F
Synlett
L. Chavelas-Hernández et al.
Letter
1
forming the C (4) chain pattern is typical of many
tramethylated -lactams, the ASIS effect is lower than that
in the other lactams synthesized. In -lactams with aniso-
tropic substituents, it was observed that protons H-3 and
H-4 are already affected by the anisotropy of the substitu-
ent itself. Consequently, an intercalative interaction be-
tween the -lactam and benzene-d6 might overestimate
these changes. From a theoretical point of view, we have
demonstrated that at least one staking interaction between
the -lactam and the molecule of benzene is necessary to
produce the changes in the chemical shifts. 15N HSQC re-
sults confirm the presence of a deshielded effect over the
amide moiety while the protons of the ring are shielded.
1
N−H···O=C hydrogen-bonded systems (N−H, 0.86 Å; H···O,
.00 Å; N···O, 2.857 Å; ∠N−H···O, 175°) (Figure 13b).
2
Intermolecular interactions of 3,3,4,4-tetramethylazeti-
din-2-one (7) were analyzed by using a Hirshfeld surface,20
a powerful technique for understanding the nature of the
intermolecular interactions within a crystalline structure.
The surface was drawn from single-crystal X-ray structures
in the CIF format by using Crystal Explorer software.21 The
surface was mapped over the dnorm function in the range
0
.6−2.6 Å; the red regions show contact points shorter than
the sum of the van der Waals radii with negative dnorm
complementary hollows). The blue regions are contact
(
sites longer than the sum of the van der Waals radii with
dnorm negative equal to zero (bumps where the surfaces of
two molecules touch each other). For compound 7, red ar-
eas on the surface mapped with dnorm function were located
on the amide moieties due to the formation of hydrogen
bonds (Figure 14a).
Funding Information
Consejo Nacional de Ciencia y Tecnología (CB2015/256653).
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Acknowledgment
We would like to thank CONACyT for financial support (Project No.
CB2015/256653). L.C.-H., J.R.V.-C., and M.G.V.-R. are grateful to CONA-
CyT for scholarships.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691498.
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References and Notes
(
(
1) Williams, D. H.; Wilson, D. A. J. Chem. Soc. B 1966, 144.
2) Rummens, F. H. A.; Krystynak, R. J. Am. Chem. Soc. 1972, 94,
914.
6
Figure 14 (a) Hirshfeld surface for 3,3,4,4-tetramethylazetidin-2-one
(3) Hatton, J. V.; Richards, R. E. Mol. Phys. 1962, 5, 139.
(4) Bothner-By, A. A.; Glick, R. E. J. Chem. Phys. 1957, 26, 1651.
(7) mapped with dnorm. (b) Representative 2D fingerprints plots.
(
(
(
(
5) Laszlo, P.; Schleyer, P. von. R. J. Am. Chem. Soc. 1964, 86, 1171.
6) Schneider, W. G. J. Phys. Chem. 1962, 66, 2653.
7) Schaefer, T.; Schneider, W. G. J. Chem. Phys. 1960, 32, 1218.
8) Klinck, R. E.; Stonthers, J. B. Can. J. Chem. 1962, 40, 1071.
Decomposition of this surface to provide a molecular
fingerprint (a directly accessible 2D plot that provides the
full distribution of interactions) was performed by using di
(9) Barfield, M.; Grant, D. M.; Ikenberry, D. J. Am. Chem. Soc. 1975,
97, 6956.
10) Hatton, J. V.; Schneider, W. G. Can. J. Chem. 1962, 40, 1285.
11) Laszio, P.; Engler, E. M. J. Am. Chem. Soc. 1971, 93, 1317.
12) Kalyanam, N. J. Chem. Educ. 1983, 60, 635.
and d , which are defined as the distances from the surface
e
(
(
(
(
of the Hirshfeld surface to the nearest core within or out-
side the surface, respectively. In the 2D fingerprint plots of
7
, H−H interactions predominate, with a percentage of 74%;
13) Yukihiko, I.; Taku, M. Bull. Chem. Soc. Jpn. 1967, 40, 2030.
these appear where d ≈ d near the van der Waals radius of
e
i
(14) Williams, D. H.; Bhacca, N. S. Tetrahedron 1965, 2021.
(15) Hernández-Vázquez, L. G.; Leyva, M. A.; Metta-Magaña, A. J.;
Escalante, J. Helv. Chim. Acta 2012, 95, 2218.
the hydrogen atom (1.20 Å). The percentage of O−H/O−H
contacts is 22.7%, and these appear as a pair of long sharp
spikes characteristic of a strong hydrogen bond (Figure
(
16) N-Alkylation of -Lactams; General Procedure
A 10 mL flask equipped with a magnetic stirrer was charged
with the appropriate -lactam (1 mmol) in anhyd THF (5 mL).
14b). The minimum contributions are attributed to
N−H/H−N and C−H/H−C contacts.
The solution was cooled to –10 °C and treated with Bu NBr (0.1
4
In conclusion, we have demonstrated an ASIS effect in
eight -lactam derivatives by using deuterated chloroform
and benzene solvents. The stacking adduct of the benzene
ring with the lactam ring plays a determining role in chem-
ical-shift changes. N-Methyl groups exhibited the best
shielded effect in H-4 lactam protons, whereas in te-
equiv), the appropriate alkyl iodide or bromide (3 equiv), and
freshly ground KOH pellets (1.6 equiv). After 2 h, the tempera-
ture was allowed to rise to –7 °C and the mixture was stirred
overnight. The temperature was then increased to 0 °C and,
when the reaction was nearly complete (TLC; 5 h), it was
quenched with sat. aq NH Cl. The mixture was extracted with
4
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2019. Thieme. All rights reserved. Synlett 2019, 30, A–G