. J. Chromatogr. A 840, 235 (1999).
6. E. Merck. A.-G. French Patent M2933, 1964; Chem. Abstr. 62,
14 689g (1965).
(d, 1H, J = 17.5 Hz), 4.84 (d, 1H, J = 17.5 Hz), 6.60–7.40
(m, 15H), and 9.00 (bs, 1H). 13C NMR (75 MHz, CDCl3) δ:
18.9, 20.8, 32.3, 50.2, 57.5, 118.2, 119.9, 124.0, 126.0,
127.4, 127.7, 128.6, 128.7, 129.3, 130.1, 130.3, 137.4, 137.7,
157.0, and 182.0. Anal. calcd. (%) for C24H25NO2, MW
359.46: C 80.19, H 7.01, N 3.90; found: C 79.97, H 7.23, N
3.69.
7. R.E. Strube and F.A. Mackellar. Recl. Trav. Chim. Pays–Bas,
83, 1191 (1964).
(l)-( )-N-[(2-Hydroxyphenyl)phenylmethyl]-N-(1-
8. N.M. Yousef, A.F.M. Fahmy, M.S. Amine, F.A. Gad, and H.H.
Sayed. Indian. J. Heterocycl. Chem. 7, 119 (1997).
9. (a) J. Mindl, O. Hrabik, V. Sterba, and J. Kavalek. Collect.
Czech. Chem. Commun. 65, 1262 (2000). (b) A.S. Girgis.
Pharmazie, 55, 426 (2000). (c) Jpn. Kokai Tokkyo Koho, Japa-
nese Patent 60 081 182, 1985; Chem. Abstr. 103, 215 305
(1985).
10. N. Latif, N. Mishriky, and F.M. Assad. Aust. J. Chem. 35,
1037 (1982).
11. Y. Wang, X. Li, and K. Ding. Tetrahedron: Asymmetry, 13,
1291 (2002).
phenylethyl)pentanamide ((l)-3ib)
Oil. IR νmax (liquid film) (cm–1): 3140, 2961, 1626, 1486,
1451, 1229, and 761. 1H NMR (300 MHz, CDCl3) δ: 0.96 (t,
3H, J = 7.3 Hz), 1.38–1.60 (m, 2H), 1.65–1.87 (m, 2H), 1.81
(d, 3H, J = 7.0 Hz), 2.68 (t, 2H, J = 7.5 Hz), 5.50 (q, 1H, J =
7.0 Hz), 5.60 (m, 1H) 6.30–7.40 (m, 14H), and 9.85 (bs,
1H). 13C NMR (75 MHz, CDCl3) δ: 14.0, 18.0, 22.8, 27.7,
35.2, 56.7, 62.2, 118.9, 124.6, 126.2, 126.5, 126.9, 128.0,
128.4, 128.8, 129.4, 129.6, 133.0, 138.5, 139.36, 156.3, and
174.8. Anal. calcd. (%) for C26H29NO2, MW 387.514: C
80.59, H 7.54, N 3.61; found: C 80.32, H 7.76, N 3.48
12. K. Ikeda, T. Morimoto, and M. Sekyia. Chem. Pharm. Bull.
1178 (1980).
13. (a) G. Palmieri. Eur. J. Org. Chem. 805 (1999). (b) C.
Cimarelli, G. Palmieri, and E. Volpini. Tetrahedron, 57, 6089
(2001). (c) C. Cimarelli, G. Palmieri, and E. Volpini. Tetrahe-
dron, 57, 6809 (2001). (d) C. Cimarelli, G. Palmieri, and E.
Volpini. J. Org. Chem. 68, 1200 (2003).
N-Benzyl-[(2-hydroxynaphthalen-1-yl)phenylmethyl]-
pentanamide (6ab)
Oil. IR νmax (liquid film) (cm–1): 3138, 2966, 1630, 1484,
1445, 1223, and 758. 1H NMR (300 MHz, CDCl3) δ: 0.89 (t,
3H, J = 7.1 Hz), 1.26–1.43 (m, 2H), 1.60–1.78 (m, 2H),
2.38–2.67 (m, 2H), 4.54 (d, 1H, J = 16.8 Hz), 4.91 (d, 1H,
J = 16.8), 6.90–7.70 (m, 17H), and 8.63 (bs, 1H). 13C NMR
(75 MHz, CDCl3) δ: 14.1, 22.7, 27.7, 34.3, 51.7, 57.4, 114.4,
120.6, 122.3, 123.0, 126.5, 126.6, 127.0, 127.5, 127.6,
128.6, 129.1, 129.1, 129.3, 131.3, 134.3, 136.4, 137.9,
155.2, and 176.2. Anal. calcd. (%) for C29H29NO2, MW
423.55: C 82.24, H 6.90, N 3.31; found: C 79.47, H 5.78, N
3.54.
14. (a) C. Cimarelli, A. Mazzanti, G. Palmieri, and E. Volpini. J.
Org. Chem. 66, 4759 (2001). (b) C. Cimarelli, G. Palmieri,
and E. Volpini. Tetrahedron: Asymmetry, 13, 2417 (2002).
15. (a) G.B. Barlin, S.J. Ireland, T.M.T. Nguyen, B. Kotecka, and
K.H. Rieckmann. Aust. J. Chem. 47, 1143 (1994). (b) G.B.
Barlin, S.J. Ireland, T.M.T. Nguyen, B. Kotecka, and K.H.
Rieckmann. Aust. J. Chem. 47, 1553 (1994). (c) L. Jurd, R.L.
Fye, and J. Morgan, Jr. J. Agric. Food Chem. 27, 1007 (1979).
(d) P.A. Langley, M.A. Trewern, and L. Jurd. Bull. Entomol.
Res. 72, 473 (1982). (e) L. Jurd. J. Heterocycl. Chem. 22, 993
(1985). (f) V.N. Komissarov, L.Y. Ukhin, V.A. Kharlanov, V.A.
Lokshin, and E.Y. Bulgarevich. Bull. Acad. Sci. USSR, Div.
Chem. Sci. 41, 1875 (1992).
Acknowledgement
16. D.J. Berrisford, C. Bolm, and K.B. Sharpless. Angew. Chem.
Financial support from the Ministero del l’Università e
della Ricerca Scientifica e Tecnologica, Rome and the Uni-
versity of Camerino (National Project “Stereoselezione in
Sintesi Organica. Metodologie ed applicazioni”) is gratefully
acknowledged.
Int. Ed. Engl. 34, 1059 (1995).
17. (a) G. Palmieri. Tetrahedron: Asymmetry, 11, 3361 (2000).
(b) C. Cardellicchio, G. Ciccarella, F. Naso, F. Perna, and P.
Tortorella. Tetrahedron, 55, 14685 (1999).
18. J.R. Geigy Akt.-Ges. British Patent 811 130, 1959; Chem.
Abstr. 54, 2270e (1960).
19. H. Ohtake, Y. Imada, and S. Murahashi. J. Org. Chem. 64,
3790 (1999).
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