The effect of the nitrogen non-bonding electron pair on the NMR and X-ray in 1,3-diazaheterocycles

Article abstract of DOI:10.1016/j.tetlet.2012.04.077

The effect of the nitrogen nonbonding electron pair on the ¹J_C,H values of 1,3-diazaheterocycles was analyzed and compared to 1,5-diazabiciclo[3.2.1]octanes, which have a restricted conformation. The ¹J_C,H values were measured by observing the ¹³C satellites in the ¹H NMR spectra and then determining the ¹H-coupled ¹³C NMR spectra. The ¹J_C,H values are 10 Hz larger when the α-hydrogen is synperiplanar rather than antiperiplanar to the nonbonding electron pair on the nitrogen, which serves as experimental evidence of the orbital n _N→σ_C,Hap interactions. In addition, the homoanomeric effect from the interactions of the nitrogen lone pair with the antibonding orbital of the equatorial hydrogen, which was in the β position, was discussed (n_N→σ_{C(β),H eq}).

Full text of DOI:10.1016/j.tetlet.2012.04.077

Tetrahedron Letters 53 (2012) 3310–3315
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The effect of the nitrogen non-bonding electron pair on the NMR and X-ray
in 1,3-diazaheterocycles
⇑
Cesar Garcías-Morales, Selene H. Martínez-Salas, Armando Ariza-Castolo
Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN 2508, Col. San Pedro Zacatenco, C.P. 07360, México D.F., Mexico
a r t i c l e i n f o
a b s t r a c t
The effect of the nitrogen nonbonding electron pair on the 1JC,H values of 1,3-diazaheterocycles was ana-
lyzed and compared to 1,5-diazabiciclo[3.2.1]octanes, which have a restricted conformation. The 1JC,H val-
Article history:
Received 17 February 2012
Revised 11 April 2012
Accepted 17 April 2012
Available online 24 April 2012
ues were measured by observing the 13C satellites in the 1H NMR spectra and then determining the 1H-
1
coupled 13C NMR spectra. The JC,H values are 10 Hz larger when the
a
-hydrogen is synperiplanar rather
than antiperiplanar to the nonbonding electron pair on the nitrogen, which serves as experimental evi-
dence of the orbital nN?r⁄C,Hap interactions. In addition, the homoanomeric effect from the interactions
of the nitrogen lone pair with the antibonding orbital of the equatorial hydrogen, which was in the b posi-
tion, was discussed (nN?r⁄C(b),Heq).
Keywords:
Stereoelectronic effect
Nonbonding electron pair
Spin–spin coupling constant
X-ray structure
Ó 2012 Elsevier Ltd. All rights reserved.
Homohyperconjugation
Introduction
elongating the C–Hax bond and thereby decreasing the coupling
constant. It was observed in the case of 1,3-dithianes, that the
1
Stereoelectronic effects have attracted the attention of many
researchers with an interest in organic chemistry1 because of the
major role that conformation plays in cyclic and alicyclic molecules
with X–C–Y and X–C–C–Y composition,2 where X represent an
atom containing a lone pair and Y is an electronegative atom.
1JC,Hax on the
a
-sulfur was 10 Hz greater than the JC,Heq because
of the interaction between rC–S and r⁄C,Heq, which is known as
an inverse Perlin effect.8
There are experimental and theoretical evidence of nonbonding
electron pairs affecting the JC,H coupling constant in 1,3-dioxanes
1
Two of the best known stereoelectronic effect are sigma conjuga-
and 1,3-dithianes. The primary challenge in analyzing the effects of
the nonbonding electron pair on the nitrogen of 1,3-hexahydropyr-
imidine is their rapid inversion on the NMR time-scale and the
conformational changes in the six membered ring.9,10 Anderson
and Davies synthesized 1,5-diazabicyclo[3.2.1]octenes11 with rigid
conformation and provided some NMR evidence of the lone-pair
effect in the 1JC,H coupling constant. Perillo et al.12 synthesized imi-
dazolidines with restricted conformation and this effect has been
theoretically estimated.13
3
tion (rC,X
?
r⁄
)
and the hyperconjugation (nX?r⁄C,Y).4
C,Y
It was determined via 1H NMR that the hydrogens in cyclohex-
ane have different chemical shifts, and their spin–scalar coupling
constants are dependent on their environment, where the spin–
scalar coupling constant of the equatorial hydrogen (Heq) is 4 Hz
higher (1JC,Heq) than the axial one (1JC,Hax).3 This difference in the
1JC,H values has been explained by the hyperconjugation between
the C1–Hax sigma bond and the C2–Hax antibonding orbital
(
rC1,Hax
?
r⁄C2,Hax), which involves the elongation of the C1–Hax
In this Letter, the preparation of imidazolidines, hexahydropyr-
imidines and 1,5-diazabicyclo[3.2.1]octenes with restricted con-
formations is described. The energy barrier of the nitrogen lone
pair in the imidazolidines is over 83 kJ molꢀ1 (1H NMR at
270 MHz and 423 K), which means the nitrogen is comported as
a stereogenic center at room temperature.14 The interactions be-
tween the nonbonding electron pair on the nitrogen with the
1
5
bond and would, therefore, decrease the magnitude of JC,Hax
.
The effect of the nonbonding electron pair on the 1JC,H value has
been analyzed from both theoretical and experimental points of
1
view.6 The one-bond scalar spin coupling constants JC,Hax and
1JC,Heq have different magnitudes for the carbon
a to the oxygen
in 1,3-dioxanes because of the lone pair orientation. Therefore,
the coupling constant for the hydrogen in the equatorial position
was 10 Hz less than for the axial hydrogen.7 This fact has been ex-
plained for the normal Perlin effect by the nO?r⁄C,Hax interactions
r⁄
orbital of the
a
-carbon (nN?r⁄ ,Hax) were revealed using
C,Hax
C
1
a
NMR to determine the magnitude of JC,H and via single-crystal
X-ray diffraction. In addition, the homoanomeric effects from the
interactions between the nonbonding electron pair on the nitrogen
and the r⁄
of the b-carbon (nN?r⁄Cb,Heq) were discussed. This
C,Heq
effect is known as either the Plough or W-effect depending on the
⇑
Corresponding author. Tel.: +52 55 57473727; fax: +52 55 57473389.
E-mail address: aariza@cinvestav.mx (A. Ariza-Castolo).
lone pair orientation.15
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.04.077

C. Garcías-Morales et al. / Tetrahedron Letters 53 (2012) 3310–3315
3311
Table 1
Results and discussion
Select 1H NMR data for compounds 1a through 3d in CDCl3
To analyze the effect the nitrogen nonbonding electron pair has
on the JC,H value, 12 heterocyclic compounds were synthesized
dH
1ª
3.87
1b
4.12
1c
3.91
1d
3.91
1
H2
with restricted conformations (Scheme 1). These compounds were
characterized by 1H and 13C NMR as well as mass spectrometry,
and their connectivities were established via 2D homo- and heter-
onuclear correlation spectroscopy (1H,1H-COSY and 13C,1H-HET-
COR). The conformations were determined via analysis of the
chemical shifts, spin–spin coupling constants, JH,H, and the t-
ROESY spectra. The conformations were also observed via single-
crystal X-ray diffraction in the solid state.
H4sp
H4ap
H6A
H6B
3.20
2.52
3.23
3.81
3.22
2.57
3.39
3.84
3.20
2.55
3.24
3.74
3.30
2.58
3.33
3.76
dH
2a
2b
2c
2d
3
H2
3.62
2.99
2.05
1.85
1.46
2.86
3.62
3.86
3.00
2.0
1.86
1.50
3.03
3.46
3.74
3.00
2.10
1.82
1.51
2.97
3.58
3.73
2.98
2.12
1.77
1.54
3.02
3.58
H4eq
H4ax
H5ax
H5eq
H7A
H7B
Table 1 contains the 1H NMR data for compounds 1a through
2d. A typical 1H NMR spectrum for the aliphatic region of an imi-
dazolidine (1a–1d) consisted of one singlet at 3.95 0.08 ppm, an
AB system for the diastereotopic benzyl hydrogens at 3.28 0.05
and 3.79 0.05 ppm, which had an average 4dH = 0.49 and a
2JH,H = 13 Hz, and an AA0XX0 system with resonances at 3.25
0.05 and 2.55 0.03 ppm to give a 4dH = 0.68 0.3 ppm, these
spectra were assigned using a simulation.16 The 1,3-hexahydropyr-
imidine spectra possessed a single signal between 3.62 and
3.86 ppm that depended on the substituent at C2, an AB system
for both the benzyl group and 4 multiplets for the hydrogens from
C4 to C6. The resonances for both C4 and C6 were
2.995 0.015 ppm for Heq and 2.065 0.055 ppm for Hax and
4ds for the hydrogens on C5 were 0.23–0.39 ppm for the equato-
rial and axial hydrogens, respectively. The 1H NMR spectra for
1,5-diazabiciclo[3.2.1] compounds were observed (Table 1) as an
addition of the imidazolidine and 1,3-hexahydropyrimidine spec-
tra without the benzyl hydrogen signals. The primary difference
dH
3a
3b
3c
3d
H2eq
H2ax
H3ax
H3eq
H6endo
H6exo
H8
3.06
3.32
1.94
1.17
2.87
2.61
5.02
2.99
3.26
1.86
1.10
2.86
2.6
2.97
3.23
1.86
1.11
2.85
2.5
2.95
3.19
1.83
1.08
2.81
2.45
4.83
4.95
4.94
1a
1b
1c
1d
2JH4sp,H4ap
3JH4sp,H5ap
3JH4sp,H5sp
3JH4ap,H5ap
2JH6A,H6B
ꢀ9.5
+5.6
+9.8
+7.8
13.0
ꢀ9.5
+5.3
+9.8
+8.0
13.4
ꢀ9.3
+5.2
+9.4
+7.4
13.1
ꢀ9.5
+5.5
+10.0
+9.0
13.0
2a
2b
2c
2d
2JH4ax,H4eq
2JH5ax,H5eq
3JH4ax,H5ax
3JH4eq,H5ax
3JH4eq,H5eq
2JH7A,H7B
11.5
13
12.1
2.7
3.7
13.1
11.4
12.8
12
2.8
3.9
12
11.5
13.1
11.1
2.8
3.7
13.2
3
12.8
11.8
2.7
3.7
13.3
in these spectra was that their JH2eq,H3ax was less than the line
width (4
m1/2 = 2.4). A W coupling constant was observed for be-
tween H6endo and H8 (4JH,H = 1.3 Hz), while H6exo demonstrated
a W coupling to H2ax (4JH,H = 1.0 Hz); these observations supported
a restricted conformation.
13.6
3a
3b
3c
3d
The difference between the chemical shift for H4sp (d = 3.2) in
compound 1a and H6endo (d = 2.87) in compound 3a was caused
by the orientation of the nitrogen lone-pair. Because the lone-pair
2JHax,H2eq
3JH2ax,H3ax
3JH2ax,H3eq
3JH2eq,H3eq
12.7
13.9
4.7
12.7
14.2
4.8
12.7
14.1
4.8
12.7
13.6
4.8
was synperiplanar to the
a-hydrogens in compound 1a, the
6.3
6.1
6.3
6.2
2JH3ax,
14.3
11.65
8.3
4.9
9.3
14.4
11.8
8.3
5.3
9.3
14.4
11.8
8.3
5.2
9.3
14.3
12.0
8.2
4.9
9.2
hydrogens were electronically deprotected and shifted to higher
frequencies; however, in 3a, the lone-pair was synclinal to the
H3eq
2JH6endo,H6exo
3JH6endo,H7endo
3JH6endo,H7exo
3JH6exo,H7exo
4JH6exo,H2ax
a-hydrogens.
The conformation for the imidazolidines determined by NMR
1.3
1.3
1.3
1.3
(1a–1d) was an envelope with CH2–CH2 eclipsed and the N-Benzyl
group in a pseudoequatorial position trans to the aryl group on C2.
The six membered rings were in the chair conformation with the
nitrogen and C2 substituents in equatorial positions. The bicycle
had a six membered ring with an extended angle for C2 in agree-
The AA0XX0 coupling constants were determined as a second order system by
simulation with the software Spin Works.16a,b The sp and ap positions were assigned
using the nitrogen non-bonding electron pair effect.
Based on the 1H NMR, other isomers were present at a ratio of
less than 200:1, which means the difference in energy between iso-
mers was over 14 kJ/mol. The energy barrier for nitrogen inversion
was greater than 83 kJ/mol (1H NMR at 270 MHz and 423 K) be-
cause it was impossible for us to determine the point of signal coa-
lescence (the AA0XX0 systems in the five membered ring or the AB
system in the benzyl group).
3
ment with a JH2eq,H3ax value near zero, which is indicative of a
90° torsion angle. The conformations of these compounds in solu-
tion were in good agreement with their structures as determined
by solid state X-ray diffraction.
Both the spatial disposition of the hydrogens and the primary
conformation of the compounds were established using the t-
ROESY spectra. Compound 1a–1d demonstrated a nOe between
H2 and the hydrogens antiperiplanar to the nitrogen lone-pair
(H4ap, H5ap) as well as among the benzyl CH2 groups; a correla-
tion between H4sp and H4ap was also observed. Syn-axial interac-
tions were observed for compounds 2a–2d between the H2, H4ax
and H6ax hydrogens in addition to the nOe between H2 and H-
Bn. These observations were consistent with a chair conformation
with an equatorial benzyl group trans to the C2 aryl group. An nOe
was observed between the H8 and both the H2ax and H4ax hydro-
Scheme 1. Structure and labelling of the compounds. Imidazolidines 1, hexahy-
dropyrimidines 2 and 1,5-diazabicyclo[3.2.1]octanes 3. (a) R = phenyl, (b) R = 2-
pyridyl, (c) R = 3-pyridyl, and (d) R = 4-pyridyl.

3312
C. Garcías-Morales et al. / Tetrahedron Letters 53 (2012) 3310–3315
Table 2
Select 13C NMR data of aliphatic region for compounds 1a through 3d in CDCl3
dC
1a
89.12
57.02
50.76
1b
89.31
56.92
50.81
1c
86.62
56.97
50.93
1d
87.67
57.192
51.06
C2
C4
C6
dC
2a
2b
2c
2d
C2
C4
C5
C7
89.14
51.88
24.53
58.55
89.17
51.44
24.65
58.32
85.83
51.49
24.07
58.38
86.74
50.93
23.54
58.41
dC
3a
3b
3c
3d
C2
C3
C6
C8
55.95
18.85
50.13
88.52
56.01
18.63
50.2
55.83
18.65
49.92
86.82
55.79
18.54
49.91
87.33
89.52
1JC,H
1a
1b
1c
1d
C2–H
C4–Hap
C4–Hsp
134.4
132.6
142.3
136.7
133.1
145.8
135.4
133.7
145.33
135.4
133.6
145.7
1JC,H
2a
2b
2c
2d
C2–H
137.3
125.3
136.1
126.5
127.7
139.4
126.5
135.1
125.7
126.8
136.2
126.5
134.3
126.6
128.6
138.1
125.9
132.5
126.6
129.5
Scheme 2. The primary of imidazolidine, hexahydropyrimidines and 1,5-diazabi-
cyclo[3.2.1] octane conformations in solution as determined using the nOe.
C4–Hax
C4–Heq
C5–Hax
C5–Heq
gens in compounds 3a–3d, while H3ax experienced a nOe with the
H6endo and H7endo hydrogens. These observations indicated that
both the nitrogen lone-pairs and the aryl group were in the equa-
torial position of the six membered rings (Scheme 2).
1JC,H
3a
3b
3c
3d
C2–Hax
C2–Heq
C3–Hax
C3–Heq
C6–Hendo
C6–Hexo
C8–H
137.3
140.5
125.3
127.6
138.1
144.5
146.4
132.5
135.5
126.3
127.7
139.3
143.7
146.9
136.7
137.2
125.2
128.1
139.6
143.9
146.8
137.3
137.9
125.3
127.7
140.1
141.5
146.4
A comparison of the chemical shift of H4sp (3.35 0.5 ppm) in
the five membered imidazolidine rings (1a–1d) to that of H6endo
(2.84 0.3 ppm) in the bicycles (3a–3d) can help explain the differ-
ence in the aryl group orientation. This orientation is in the same
direction as the C–H bond in the imidazolidines and orthogonal
to this bond in the bicycles. To determine the chemical shift effect
of the phenyl substituent, we compared compound 1a to both 4
and 5 (Scheme 3). The AA0XX0 coupling pattern in the heterocycle
had a difference for H2 of less than 4d = 0.2 ppm, which was most
pronounced for compounds 4 and 1a (4d 0.69).
the 13C satellite signals in both the 1H NMR and 13C NMR spectra;
these data are presented in Table 2. For compound 1a, it was ob-
served that the JC,H coupling constant with H4ap and H5ap was
132.6 Hz whereas it was 142.3 Hz for the H4sp and H5sp. A differ-
ence of 9.7 Hz was due to the interactions of the nitrogen lone-pair
with the sigma antibonding orbital (r⁄) of the antiperiplanar C–H
bond (nN?r⁄C,Hap). The decrease in the coupling constant of the
synperiplanar hydrogen can be explained by the increased p char-
acter of the C–N bond when the C–H bond was elongated.
1
Effect of the lone pair electrons on the one-bond coupling
1
constant, JC,H, with the
a
and b carbons
1
The coupling constants, JC,H, for the carbons
a and b to the
nitrogen in compounds 1a through 3d were determined using
A one-bond C, H coupling between the H4ax and H6ax carbons
1
with JC,H = 125.3 Hz was observed for compound 2a whereas the
coupling constant for the equatorial hydrogens was 136.1 Hz. The
difference between these coupling constants was caused by the
Scheme 3. 1H NMR data for the imidazolidines substituted at both C2 and the
Scheme 4. Homoanomeric interaction of the six membered rings containing
nitrogen.
nitrogen.

C. Garcías-Morales et al. / Tetrahedron Letters 53 (2012) 3310–3315
3313
interaction between the nitrogen lone-pair and the anti-bonding
sigma C–Hax orbital (nN?r⁄C–H) on the
carbon in compound
2a–2d. The elongation of the C–Hax bond and consequent reduc-
tion in the JC,H4ax and JC,H6ax coupling constants can be similarly
explained for compounds 1a–1d because of the lessened Fermi
contact contribution.17
between the lone pair in the axial position and the r⁄C(b),Heq orbital
(Scheme 4).
a
The primary difference between compounds 1a through 2d and
the compounds 3a–3d was the orientation of the nitrogen
lone-pair, which was in the equatorial position of these com-
pounds because their conformational rigidity did not allow inver-
sion. Compounds 3a–3d did not demonstrate any nN?r⁄
1
1
The hydrogen b to the nitrogen in compound 2a possesses cou-
C(a),H
1
pling constants, JC,H, of 126.5 Hz with H5ax and 127.7 Hz with
interactions because such interactions between orbitals are very
sensitive to the lone pair orientation. The hyperconjugation effect,
nN?r⁄C,H, was observed for H2 in compounds 1a through 2d be-
cause the antibonding orbital, r⁄C,H, was synperiplanar to both of
the nitrogen lone-pairs, which elongated the C–H bond and re-
duced the coupling constant. For instance, compounds 1a and 2a
1
H5eq. For the cyclohexane moiety, the 4 JC,H between Hax and
Heq was approximately 4 Hz, which was explained as hyperconju-
gation of the C1–Hax bond with the antibonding sigma C2–Hax
orbital (rC1,Hax
?
r⁄C2,Hax). The smallest coupling constant differ-
1
1
ence for the JC,H5ax and JC,H5eq hydrogens in 2a–2d relative to
the cyclohexane was because of the homoanomeric effect.18 This
effect causes the nitrogen lone pair to interact with the sigma
antibonding orbital, Cb,Heq (nN?r⁄C(b),Heq). There are two such
interactions; the first is the W-effect, which involves non-bonding
1
have a JC2,H value of 134.4 and 137.3 Hz, respectively. However,
in compounds 3a–3d, the nitrogen lone-pairs are synclinal to
the r⁄
orbital; therefore, there was no hyperconjugation and
C8,H
1
the coupling constant, JC,H
, was unaffected, for example,
electrons in the equatorial position interacting with the r⁄
1JC,H = 146.4 Hz in compound 3a. In addition, the observed differ-
C,Heq
1
1
orbital; the second is caused by the decrease in the coupling
constant with H5ax and H5eq in compounds 2a–2d, which is
known as the Plough effect and explained by the interaction
ences between JC,Hax and JC,Heq in compound 3a was 2.3 Hz for
1
the hydrogens b to the lone pair whereas the 4 JC,H for compound
2a was 1.2 Hz.
Scheme 5. ORTEP drawing of the crystal structure of compounds 1c, 2a, and 3d.

3314
C. Garcías-Morales et al. / Tetrahedron Letters 53 (2012) 3310–3315
Scheme 6. Bonding and non-bonding distance (in pm) as determined by the single-crystal X-ray diffraction structures for compounds 1c, 2a and 3d.
The positions of the hydrogen atoms were determined using a
difference Fourier map. The C–C and C–H bond lengths and angles
Table 3
Select bond distance (pm) and angles for compounds 1c, 2a, and 3d as determined by
X-ray diffractionà
were sensitive to changes in the hybridization of the atoms, which
indicates an orientation change for the nitrogen lone-pair in the
molecules. A comparison of the C2–N1 bond in compound 2a
(147.8 pm), where both lone-pairs are sp to the antibonding
1c
2a
3d
N1–C2
N1–C5
C5–C4
145.4(3) N1–C2
147.3(4) N1–C6
150.3(4)
C5–C4
C5–C6
149.5(4) C21–C2
147.82(16) N1–C8
146.71(18) N1–C2
147.13(14)
148.75(16)
154.4(3)
151.8(2)
151.9(2)
151.6(2)
r⁄
orbital, to the C8-N1 bond in compound 3d (147.13 pm),
C–H
C7–C7#1
C3–C2
C3–C2#1
which has the lone-pair in the equatorial position and, therefore,
sc to the r⁄C–H antibonding orbital, neglects the difference in bond
lengths (Table 3). However, an increase in the C8–N1 bond length
in compound 3d was expected relative to molecule 2a, which had
150.6(2)
149.9(2)
C20–C2
151.97(19) C8–C9
N1–C2–N3 101.2(2) N1–C2–N3 110.74(14) N1#1–C8–N1 106.29(13)
C2–N1–C6 111.45(11) C8–N1–C2 106.65(11)
C4–C5–C6 109.01(15) C2–C3–C2#1 111.51(18)
an nN?r⁄
effect. The explanation for this result is that the
C–H
lone-pair on the nitrogen in 3d was sp to the antibonding
N1–C6–C5 110.55(12) N1–C2–C3
C8–N1–C7
113.24(14)
101.17(10)
r⁄
orbital, and there was a nN?r⁄
type interaction.
C2–N1–C5 106.4(2)
N1–C5–C4 105.1(2)
C2–N3
C–N3
N1–C7–C7#1 105.88(7)
Therefore, the change in the C8–N1 bond length in 3d was ne-
glected and the coupling constant magnitude increased because
of the enhanced p character of C8.
Table 3 shows the bond length and angle data for compounds
1c, 2a, and 3d. It was determined that the C2–H bond lengths for
compounds 1c and 2a were 106 and 101.3 pm, respectively, but
for compound 3d, the C8-H length was only 98.8 pm, which was
X-ray diffraction
We obtained adequate crystals of compounds 1c, 2a, 2d, 3a and
3d for structural analysis by X-ray diffraction (Scheme 5), which
indicated compounds 1c and 2a had each nitrogen lone-pair oriented
on the same side in the axial position, while in the structure of com-
pounds 3a and 3d, the lone-pairs were equatorial. The aromatic ring
at C2 in the single crystals of monoheterocycles 1c and 2a was ob-
served in equatorial position in the symmetry plane that bisected
the five or six membered ring, whereas the aryl group in compounds
3a and 3d were perpendicular to the C2–H bond (Scheme 5). This
implies that the solubility of compound 3 in organic solvents was
better than the other materials.
a significant reduction due to the nN?r⁄
effect.
C–H
Compounds 2a–2d display Plough interactions, which explains
1
their different JC,H values, and the homoanomeric W-effect was
observed in compounds 3a–3d. Scheme 6 shows the C–N, C–C
and C–H distances obtained by crystallography. It was observed
that C–Hax was longer than C–Heq for the six membered rings
(compounds 2a and 3d), while the distance between the nitrogen
with a b-carbon was longer in compound 3d than for 2a. These
data show that the Plough interaction competes with the
homoanomeric W-effect in 1,3-diazacyclehexanes.
Conclusion
à
Crystal data: 1c: Monoclinic, P21/n, a = 604.10(2) b = 1592.20(6) c =
1936.60(2)pm, b = 90.646°(4), Z = 4,
dent reflections (Rint = 0.0271), R1 = 0.0474 for 4161 with I > 2
all data, 318 parameters, GOF = 1.042. 2a, monoclinic, P21/n, a = 608.70(6)
b = 1688.20(3) c = 1961.00(5)pm, b = 98.330°(3), Z = 4, Calcd = 1.141, h = 4.18–
26.00°, 3732 independent reflections (Rint = 0.0360), R1 = 0.0474 for 3732 with
I > 2 (I), wR2 = 0.0982 for all data, 339 parameters. GOF = 1.042. 3d, orthorhombic,
Pbnm, a = 696.60(3) b = 1360(4) c = 1102.40(7)pm, Z=8, Calcd = 1.203, h = 2.99–
27.44°, 1231 independent reflections (Rint = 0.0427), R1 = 0.0430 for 1231 with
I > 2 (I), wR2 = 0.1057 for all data, 103 parameters, GOF = 1.037.
q
Calcd = 1.175, h = 3.31–27.50°, 4161 indepen-
The evidence obtained by NMR and single-crystal X-ray
diffraction indicated that the nitrogen lone pair electrons in
r
(I), wR2 = 0.1143 for
q
r
There are additional factors that complicate the comparison as the double
hyperconjugation (Alabugin, I. V.; Manoharan, M. J. Org. Chem. 2004, 69, 9011–9024)
and the rehybridization (Alabugin, I.V.; Manoharan, M. J. Compt. Chem. 2007, 28, 373–
390), both were shown to change the properties of C–H bonds in related systems.
q
r

C. Garcías-Morales et al. / Tetrahedron Letters 53 (2012) 3310–3315
3315
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Acknowledgments
Funding for this research was provided by CONACyT (Research
Grant No. 56604). C.G.-M. express his gratitude to CONACyT for
providing their scholarships.
Supplementary data
Supplementary data (the crystallographic data for compounds
1c, 2a, 2d, 3a and 3d have been deposited in the Cambridge Crys-
tallographic Data Centre, with the deposition numbers CCDC
848653, 849019, 867286, 848463 and 848654, respectively. These
data can be obtained free of charge from www.ccdc.cam.ac.uk/data
request/cif) associated with this article can be found, in the online
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