Synthesis of benzomacrolactam by 12-endo selective aryl radical cyclization of N-(4-allyloxybutyl)-2-iodobenzamide

Article abstract of DOI:10.1081/SCC-120015778

Regioselective 12-endo aryl radical cyclization of N-(4-allyloxybutyl)-2-iodobenzamide (7) with tri-n-butyltin hydride provided benzomacrolactam 15. The structure of 15 is supported by ¹H and ¹³CNMR spectroscopy and by DEPT, COSY, CO

Full text of DOI:10.1081/SCC-120015778

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Synthesis of Benzomacrolactam by 12- endo Selective
Aryl Radical Cyclization of N -(4-Allyloxybutyl)-2-
iodobenzamide
André Augusto Gomes Faraco a , Maria Auxiliadôra F. Prado b , Ricardo J. Alves b , José D.
Souza Filho a , Rosemeire Brondi Alves a & Renata F. Prado Faraco b
a Departamento de Química , Instituto de Ciências Exatas , Universidade Federal de Minas
Gerais , Avenida Antônio Carlos 6627, Belo Horizonte, Brazil
b Departamento do Produtos Farmacêuticos , Faculdade de Farmácia , Universidade Federal
de Minas Gerais , Avenida Olegário Maciel 2360, Belo Horizonte, Brazil
Published online: 17 Aug 2006.
To cite this article: André Augusto Gomes Faraco , Maria Auxiliadôra F. Prado , Ricardo J. Alves , José D. Souza Filho ,
Rosemeire Brondi Alves & Renata F. Prado Faraco (2003) Synthesis of Benzomacrolactam by 12- endo Selective Aryl Radical
Cyclization of N -(4-Allyloxybutyl)-2-iodobenzamide, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:3, 463-474, DOI: 10.1081/SCC-120015778
To link to this article: http://dx.doi.org/10.1081/SCC-120015778
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 3, pp. 463–474, 2003
Synthesis of Benzomacrolactam
by 12-endo Selective Aryl Radical Cyclization
of N-(4-Allyloxybutyl)-2-iodobenzamide
Andre Augusto Gomes Faraco,1 Maria Auxiliadora F. Prado,2,
*
Ricardo J. Alves,2 Jose D. Souza Filho,1
Rosemeire Brondi Alves,1 and Renata F. Prado Faraco2
1Departamento de Quımica, Instituto de Ciencias Exatas,
Universidade Federal de Minas Gerais,
Avenida Antonio Carlos 6627, Belo Horizonte, Brazil
2Departamento do Produtos Farmaceuticos, Faculdade de
Farmacia, Universidade Federal de Minas Gerais,
Avenida Olegario Maciel 2360, Belo Horizonte, Brazil
ABSTRACT
Regioselective 12-endo aryl radical cyclization of N-(4-allyloxybutyl)-
2-iodobenzamide (7) with tri-n-butyltin hydride provided benzo-
macrolactam 15. The structure of 15 is supported by 1H and 13C NMR
spectroscopy and by DEPT, COSY, COSYLR and HMQC experiments.
*Correspondence: Maria Auxiliadora F. Prado, Departamento do Produtos
Farmaceuticos, Faculdade de Farmacia, Universidade Federal de Minas Gerais,
Avenida Olegario Maciel 2360, Belo Horizonte-30.180-112, Brazil; E-mail:
doraprad@dedalus.kc.ufmg.br.
463
DOI: 10.1081/SCC-120015778
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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464
Faraco et al.
INTRODUCTION
Bu3SnH-mediated aryl radical cyclizations are now widely used in
organic synthesis for the construction of fused aromatic compounds.[1]
There are several examples of fused aromatic compounds obtained by
Bu3SnH-mediated aryl radical cyclization from ortho-halogen compounds
bearing a carbon–carbon double bound in the side chain. Most of them
have five- or six-membered rings fused to a phenyl group.[1–9] Some of
these compounds are g- or d-lactams fused to the aromatic ring.[1–6] To
the best of our knowledge, until 1999 there were only two reports of
mediated aryl radical cyclization to give fused aromatic compounds in
which the rings have more than six members[8,9] and there were no benzo-
lactams with lactam rings larger than six members obtained by the same
method. This fact can be attributed to the occurrence of intramolecular
radical translocation by 1,5-hydrogen-atomtransfer. In the ortho-halogen-
benzamides bearing a hydrogen in the saturated carbon at the 5-position
relative to the halogen atom, the generation of aryl radical is followed by
intramolecular hydrogen-atom transfer to the aryl group. An amidoyl
radical is formed and it undergoes a variety of new radical addition and
cyclization reactions.[10]
Despite our knowledge of 1,5-hydrogen-atomtransfer, we decided to
investigate the Bu3SnH-mediated aryl radical cyclization reaction of
methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(2-iodobenzoylamino)-a-D-
glucopyranoside 1. Only the benzomacrolactam 2, resulting from11- endo
aryl radical cyclization, and the hydrogenolysis product were obtained in
40% and 42% yield, respectively.[11]
We also applied this methodology to create benzomacrolactams 3
and/or 4 by 11-endo and/or 10-exo cyclization from N-(3-allyloxy-
propyl)-2-iodobenzamide (5) to examine if the conformational restraints

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Benzomacrolactam
465
of 1 imposed by the carbohydrate unit aids the cyclization reaction and
affects the cyclization mode (endo or exo). We also obtained the benzo-
macrolactam resulting from 11-endo aryl radical cyclization 3 and the
hydrogenolysis product in 14% and 15% yield, respectively.[11]
Wefoundthatthe11-endocyclizationmodeispreferredovera10-exoring
closure in Bu3SnH-induced aryl radical cyclization of o-iodobenzamides
bearing an allyloxy group in the side chain. The lactam:hydrogenolysis
product ratio frombenzamide
1 (1:1) and fromsubstrate 5 (1.5:8.5)
suggest that the conformational restraints imposed by the sugar unit
in the carbohydrate aryl radical precursor favored cyclization.[11]
This investigation shows the potential of aryl radical macrocyclization
from o-iodobenzamides bearing a hydrogen atom on the saturated
carbon at position 5 relative to the halogen atomand an allyloxy
group at the side chain in the synthesis of condensed lactams incorporat-
ing large rings.[11]
We applied the Bu3SnH-mediated radical cyclization reaction to
synthesize benzolactams by 10- and 12-endo and/or 9- and 11-exo cycliza-
tion from N-(2-allyloxyethyl)-2-iodobenzamide (6) and N-(4-allyl-
oxybutyl)-2-iodobenzamide (7).

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466
Faraco et al.
RESULTS AND DISCUSSION
The 2-iodobenzamide 6 was readily prepared by the condensation of
ethanolamine (8) with 2-iodobenzoyl chloride, followed by O-alkylation of
the resulting N-(2-hydroxyethyl)-2-iodobenzamide (9) with allyl bromide
(Sch. 1).
Benzamide 7 was obtained from4-chlorobutan-1-ol ( 10) in four con-
ventional synthetic steps. Treatment of the starting material with
NaN3 in DMF gave the 4-azide derivative 11, which was treated
with allyl bromide in the presence of NaH in DMF to give O-allyl com-
pound 12. Selective reduction of the azido group using lithium
aluminum hydride afforded the desired amino compound 13. The
o-iodobenzamide 7 was obtained by reaction of 13 with 2-iodobenzoyl
chloride (Sch. 2).
Consideration of the competing reactions available to the radicals
involved in the cyclization reaction suggested that the formation of the
desired cyclized products should be improved by conducting the experi-
ment with very low concentrations of both iodobenzamines and Bu3SnH
and slow addition of Bu3SnH/AIBN to the benzene solution, thus
decreasing the intermolecular reactions and the rate of hydrogen
[6,12,13]
atomtransfer to uncyclized radicals.
Thus, a mixture of
Bu3SnH (1.5 equiv.) and AIBN (catalytic amount) in nitrogen-saturated
anhydrous benzene was added over 1 h to the solutions of iodobenza-
mides 6 and 7 in nitrogen-saturated anhydrous benzene maintained
at 80ꢀC to give a 0.018 mol Lꢁ1 reaction mixture in Bu3SnH. The reac-
tion mixtures were heated under reflux for further 1 h. The solvent
was removed and the residues were submitted to column chromatog-
raphy on silica gel. Only the hydrogenolysis product 14 was isolated
in 76% yield from 6. On the other hand, iodobenzamide 7 gave the
macrolactam 15 resulting from12- endo aryl radical cyclization and the
hydrogenolysis compound 16 in 19% and 33% yields, respectively
(Sch. 3).
Scheme 1. Reagents, conditions and yields: i, 1.1 equiv. 2-iodobenzoyl chloride,
1.1 equiv. triethylamine, ethyl ether, r.t., 60%; ii, 0.5 equiv. Bu4NBr, 5% aqu.
NaOH, 2 equiv. allyl bromide, ethyl ether, r.t., 59%.

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Benzomacrolactam
467
Scheme 2. Reagents, conditions and yields: i, 3 equiv. NaN3, DMF, r.t., 50%; ii,
0.5 equiv. Bu4NHSO4, 50% aqueous NaOH, 3 equiv. allyl bromide, ethyl ether,
r.t., 61%; iii, 2 equiv. LiAlH4, ethyl ether, r.t., quantitative; iv, 1.2 equiv. 2-iodo-
benzoyl chloride, 1.2 equiv. triethylamine, ethyl ether, r.t., 42% from 12.
1
The structures of the compounds obtained are supported by H,
13C, and DEPT NMR spectra. The spectra of 6, 7, 9, 11, 12, and 15
indicate the purity of these compounds. On the other hand, an inspec-
1
tion of the H NMR spectra of 14 and 16 allows the visualization of
signals relative to the butyl group of tri n-butyltin compounds. The
structure of lactam 15 is also confirmed unequivocally by the COSY,
COSYLR, and HMQC experiments and its elemental analysis is almost
acceptable (Found: C, 70.5; H, 7.7; N, 5.8. Calc. for C14H19NO2: C,
72.1; H, 8.2; N, 6.0%). The errors can be attributed to the presence of
very small quantities of tri n-butyltin compounds. Attempts to obtain
compounds 14, 15, and 16 with suitable purity were not successful
in view of the well-known poor separation of the products fromtin
residues.[14] The smaller purity of 14 and 16, which are oils, compared
to those of 15, a white solid, can be attributed to the greater difficulty
of purifying syrups.
The selected 13C NMR data for precursors 6 and 7, hydrogenolysis
products 14 and 16 and lactam 15 are listed in the Table 1.
CONCLUSION
We found that the Bu3SnH-induced aryl radical cyclization of ortho-
iodobenzamides 6 provided exclusively the hydrogenolysis product 14.
On the other hand, the precursor 7 afforded the hydrogenolysis product
16 and lactam 15, resulting from12- endo aryl radical cyclization. These

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468
Faraco et al.
Scheme 3. Reagents, conditions, and yields: i, 1.5 equiv. Bu3SnH, AIBN
(catalytic amount), benzene, reflux, 14 76%, 15 19%, 16 33%.
results along with the previous data[11] show that the 11- and 12-endo
cyclization modes are preferred over a 10- and 11-exo ring closure. This
conclusion is in agreement with the guideline for radical macrocyclization
that ‘‘endo cyclization modes are favored’’[15] and with other literature
macrocyclization data.[8,9] Fromthese studies we conclude that the 11-
and 12-endo carbocyclizations are favored over the 10-endo cyclization
mode. In fact, to the best of our knowledge, there are no cyclic com-
pounds described in the literature in which the carbocyclic rings have
10 members formed by Bu3SnH-mediated radical reaction.
EXPERIMENTAL
General Procedures
All melting points were determined on a Kofler Sybron apparatus
and are uncorrected. Nuclear magnetic resonance spectra were measured
in deuteriochloroformwith TMS as the internal standard with a Bruker
Avance-200 instrument. Chemical shifts are given in ꢀ scale. J values are

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Benzomacrolactam
Table 1. 13C NMR (CDCl3, 50 MHz) data for 6, 7,
14, 15, and 16.
469
Compound
Carbon
ꢀ (ppm)
142.10
92.31
6
1-C
2-C
9-C
10-C
11-C
71.84 or 68.27
134.21
117.30
14
1-C
2-C
134.22
One of 3 signals between
131.14 and 126.71
71.12 or 68.47
134.11
9-C
10-C
11-C
117.12
7
1-C
2-C
142.30
92.31
11-C
12-C
13-C
71.72 or 69.68
134.39
116.94
15
16
1-C, 2-C
11-C
12-C
138.12, 137.20
66.88
29.82
13-C
27.79
1-C
2-C
134.68
One of 3 signals between
131.14 and 126.78
71.72 or 69.79
134.61
11-C
12-C
13-C
116.80
given in Hz. Column chromatography was performed with silica gel 60,
70–230 mesh (Merck). The term ‘‘standard work-up’’ means that the
organic layer was washed with water, dried over anhydrous sodium
sulfate, filtered and the solvent was removed under reduced pressure.
N-(2-Hydroxyethyl)-2-iodobenzamide 9[16]: To a solution of 2-amino-
ethanol 8 (1 mL, 1.01 g, 16.6 mmol) and triethylamine (2.6 mL, 1.92 g,
19 mmol) in anhydrous ethyl ether (70 mL) was added to a solution of
2-iodobenzoyl chloride (5.06 g, 19 mmol) in ethyl ether (30 mL). The mix-
ture was stirred for 2 h at roomtemperature. Water was added, the organic

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470
Faraco et al.
layer was separated and the aqueous layer was extracted with CH2Cl2.
Standard work-up gave a residue which was submitted to column chro-
matography. The iodobenzamide 9 (2.91 g, 10 mmol, 60%), eluted with
ethyl acetate, was obtained as a white solid; m.p. 90.6–91.9ꢀC; ꢀH
(200 MHz, CDCl3) 7.80 (1H, d, J3,4 7.9, 3-H), 7.39–7.27 (2H, m, Ph),
7.05 (1H, ddd, Jortho 7.9 Jortho 5.5 Jmeta 3.7, 5-H or 4-H), 6.43 (1H,
br s, NH), 3.82 (2H, t, J7,8 5.3, 8-H), 3.48 (2H, q, J7,NH ¼ J7,8 5.3, 7-H),
2.80 (1H, br s, OH); ꢀC (50 MHz, CDCl3) 170.23 (C¼O), 141.90 (1-C),
139.80 (3-C), 131.11, 128.09 (Ar), 92.42 (2-C), 61.74 (8-C), 42.68 (7-C).
N-(2-Allyloxyethyl)-2-iodobenzamide 6[17]: To a solution of iodoben-
zamide 9 (1.00 g, 3.47 mmol) in ethyl ether (30 mL) were added, under
magnetic stirring, 5% aqueous NaOH (7 mL) and Bu4NBr (0.56 g,
1.72 mmol), as a phase transfer catalyst. The mixture was stirred for
30 min. Allyl bromide (0.6 mL, 0.85 g, 7 mmol) was added and the mixture
was stirred for 21 h. The organic layer was separated and the aqueous layer
was extracted with ethyl ether. Standard work-up gave a residue which was
submitted to column chromatography. The allyloxyiodobenzamide 6
(0.67 g, 2.01 mmol, 59%), eluted with hexane–ethyl acetate 7:3, was
obtained as a syrup; ꢀH (200 MHz, CDCl3) 7.82 (1H, d, J3,4 7.9, 3-H),
7.39–7.32 (2H, m, Ph), 7.02 (1H, m, Ph), 6.32 (1H, br s, NH), 5.88 (1H,
0
dtd, J10,11 17.3, J10,11 10.3, J10,9 5.6, 10-H), 5.21 (1H, dq, J10,11 17.3,
0
Jgem ¼ J11,9 1.6, 11-H), 5.12 (1H, dq, J11 ,10 10.3, Jgem ¼ J11 ,9 1.6, 110-H),
0
0
4.02 (2H, dt, J9,10 5.6, J9,11 ¼ J9,11 1.6, 9-H), 3.71–3.59 (4H, m, 7-H and
8-H); ꢀC (50 MHz, CDCl3) 169.23 (C¼O), 142.10 (1-C), 139.62 (3-C),
134.21 (10-C), 130.88, 128.27, 128.04 (Ar), 117.30 (11-C), 92.31 (2-C),
71.84, 68.27 (8-C and 9-C), 39.57 (7-C).
Radical cyclization of compound 6[11,13]: To a stirred, boiling solution
of compound 6 (0.331 g, 1 mmol) in nitrogen-saturated benzene (70 mL)
was added a solution of Bu3SnH (0.42 mL, 0.44 g, 1.5 mmol) and AIBN
(0.01 g) in nitrogen-saturated benzene (12 mL) via an addition funnel
during 1 h. The reaction mixture was heated under reflux and a nitrogen
atmosphere for further 1 h. Subsequent solvent removal and column chro-
matography gave the uncyclized product 14 (0.16 g, 0.76 mmol, 76%),
eluted with hexane–ethyl acetate 8:2. The hydrogenolysis product 14 was
obtained as an oil; ꢀH (200 MHz, CDCl3) 7.76 (2H, dd, J2,3 7.2, J2,4 1.3, 2-
H), 7.40–7.22 (3H, m, Ph), 6.81 (1H, br s, NH), 5.83 (1H, dtd, J10,11 17.3,
0
J10,11 10.3, J10,9 5.6, 10-H), 5.20 (1H, dq, J11,10 17.3, Jgem ¼ J11,9 1.6, 11-H),
5.00 (1H, dq, J11 ,10 10.3, Jgem ¼ J11 ,9 1.6, 110-H), 3.81 (2H, dt, J9,10 5.6
0
0
0
J9,11 ¼ J9,11 1.6, 9-H), 3.59–3.38 (4H, m, 7-H and 8-H); ꢀC (50 MHz,
CDCl3) 167.39 (C¼O), 134.22 (1-C), 134.11 (10-C), 131.14, 128.19,
126.71 (Ar), 117.12 (11-C), 71.72, 68.47 (8-C and 9-C), 39.57 (7-C).

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Benzomacrolactam
471
4-Azidobutan-1-ol 11[18]: To a solution of 4-chlorobutan-1-ol 10
(4.6 mL, 5 g, 46 mmol) in DMF (30 mL) was added NaN3 (9 g, 130 mmol).
The solution was stirred for 30 h at roomtemperature. Distillation of
DMF under reduced pressure, addition of water, extraction with CH2Cl2,
and standard work-up gave a residue which was submitted to column
chromatography. Elution with hexane–ethyl acetate 7:3 gave the azide
derivative 11 (2.3 g, 23 mmol, 50%) as an oil; ꢀH (200 MHz, CDCl3) 3.59
(2H, t, J 6.0, 1-H or 4-H), 3.30 (2H, t, J 6.0, 1-H or 4-H), 2.11 (1H, s, OH),
1.72–1.59 (4H, mm, 2-H and 3-H); ꢀC (50 MHz, CDCl3) 61.91 (1-C), 51.19
(4-C), 29.63, 25.22 (2-C and 3-C).
3-(4-Azidobutoxy)prop-1-ene 12[17]: To a solution of 11 (0.59 g,
4.6 mmol) in ethyl ether (12 mL) were added, under magnetic stirring,
50% aqueous NaOH (9 mL) and Bu4NHSO4 (0.88 g, 2.5 mmol), as a
phase transfer catalyst. The mixture was stirred for 30 min. Allyl bromide
(1.12 mL, 1.5 g, 13 mmol) was added and the mixture was stirred for 38 h.
The organic layer was separated and the aqueous layer was extracted with
ethyl ether. Standard work-up gave a residue which was submitted to
column chromatography. Product 12 (0.43 g, 2.8 mmol, 61%), eluted
with hexane–ethyl acetate 95:5, was obtained as an oil; ꢀH (200 MHz,
0
CDCl3) 5.92 (1H, dtd, J6,7 17.3, J6,7 10.3, J6,5 5.5, 6-H), 5.21 (1H, dq,
0
0
J7,6 17.3, Jgem ¼ J7,5 1.6, 7-H), 5.10 (1H, dq, J7 ,6 10.3, Jgem ¼ J7 ,5 1.6,
70-H), 3.9 (2H, td, J5,6 5.5 J5,7 ¼ J5,7 1.6, 5-H), 3.49–3.41 (2H, m, 1-H or
0
4-H), 3.31 (2H, t, J 6.4, 1-H or 4-H), 1.71–1.59 (4H, m, 2-H and 3-H); ꢀC
(50 MHz, CDCl3) 134.80 (6-C), 116.80 (7-C), 71.84, 69.48 (1-C and 5-C),
51.22 (4-C), 26.83, 25.81 (2-C and 3-C).
4-(Allyloxy)butan-1-amine 13[19]: To a suspension of lithiumalumi-
num hydride (0.19 g, 5 mmol) in anhydrous ethyl ether (5 mL) was added
a solution of 3-(4-azidobutoxy)prop-1-ene 12 (0.37 g, 2.4 mmol) in ethyl
ether (5 mL). The mixture was stirred for 8 h at room temperature. Water
(3 mL) and 5% aqueous NaOH (0.5 mL) were added to it. The organic
layer was separated and the aqueous layer was extracted with ethyl ether.
Standard work-up gave the 4-(allyloxy)butan-1-amine 13, which was not
submitted to purification.
N-(4-Allyloxybutyl)-2-iodobenzamide 7[16]: To a solution of 4-
(allyloxy)butan-1-amine 13, obtained as described above, and triethyla-
mine (0.4 mL, 0.30 g, 2.9 mmol) in anhydrous ethyl ether (10 mL) was
added a solution of 2-iodobenzoyl chloride (0.77 g, 2.9 mmol) in ethyl
ether (5 mL). The mixture was stirred for 1 h. Water was added, the organic
layer was separated and the aqueous layer was extracted with ethyl ether.
Standard work-up gave a residue which was submitted to column chro-
matography. The iodobenzamide 7 (0.36 g, 1 mmol, 42% from 13), eluted

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472
Faraco et al.
with hexane–ethyl acetate 1:1, was obtained as an oil; ꢀH (200 MHz,
CDCl3) 7.81 (1H, d, J3,4 7.8, 3-H), 7.39–7.31 (2H, m, Ph), 7.10–7.03
0
(1H, m, Ph), 6.38 (1H, br s, NH), 5.82 (1H, dtd, J12,13 17.3, J12,13 10.3,
J12,11 5.6, 12-H), 5.21 (1H, dq, J13,12 17.3, Jgem ¼ J13,11 1.6, 13-H), 5.12 (1H,
dq, J13 12 10.3, Jgem ¼ J13 ,11 1.6, 130-H), 3.91 (2H, dt, J11,12 5.6,
0
0
0
J11,13 ¼ J11,13 1.6, 11-H), 3.49–3.28 (4H, m, 7-H and 10-H), 1.70–1.59
(4H, m, 8-H and 9-H); ꢀC (50 MHz, CDCl3) 169.53 (C¼O), 142.30 (1-C),
139.52 (3-C), 134.39 (12-C), 130.68, 128.02, 127.91 (Ar), 116.94 (13-C),
92.31 (2-C), 71.72, 69.68 (10-C and 11-C), 39.71 (7-C), 27.11, 26.08 (8-C
and 9-C); (Found: C, 46.4; H, 5.1; N, 3.7. Calc. for C14H18INO2: C, 46.8;
H, 5.1; N, 3.9%).
Radical cyclization of compound 7[11,13]: By treating iodobenzamide 7
(0.359 g, 1 mmol) as described above for 6 gave successively the uncyclized
product 16 (0.077 g, 0.33 mmol, 33%) and macrolactam 15 (0.044 g,
0.19 mmol, 19%), which were eluted with hexane–ethyl acetate 8:2 and
6:4, respectively. The hydrogenolysis product 16 was obtained as an oil;
ꢀH (200 MHz, CDCl3) 7.78 (2H, dd, J2,3 7.2, J2,4 1.6, 2-H), 7.48–7.29 (3H,
m, Ph), 6.71 (1H, br s, NH), 5.90 (1H, dtd, J12,13 17.3, J12,13 10.3, J12,11 5.6,
0
0
12-H), 5.20 (1H, dq, J13,12 17.3, Jgem ¼ J13,11 1.6, 13-H), 5.15 (1H, dq, J13 ,12
10.3, Jgem ¼ J13 ,11 1.6, 130-H), 3.88 (2H, dt, J11,12 5.6, J11,13 ¼ J11,13 1.6,
11-H), 3.49–3.28 (4H, m, 7-H and 10-H), 1.71–1.62 (4H, m, 8-H and 9-H);
ꢀC (50 MHz, CDCl3) 167.39 (C¼O), 134.68 (1-C), 134.61 (12-C), 131.14,
128.30, 126.78 (Ar), 116.80 (13-C), 71.72, 69.79 (10-C and 11-C), 39.60
(7-C), 27.0, 26.28 (8-C and 9-C); (Found: C, 65.9; H, 7.5; N, 6.2. Calc. for
C14H19NO2: C, 72.1; H, 8.2; N, 60%). The macrolactam 15 was obtained
as a white solid; m.p. 151–154ꢀC; ꢀH (200 MHz, CDCl3) 7.60 (1H, br s,
NH), 7.50 (1H, d, J6,5 7.6, 6-H), 7.40–7.30 (1H, m, 4-H), 7.28–7.22 (2H, m,
3-H and 5-H), 3.50 (2H, q, J7,8 ¼ J7,NH 5.5, 7-H), 3.42 (2H, t, J10,9 4.5,
10-H), 3.30 (2H, t, J11,12 5.4, 11-H), 2.92 (2H, t, J13,12 6.3, 13-H), 2.00 (2H,
tt, J13,12 6.3, J12,11 5.4, 12-H), 1.80–1.70 (4H, m, 8-H and 9-H); ꢀC (50 MHz,
CDCl3) 169.11 (C¼O), 138.12, 137.20 (1-C and 2-C), 130.08, 129.71,
128.52, 126.08 (Ar), 69.58 (10-C), 66.88 (11-C), 40.12 (7-C), 29.82
(12-C), 29.13 (8-C or 9-C), 27.79 (13-C), 27.51 (8-C or 9-C); (Found: C,
70.5; H, 7.7; N, 5.8. Calc. for C14H19NO2: C, 72.1; H, 8.2; N, 6.0%).
0
0
ACKNOWLEDGMENTS
A. G. Faraco, R. F. P. Faraco, M. A. F. Prado, and R. B. Alves
thank Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico

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Benzomacrolactam
473
(CNPq) for fellowships. The authors thank Fundacao de Amparo a
Pesquisa do Estado de Minas Gerais (FAPEMIG) for financial support.
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Received in the USA February 22, 2002