Structural determination of ε-lactams by 1H and 13CNMR

Article abstract of DOI:10.1002/mrc.2504

The thermodynamic products (ε-lactams) of the degradation of ten different spirocyclic oxaziridines were analyzed by ¹H and ¹³C NMR spectroscopy. The preferred conformations were determined by examining the homonuclear spin-spin coup

Full text of DOI:10.1002/mrc.2504

Research Article
Received: 31 March 2009
Revised: 17 July 2009
Accepted: 26 July 2009
Published online in Wiley Interscience: 31 August 2009
(www.interscience.com) DOI 10.1002/mrc.2504
Structural determination of ε-lactams by 1H
and 13C NMR
a
b∗
´
´
Ruben Montalvo-Gonzalez and Armando Ariza-Castolo
The thermodynamic products (ε-lactams) of the degradation of ten different spirocyclic oxaziridines were analyzed by 1H and
13C NMR spectroscopy. The preferred conformations were determined by examining the homonuclear spin–spin coupling
constant and the chemical shift effects of the N-substituent and the alkyl group of the aliphatic ring on 1H and 13C NMR spectra.
c
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: NMR; 1H; 13C; conformation; e-lactams
Introduction
azepinones 1a, 1b, 1d,1e, 2a, 2b, 2d and 2e and that of the
aliphatic ring from chemical shifts and three-bond proton–proton
coupling constants.
A number of ε-lactams are of commercial interest,[1] and their
syntheses have been reported.[2] The main focus of these reports
was the mechanism of ε-lactam formation and the regioselectivity
of the reaction. However, relatively little is known regarding the
structures and preferred conformations of these compounds.
Knowledge of the substituent effect provoked by different
functional groups is important in determining the preferred
conformation,[3] the relative and absolute configuration[4] as well
as the reactivity and stereoselectivity.[5] Here, we describe the
structures and conformations of ten different azepinones, which
were obtained as thermodynamic compounds from the photo-
chemical rearrangement of the corresponding spirooxaziridines
prepared by the oxidation of the C N double bond of exocyclic
ketimines.[6] We determined the preferred conformation of the
heterocyclic ring, the position of substituents attached to nitro-
gen and the alkyl group as well as the effects of groups attached
to the seven-membered ring atoms.
On the NMR time scale (at 20 ◦C), the chemical exchange
of the azepinones 1a and 2a due to ring inversion is faster
than the observed 1H frequency (300 MHz), as evidenced by the
chemical shifts of the protons attached to C3 and C7. Methyl or
t-butyl groups (1b–1g and 2b–2g) at the aliphatic ring prefer
the pseudoequatorial position. Azepinones 1d, 1e, 2d and 2e are
asymmetric and were obtained as racemic mixtures.
The rearrangement of oxaziridines obtained from the oxidation
ofketimines[6] synthesizedfrom3-or2-methylcyclohexanonewith
aniline or 3-aminopiridine were obtained as two pairs of isomers
with the chiral center at C3 or C7 [2-methylcyclohexanone deriva-
tives (1b, 1g, 2b and 2g)] or C4 or C6 [3-methylcyclohexanone
derivatives (1c, 1f, 2c and 2f)], respectively. The relative propor-
tions of the isomers were 10 : 1 for the 2-methylcyclohexanone
derivatives (1b and 1g or 2b and 1g) and 10 : 9 for the 3-
methylcyclohexanone derivatives (1c and 1f or 2c and 2f).
These ratios were similar to those observed in oxaziridines (to
be published). The orientation of the nitrogen insertion producing
seven-membered rings is similar to the behavior reported for the
photochemical rearrangement.[7]
The assignment of the aliphatic heterocyclic atoms was based
on the inductive effects and those of the N-substituents. To obtain
an unequivocal set of chemical shifts (Table 1) and proton–proton
coupling constants (Table 2), these quantities were determined
by simulation.[8]
The substituent effects of placing a methyl group at different
positions on the seven-membered ring, were determined by
examiningthe13CNMRspectralfeatures(Table 3), andtheanalysis
Mobile (R1 = H) and anchored (R1 = methyl or t-butyl)
compounds were used in the structural analyses. All compounds
had a seven-membered heterocyclic ring and phenyl (1a–1g) or
(3-pyridyl) groups (2a–2g) bound to the lactam nitrogen atom
(Fig. 1).
Results
The assignment of the 1H and 13C NMR spectra of the ε-lactams
is based on one- and two-dimensional NMR experiments. The
connectivity was established by homonuclear 1H–1H (COSY)
and heteronuclear 1H–13C (HETCOR) correlation spectroscopy.
Modulated coupling constant spectroscopy (APT, attached proton
test)wascarriedouttodifferentiatequaternary, tertiary, secondary
and primary carbons in 1b–1g and 2b–2g. Because of the
complexity of the isomeric mixture of 1c and 1f or 2c and 2f,
respectively, or their low proportion (1g and 2g), the 1H NMR
spectra were not assigned.
∗
´
Correspondence to: Armando Ariza-Castolo, Centro de Investigacion y de
´
Estudios Avanzados del IPN, Apartado postal, 14-740, 07000, Mexico D.F.,
Mexico. E-mail: aariza@cinvestav.mx
´ ´ ´
Unidad Academica de Ciencias Químico Biologicas y Farmaceuticas, Universi-
a
´
dad Autonoma de Nayarit, Tepic Nayarit, Mexico
The preferential conformation of the N-substituent (R2) was
determined based on the chemical shift effect of this group
on pseudoequatorial/pseudoaxial protons at C3 and C7 in the
´
Centro de Investigacion y de Estudios Avanzados del IPN, Apartado postal
b
´
14-740 07000, Mexico D.F., Mexico
c
Magn. Reson. Chem. 2009, 47, 1013–1018
Copyright ꢀ 2009 John Wiley & Sons, Ltd.

R. Montalvo-Gonza´lez and A. Ariza-Castolo
Figure 1. Structure and numbering of ε-lactams 1a–1g and 2a–2g.
Table 1. 1H NMR chemical shifts of ε-lactams (ppm)
3
4
5
6
7
Eq
Ax
Eq
Ax
Eq
Ax
Eq
Ax
Eq
Ax
9
10
11
12
13
Me
1a
1b
1d
1e
2a
2b
2d
2e
2.74
–
2.71
2.82
2.73
2.65
2.71
2.86
2.75
2.69
1.85
1.82
1.93
2.05
1.86
1.80
1.95
2.07
1.85
1.59
1.42
1.40
1.86
1.59
1.41
1.38
1.84
2.01
–
1.84
1.72
1.78
1.32
1.85
1.74
1.81
1.36
1.86
1.85
1.89
2.01
1.84
1.92
1.94
2.08
1.86
1.70
1.44
1.41
1.84
1.93
1.45
1.39
3.79
3.60
3.63
3.64
3.79
3.61
3.64
3.68
3.77
3.94
3.87
3.80
3.77
3.99
3.92
3.82
7.19
7.20
7.21
7.21
8.51
8.50
8.51
8.53
7.35
7.35
7.36
7.34
–
7.21
7.21
7.22
7.19
8.46
8.44
8.45
8.41
7.35
7.35
7.36
7.34
7.08
7.30
7.31
7.28
7.19
7.21
7.21
7.21
7.60
7.59
7.60
7.60
–
1.19
1.01
0.89
–
2.67
2.68
2.74
–
–
1.85
2.03
–
–
1.20
1.03
0.91
2.68
2.70
–
–
–
of these effects were explored using the parent compounds 1a
and 2a as references.
complicated coupling patterns (most of the protons possess up to
five different coupling partners). Hence, to interpret the NMR data,
it was necessary to simulate the the 1H NMR spectra[8] (Fig. 2).
Signal assignment was performed considering the chemical shifts,
multiplicity and connectivity. The root mean square (r.m.s.) error
between the experimental and simulated spectra was 0.11 Hz. This
excellent correlation between the experimental and simulated
Discussion
1H NMR
spectra was obtained when long-range coupling constants (4JH,H
)
The azepinones 1a, 1b, 1d, 1e, 2a, 2b, 2d and 2e give
rise to complex 1H NMR spectra with overlapping signals and
were taken into account.
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2009, 47, 1013–1018

Synthesis and structural determination of ε-lactams by 1H and 13C NMR
Table 2. 1H NMR coupling constants of ε-lactams determined by simulation of experimental spectra (Hz)
3
4
5
6
7
9
10
11
12
2
1a J3,3 = 3.4
3J3,4 = 2.9
3J3,4 = 1.5
4J3,5 = 0.8
4J3,5 = 0.4
2J4,4 = 3.0
3J4,5 = 2.5
3J4,5 = 2.0
4J4,6 = 0.5
2J5,5 = 3.0
3J5,6 = 3.1
3J5,6 = 2.0
4J5,7 = 0.8
4J5,7 = 0.4
2J6,6 = 3.2
3J6,7 = 2.8
3J6,7 = 1.9
3J7,7 = 3.5
3J3,me = 6.7
2J4,4 = 14.0
2J5,5 = 12.8
2J6,6 = 14.0
2J7,7 = 15.4 J9o,10m = 8.0 J10m,11p = 7.3
3
3
3
3
1b J3ax,4eq = 1.3 3J4ax,5ax = 14.0 J5eq,6eq = 5.6 3J6ax,7eq = 1.3
4J9o,11p = 1.3
3J3ax,4ax = 15.6 J4ax,5eq = 2.5 3J5eq,6ax = 3.6 3J6ax,7ax = 10.3
3
4J3ax,5eq = 0.8 3J4eq,5eq = 5.6 3J5ax,6ax = 14.0 J6eq,7eq = 5.6
3
3J4eq,5ax = 3.0 3J5ax,6eq = 3.3 3J6eq,7ax = 1.0
4J4eq,5eq = 1.0 4J5eq,7eq = 1.4
4J5eq,7ax = 0.8
2
3
3
1d J3,3 = 14.0
2J4,4 = 14.8
3J5ax,me = 6.5
2J6,6 = 14.0
2J7,7 = 15.7 J9o,10m = 8.0 J10m,11p = 7.5
3J3ax,4eq = 1.4 3J4ax,5ax = 11.0 J5ax,6ax = 11.1 J6ax,7eq = 1.7
4J9o,11p = 1.3
3
3
3J3ax,4ax = 12.3 J4eq,5ax = 3.4 3J5ax,6eq = 4.0 3J6ax,7ax = 10.8
3
3J3eq,4eq = 8.0 4J4eq,6eq = 1.9 4J5ax,7eq = 0.4 3J6eq,7eq = 6.6
3J3eq,4ax = 1.7
4J3eq,5ax = 0.3
4J3ax,5ax = 0.3
4J5ax,7ax = 0.4 3J6ax,7eq = 1.1
2
2
3
3
1e J3,3 = 14.0
2J4,4 = 14.2
3J5ax,6ax = 12.4 J6,6 = 14.0
2J7,7 = 15.2 J9o,10m = 8.0 J10m,11p = 7.3
3J3ax,4eq = 1.9 3J4ax,5ax = 12.3 J5ax,6eq = 2.8 3J6ax,7eq = 1.2
4J9o,11p = 1.7
3
3J3ax,4ax = 12.4 J4eq,5ax = 2.5
3J6ax,7ax = 10.1
3J6eq,7eq = 7.7
3J6ax,7eq = 1.8
3
3J3eq,4eq = 8.4 4J4eq,6eq = 1.9
3J3eq,4ax = 1.7
2
3
2a J3,3 = 3.4
2J4,4 = 3.0
3J4,5 = 2.5
3J4,5 = 2.0
4J4,6 = 0.5
2J5,5 = 3.0
3J5,6 = 3.1
3J5,6 = 2.0
4J5,7 = 0.8
4J5,7 = 0.4
2J6,6 = 3.2
3J6,7 = 2.8
3J6,7 = 1.9
3J7,7 = 3.5 4J9,11 = 0.4
5J9,12 = 0.8
3J11,12 = 4.8 J12,13 = 8.2
3J3,4 = 2.9
3J3,4 = 1.5
4J3,5 = 0.8
4J3,5 = 0.4
4J11,13 = 1.5
4J9,13 = 2.6
3J3,me = 6.7
2J4,4 = 14.0
2J5,5 = 12.8
2J6,6 = 14.0
2J7,7 = 15.4 J9,11 = 0.3
3J11,12 = 4.8 J12,13 = 8.2
4
3
3
3
2b J3ax,4eq = 2.0 3J4ax,5ax = 14.0 J5eq,6eq = 5.6 3J6ax,7eq = 1.3
5J9,12 = 0.7
4J9,13 = 2.6
4J11,13 = 1.5
3J3ax,4ax = 15.1 J4ax,5eq = 2.6 3J5eq,6ax = 3.6 3J6ax,7ax = 11.5
3
4J3ax,5eq = 0.4 3J4eq,5eq = 6.0 3J5ax,6ax = 14.0 J6eq,7eq = 5.7
3
3J4eq,5ax = 3.0 3J5ax,6eq = 3.3 3J6ax,7eq = 1.0
4J4eq,5eq = 1.0 4J5eq,7eq = 1.4
4J5eq,7ax = 0.8
2J3,3 = 14.0
2J4,4 = 14.1
3J5ax,me = 6.5
2J6,6 = 14.1
2J7,7 = 15.6 J9,11 = 0.3
3J11,12 = 4.8 J12,13 = 8.2
4
3
3J3ax,4eq = 1.4 3J4ax,5ax = 11.0 J5ax,6ax = 11.1 J6ax,7eq = 1.8
5J9,12 = 0.8
4J9,13 = 2.6
4J11,13 = 1.5
3
3
3
3
2d J3ax,4ax = 12.3 J4eq,5ax = 3.4 3J5ax,6eq = 4.0 3J6ax,7ax = 10.8
3J3eq,4eq = 8.0 4J4eq,6eq = 1.9 4J5ax,7eq = 0.4 3J6eq,7eq = 6.6
3J3eq,4ax = 1.7
4J3eq,5ax = 0.4
4J3ax,5ax = 0.4
4J5ax,7ax = 0.4 3J6ax,7eq = 1.1
2J3,3 = 13.5
2J4,4 = 14.4
3J5ax,6ax = 11.0 J6,6 = 14.5
2J7,7 = 15.3 J9,11 = 0.4
3J11,12 = 4.8 J12,13 = 8.2
2
4
3
3
3
2e J3ax,4eq = 1.5 3J4ax,5ax = 11.0 J5ax,6eq = 3.8 3J6ax,7eq = 1.5
5J9,12 = 0.7
4J9,13 = 2.6
4J11,13 = 1.5
3J3ax,4ax = 12.3 J4eq,5ax = 3.5
3J3eq,4eq = 7.6
3J6ax,7ax = 9.9
3J6eq,7eq = 6.7
3J6ax,7eq = 0.9
3
3J3eq,4ax = 1.7
The relative proportions of the structural isomers of the
azepinones (1b and 1g or 2c and 2f) were obtained from the
integrals of the methyl proton signals. The chemical shifts of the
C4 to C6 protons in 1a and 2a were similar (Table 1), indicating
that the amide and N-substituent group have little effect on these
protons.
The nonbonding nitrogen orbital is strongly conjugated
(about 84 kJ/mol) to the antibonding carbonyl π-orbital,[9]
indicating that the aromatic ring is preferably perpendicular
to the amide plane. This is evident because the signal of
the pseudoaxial C7 proton exhibits a larger chemical shift
than the signal of the pseudoequatorial proton. The preference
c
Magn. Reson. Chem. 2009, 47, 1013–1018
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
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R. Montalvo-Gonza´lez and A. Ariza-Castolo
Table 3. 13C NMR chemical shifts of ε-lactams (ppm)
2
3
4
5
6
7
8
9
10
11
12
13
Me t-but
1a
1b
1c
1d
1e
175.68
177.27
173.88
174.97
175.12
37.78
38.81
44.77
36.31
36.73
23.64
32.64
29.23
31.31
24.17
29.00
28.54
37.83
35.84
51.22
29.95
29.39
27.42
36.82
29.83
53.12
52.08
52.54
51.68
52.14
144.66
145.02
144.21
144.25
144.13
126.34
126.50
125.91
125.97
125.93
129.18
129.04
128.74
128.82
128.91
126.51
126.32
126.05
126.13
126.19
–
–
–
–
–
–
–
–
–
–
–
3-Me
4-Me
5-Me
5-t-but
18.54
22.66
22.48
27.51
33.01
19.72
20.28
1f
6-Me
175.07
175.70
37.24
37.48
22.39
23.32
37.92
26.59
33.67
35.80
58.73
55.97
144.44
145.02
125.96
128.49
128.76
127.24
126.05
129.14
–
–
–
–
1g
7-Me
2a
2b
2c
2d
176.02
177.59
174.52
175.47
37.73
38.80
44.98
36.35
23.61
32.51
29.57
31.34
29.19
28.59
38.15
35.99
29.92
29.21
27.89
37.03
53.00
51.88
52.69
51.67
141.07
141.31
140.88
140.75
147.41
147.46
147.29
147.19
147.21
146.62
146.65
147.37
149.86
–
–
–
–
147.39
147.08
147.19
147.10
123.74
123.54
123.60
123.52
134.03
136.06
133.80
133.69
–
3-Me
4-Me
5- Me
18.44
22.60
22.57
2e
5-t-but
174.89
36.19
23.72
50.68
29.53
51.44
140.10
146.40
123.01
132.90
–
27.13
32.64
22.25
20.92
2f
6-Me
7-Me
175.67
176.12
37.47
37.32
22.95
23.20
38.08
26.65
34.20
35.95
58.54
56.04
141.11
141.31
–
–
147.19
148.47
123.60
124.09
133.89
136.59
2g
Figure 2. Aliphatic region of the 1H NMR spectrum of the azepinone 1d. Top, simulated spectrum and bottom, experimental spectrum.
of this conformation can be explained by the fact that the
pseudoaxial proton is located in the deshielding region of
the diamagnetic ring current of the aromatic group and the
deshielding cones of the partial double bond produced by the
conjugation between the nonbonding n-orbital and π∗
orbital (Fig. 3).[10]
C O
The two-bond coupling constants fall into the range of
13.5–15.7 Hz; the coupling constants for the protons on C7 are
about 1.5 ( 0.2) Hz larger than those of the protons attached to
C3. This shows that the C3 protons must have a larger geminal
angle[11] (Hax-C3-Heq), which is a result of the conjugation of the
amide group.
The preferred conformation of the seven-membered rings with
an alkyl substituent is a twist chair, as determined by homonuclear
(1H,1H) three-bond coupling constant analyses (Table 2). The
axial–axial three-bond coupling constants range from 10.1 to
12.6 Hz. The higher values correspond to axial protons at C3–C4
and C6–C7, with dihedral angles of 195 5◦ and the lower ones
to axial protons at C4–C5 and C5–C6, with dihedral angles of
155 5◦ or 30 5◦. The latter values are unusual because the
Figure 3. Preferential orientation of the aryl group and the deshielding
current ring effect.
axial protons at C4–C5 or C5–C6 have syn-diaxial interactions.
The proposed conformation is supported by the axial–equatorial
coupling constants ranging from 1.1 to 4.0 Hz. The lower values
correspond to hydrogens bonded to C3–C4 or C6–C7 and the
c
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Magn. Reson. Chem. 2009, 47, 1013–1018

Synthesis and structural determination of ε-lactams by 1H and 13C NMR
Figure 4. 13C chemical shift substituent effect of the methyl group with respect to the heterocycle without the substituent: compounds 1a and 2a.
highest values correspond to hydrogens bonded to C4–C5–C6.
The lower dihedral angle is 65 10◦. This angle is smaller than
expected because, in azepinones derived from oxaziridines with
an alkyl group on C4 of the aliphatic ring, the C4–C5–C6 structure
undergoes a pseudorotation in order to minimize the steric
interaction of the C5 methyl with the C4 and C6 protons.
The equatorial–equatorial coupling constants range from 6.6 to
8.4 Hzindicatingthatthedihedralangleis35 5◦. Thecouplingsof
the equatorial proton were lowest for protons attached to C6–C7
and highest for protons attached to C3–C4. Thus, the dihedral
angle of the equatorial protons attached to C3–C4 is larger than
that of the equatorial protons attached to C6–C7.
big negative γsyn effect.[13] The α substituent effect is largest when
the methyl group is on C5 (6.82 0.02 ppm); the largest effect
for this configuration is because this carbon (C5) has the highest
mobility, with an average dihedral angle between C5–C4–C3–C2
or C5–C6–C7–N1 of nearly 60◦. The largest β substituent effect
is observed on C3, C4 and C5 (about 8.91 0.08 ppm) when the
methyl is attached to C2, C3 or C6. This shows that the average
dihedral angle between these carbons with the ring atoms is larger
than 60◦.
Conclusions
Compounds 1g and 2g with the methyl on C7 have this group
in the pseudoaxial position as determined from the magnitude of
the three-bond coupling constants 3J(CH,CH3) = 7.2 Hz.[12]
A complete conformational and structural description of ε-lactams
has been made by the 1H and 13C NMR analysis. Aryl groups prefer
rotamers in which they are orthogonal to the seven-membered
ring plane. The azepinone rings exchange conformation rapidly
when they are unsubstituted; in substituted rings, they prefer
conformations with an alkyl group at pseudoequatorial position.
However, whenthemethylgroupisatC7, itprefersthepseudoaxial
position.
13C NMR
Complete assignments of the 13C NMR signals of all azepinones
isomers 1a–1g and 2a–2g are listed in Table 3. They were made
consideringtheeffectsofthesubstituents,orientations,connectiv-
ities and the isomeric abundance for 2- or 3-methylcyclohexanone
derivatives (1b and 1g, 1c and 1f or 2b and 2g, 2c and 2f).
The chemical shifts of the signals observed for 1a and 2a are
very similar indicating that the heteroaromatic nitrogen atom
does not have an important inductive effect on the atoms of the
seven-membered ring.
Experimental
The NMR spectra of compounds 1a to 2e were recorded at
18 ◦C with a Bruker 300 Avance spectrometer equipped with a
5-mm multinuclear broadband probe. All spectra were obtained in
CDCl3 solution (0.9 mmol in 0.4 ml of solvent), with chemical shifts
referenced[14] tointernal(CH3)4Si;δ(1H)=0andδ(13C)=0 ppm. 1H
NMR spectra were recorded at 300 MHz (spectral width 6188.1 Hz,
acquisition time 2.648 s, 16 384 data points, recycle delay of 1 s,
equivalent to 30◦ pulse duration, 16 scans). The dihedral angles
were calculated using a generalized Karplus-type equation.[15]
Because of the conjugation between the nonbonding nitrogen
orbital and π∗ orbital, the amide group and the atoms directly
attached must be almost coplanar in the compounds analyzed.
When a substituent is attached to any other atom of the ring
(C3, C4, C5, C6 or C7), only the bonds C3–C4–C5–C6 have the
possibility to undergo a significant pseudorotation. As a result,
the γ effect between the atoms of the ring depends on the
position of the substituent. This is evident from variations in the
magnitude of methyl substituent effects at different positions. The
normal substitution effect of a methyl group is α = 9.1, β = 9.4
and γ = 2.5 ppm when the group is in the anti position,[13]
whereas we observed values of α = 4.1 2.1, β = 6.5 2.8 and
γ = −1.5 0.6 ppm (Fig. 4).
1
The 13C{ H} NMR spectra were recorded at 75.47 MHz (spectral
width 17361.1 Hz, 32 768 data points, recycle delay of 0.01 s,
equivalent to 30◦ pulse duration, 257 scans). Similar conditions
were used to record APT and INEPT spectra.
The H,H-COSY spectra were obtained with the cosy45 pulse
sequence[16] using a 1024 × 512 data point matrix and a
751.20 × 751.20 Hz frequency matrix; the recycle delay was 2 s.
Fourier transformations were carried out using a sine function for
F1 and F2, in absolute value mode.
The 13C,1H-COSY spectra were obtained with the hxco pulse
sequence for the aliphatic region[9] using a 2048 × 256 data point
The lowest α substituent effect arises when the methyl group is
on C3 (1.05 0.02 ppm) or C7 (2.95 0.1 ppm), because these
atoms are bound to the amide group and the dihedral angle
between these atoms (C3–C2–N1–C7) is small. This generates a
c
Magn. Reson. Chem. 2009, 47, 1013–1018
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

R. Montalvo-Gonza´lez and A. Ariza-Castolo
matrix and a 6265 × 751 Hz frequency matrix; pulse time intervals
1 and 2 were set to 2 × 1/4J = 1.85 ms and the recycle delay was
2 s. Fourier transformations were carried out using a square-sine
function for F1 and F2, in absolute value mode.
Mass spectra were determined using a Hewlett-Packard 5890
spectrometer at 70 eV coupled with a gas chromatograph in
electron ionization (EI) mode.
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Syntheses
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The oxaziridine precursors of the lactams were prepared by mixing
1.5molarequivalentsofm-chloroperbenzoicacidand1equivalent
of the corresponding imine[17] in 25 ml of methylene chloride. The
reaction was carried out at 0 ◦C under constant stirring for 1 hour.
Then, 250 ml of water was added to the solution and extracted
three times with 150 ml of CH2Cl2. The portions were combined
and dried over MgSO4. Oxaziridines were purified by using a
flash chromatography alumina (1a–1g) or a silica gel (2a–2g)
column and 90% hexane/10% ethyl acetate as an eluting agent. To
synthesize the lactams, oxaziridines were left at room temperature
and atmosphere during 4 weeks.
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[8] (a) Nuts NMR utility transform software, 2009, http://www.
acornnmr.com. (accessed February 2009); (b) K. Marat,
Spin Works, version 3.0, University of Manitoba, 2009,
http://www.umanitoba.ca/chemistry/nmr/spinworks/index.html.
(accessed May 2009).
Mass spectra data, Karplus-type plots and an example of
assignment are collected in the Supporting information.
Acknowledgements
[9] N. G. Akhmedov, E. M. Myshakin, C. D. Hall, Magn. Reson. Chem.
2004, 42, 39.
[10] C. S. Wannere, P. V. R. Schleyer, Org. Lett. 2003, 5, 605.
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[13] H. O. Kalinowski, S. Berger, S. Braun, Carbon-13 NMR Spectroscopy,
Wiley: Chichester, 1991.
The author would like to thank CONACYT for a research grant (No.
56604).
Supporting information
Supporting information may be found in the online version of this
article.
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc
Magn. Reson. Chem. 2009, 47, 1013–1018