Synthesis, 1D and 2D NMR spectral assignments, and stereochemical studies of some 4,8,9,10-tetraaryl-1,3-diazaadamantan-6-one oximes

Article abstract of DOI:10.1007/s11224-019-01326-9

A series of 4,8,9,10-tetraaryl-1,3-diazaadamantan-6-one oximes (4a-4e) have been synthesized. ¹H and ¹³C NMR spectra of these oximes were recorded. Chemical shifts have been assigned and the stereochemistry of the compounds was established using 1D and 2D NMR spectral data. A detailed spectral investigation was carried out for one of the representative compounds (4a) with COSY, NOESY, HMQC, HMBC, DEPT-135, and N NMR spectral data. The NMR result clearly indicated the twin chair conformation of the two piperidine rings. The NMR results proved the axial orientation of two aryl groups (C4 and C10) in one piperidine ring and equatorial orientation of two aryl groups (C8 and C9) in another piperidine ring. The effect of allylic (A^1,3) interaction between the oxime hydroxyl group and H-5e has been observed. Long-range coupling between H-10e and H-2 which are in ‘W’ arrangement is noted.

Full text of DOI:10.1007/s11224-019-01326-9

Structural Chemistry
https://doi.org/10.1007/s11224-019-01326-9
ORIGINAL RESEARCH
Synthesis, 1D and 2D NMR spectral assignments, and stereochemical
studies of some 4,8,9,10-tetraaryl-1,3-diazaadamantan-6-one oximes
G. Vengatesh1 & M. Sundaravadivelu1
Received: 15 February 2019 /Accepted: 20 March 2019
#
Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract
1
A series of 4,8,9,10-tetraaryl-1,3-diazaadamantan-6-one oximes (4a-4e) have been synthesized. H and 13C NMR spectra of
these oximes were recorded. Chemical shifts have been assigned and the stereochemistry of the compounds was established using
1D and 2D NMR spectral data. A detailed spectral investigation was carried out for one of the representative compounds (4a)
with COSY, NOESY, HMQC, HMBC, DEPT-135, and N NMR spectral data. The NMR result clearly indicated the twin chair
conformation of the two piperidine rings. The NMR results proved the axial orientation of two aryl groups (C4 and C10) in one
piperidine ring and equatorial orientation of two aryl groups (C8 and C9) in another piperidine ring. The effect of allylic (A1,3
)
interaction between the oxime hydroxyl group and H-5e has been observed. Long-range coupling between H-10e and H-2 which
are in ‘W’ arrangement is noted.
15
.
.
.
.
.
Keywords 2D NMR N NMR Oxime Tricyclic compound Conformation Warrangement
Introduction
24]. The biological activity of the organic compounds depends
primarily on the stereochemistry of the molecules and hence, it
is essential to establish the configuration and conformation of
the synthesized molecules [25, 26]. The oxime of diazabicyclic
ketones have shown antimicrobial and antifungal activities and
the stereochemistry of these compounds have been studied
using 1D and 2D NMR spectroscopic techniques [27]. In con-
tinuation with our earlier work on 1,3-diazaadamantanan-6-
ones [7], we report here the synthesis and stereochemical study
of oximes of 4,8,9,10-tetraaryl substituted 1,3-diazaadamantan-
6-ones using 2D-NMR spectroscopic techniques such as 1H-1H
COSY, NOESY, TOCSY, HMQC, and HMBC.
The chemistry of bicyclic and tricyclic compounds containing
piperidine nucleus is of great interest due to their stereochem-
ical behavior and biological activities [1–5]. Synthesis, stereo-
chemistry, and biological activities of azabicyclononanone
and diazaadamantane derivatives have been widely reported
[6–13]. Introduction of oxime functional group in the cyclic
compounds have been used for some important pharmaceuti-
cal and synthetic chemistry applications, and often act as
chemical building blocks for the synthesis of agrochemicals
and pharmaceuticals [14, 15]. The Oximes show important
biological activities such as antidepressants, analgesic, anti-
inflammatory, fungicidal, antitumor, herbicides, and antimi-
crobial activity [16–22]. Besides, oximes being electron donor
groups, they can be used as ligands which are effective in the
DNA binding and cleavage activity of heterocyclic bases [23,
Experimental
General procedure for the synthesis of compound
1a-1e and 2a-2e
Compounds 2,4,6,8-tetraaryl-3,7- diazabicyclo [3.3.1] nonan-
9-ones (1a-1e) were synthesized as one-pot synthesis by dou-
ble Mannich condensation of acetone, substituted benzalde-
hyde and ammonium acetate in 1:4:2 ratio in ethanol [9]. The
bicyclic compounds (1a-1e) were converted into 4,8,9,10-
tetraaryl-1,3-diazaadamantan-6-ones by literature methods
[7, 28] Scheme 1. Numbering and structure of the newly syn-
thesized compounds shown in Scheme 2.
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s11224-019-01326-9) contains supplementary
material, which is available to authorized users.
* M. Sundaravadivelu
msundargri@gmail.com
1
Department of Chemistry, The Gandhigram Rural Institute-Deemed
to be University, Gandhigram, Tamil Nadu 624302, India

Struct Chem
Scheme 1 Synthesis of 2,4,6,8-Tetraaryl-3,7- diazabicyclo [3.3.1] nonan-9-one (1a-1e), 4,8,9,10-Tetraaryl-1,3-diazatricyclo [3.3.1.1] decan-6-one (2a-
2e), 4,8,9,10-Tetraaryl-1,3-diazabicyclo [3.3.1] nonan-9-one oxime (3a-3e), and 4,8,9,10-Tetraaryl-1,3-diaazaadamantane-6-one oxime (4a-4e)
General procedure for the synthesis of Oximes (4a-4e)
Oximes (4a-4e) were synthesized by two methods:
already reported [9]. These oximes (3a-3e) were refluxed
with paraformaldehyde in chloroform solvent for 3 h.
After completion of the reaction, the solvent was removed
and the resulting diazaadamantanone oximes were recrys-
tallized using chloroform solvent.
a) Oximes of 2,4,6,8-tetraaryl-3,7- diazabicyclo [3.3.1]
nonan-9-ones (3a-3e) were prepared by using the method
Scheme 2 a) Numbering for 1D
and 2D NMR spectral analysis of
Compound 4a-4e. b) Structure of
the newly synthesized
a
compounds (4a-e)
b

Struct Chem
b) An attempt was made to synthesis the oximes (4a-4e)
from 1,3-diazaadamantanones (2a-2e). Interestingly, the
reaction yielded a mixture of oximes of diazabiclononanones
(3a-3e) (predominantly) and oximes of diazaadamantanones
(4a-4e).
AQ 0.28 s, SF 400.23, LB 0 Hz, D1 1.90 s. NOESY: TD 2048
(F2), TD 256 (F1) NS 4, DS 32, SWH 4132.2 Hz, AQ 0.24 s,
SF 400.23, LB 0 Hz, D1 2.00 s. TOCSY: TD 2048 (F2), TD
256 (F1) NS 8, DS 16, SWH 4310.3 Hz, AQ 0.23 s, SF
400.23, LB 0 Hz, D1 2.01 s. HMQC: TD 1024 (F2), TD
128 (F1) NS 4, DS 16, SWH 3937 Hz, AQ 0.13 s, SF
400.23 (F2), SF 100.63 (F1), LB 0 Hz, D1 1.46 s. HMBC:
the parameters were very similar to those used in the HMQC
experiment, TD 2048 (F2), TD 128 (F1) NS 4, DS 16, SWH
3937 Hz, AQ 0.26 s, SF 400.23 (F2), SF 100.63 (F1), LB
0 Hz, D1 1.43 s.
Spectral measurements
General
Melting points were determined by the open capillary method.
FT-IR spectra were recorded on a JASCO FT/IR-4700 instru-
ment. All the NMR spectra were recorded on a Bruker
AVANCE III HD 400 MHz spectrometer.
Result and discussion
FT-IR
NMR spectra
The FT-IR spectral values of the compounds 4a-4e are
shown in Table 1 and 4a is considered as the representa-
tive compound. Formation of the product initially con-
firmed by FT-IR spectroscopy, which shows the disap-
pearance of the carbonyl group stretching frequency and
appearance of –OH and C=N stretching frequencies. The
weak band at 3431 cm-1 corresponding to the oxime hy-
droxy group. The aromatic C–H and C=C frequency band
appeared at 3031–3062 and 1492 cm-1 respectively. The
aliphatic C–H deformation bands appeared at 2847–
2955 cm-1, refer to the methylene bridge and piperidine
CH groups. The oxime C=N band is present at 1655 cm.
Recording of one-dimensional NMR spectra
NMR spectra of all the synthesized compounds were recorded
at 295–298 K. The 1D 1H and 13C NMR spectra were mea-
sured using 3 mg and 20 mg of compound dissolved in 0.5 ml
of CDCl3 solution respectively; TMS was used as internal
standard, in 15N NMR spectrum reference using formamide.
The pulse conditions were as follows: H NMR spectra: num-
ber of data points (TD) 65,536, number of scans (NS) 16,
dummy scans (DS) 2, spectra with (SWH) 8012.8 Hz, acqui-
sition time (AQ) 4 s, spectrometer operating frequency
400.23, line broadening (LB) 0.30 Hz, Recycle Delay (D1)
1.0 s. 15N NMR spectra: TD 3276, NS 885, DS 4, SWH
20380.4 Hz, AQ 0.80 s, SF 40.554, LB 0.25 Hz, D1 10.0 s.
15C NMR spectra: TD 65536, NS 1024, DS 4, SWH
24038.4 Hz, AQ 1.3 s, SF 100.63, LB 1.00 Hz, D1 2.0 s.
DEPT 135: TD 65536, NS 256, DS 8, SWH 16129 Hz, AQ
2.0 s, SF 100.63, LB 1.00 Hz, D1 2.0 s.
Proton NMR chemical shift analysis
of 4,8,9,10-tetraphenyl-1,3-diazaadamantan-6-one
oxime (4a)
In the proton NMR spectrum of 4a, each of the benzylic
protons (H-4,8,9 and 10) and bridged-head protons (H-5 and
7) gives rise to a distinct singlet. The bridge-head protons H-
5 and H-7 appear as a broad singlet at δ 4.73 ppm with the
half-with, W1/2 of 6.28 Hz and at δ 3.85 ppm with the W1/2
of 5.59 Hz respectively. The H-5 proton shows up in the
downfield region due to A1,3 allylic interaction (Fig. 1) of
the oxime group [29]. The chemical shift differences be-
tween the two bridge-head protons Δ5,7 is δ 0.88 ppm,
Recording of two-dimensional NMR spectra
All the 2D NMR spectra were recorded on the same instru-
ment using 5 mg and 20 mg of compound dissolved in CDCl3
solution. The pulse conditions were as follows: 1H-1H COSY:
TD 2048 (F2), TD 128 (F1) NS 1, DS 16, SWH 3571.4 Hz,
Table 1 IR spectral data (cm–1)
of 4a–4e
Entry
OH
C=N
Aromatic C–H stretching
Aliphatic C–H stretching
Aromatic C=C
4a
4b
4c
4e
4d
3431
3413
3429
3420
3430
1655
1643
1631
1611
1604
3059, 3031, 3062
3174, 3050, 3027
3183, 3054
2955, 2917, 2847
2945,2921, 2868
2947, 2878
1492
1512
1493
1510
1507
3069
2996, 2947, 2833
2947, 2884
3198, 3076

Struct Chem
Fig. 1 Oxime hydroxy group and
H-5 A1,3 allylic interaction of
compound 4a
obviously by the allylic interaction present in the –C=N–O
and H-5 proton. Due to this interaction, the H-5 and C-5
have acquired positive and negative charges respectively.
Benzylic protons H-4 and H-9, adjacent to C5-H appear as
a singlet at δ 4.66 (W1/2 of 4.83 Hz) and at δ 4.70 ppm (W1/2
of 5.92 Hz) respectively. Other two benzylic protons H-8
and H-10 resonate at δ 4.75 (W1/2 of 7.03 Hz) and at δ
4.60 ppm (W1/2 of 4.77 Hz) respectively. The signal at δ
7.75 ppm is due to oxime OH and it is confirmed by D2O
exchange analysis. H NMR chemical shift values of five
1
new oximes are given in Table 2. All the proton positions
and chemical shift values are assigned and confirmed by
1H-1H COSY, NOESY, and TOCSY techniques. For better
1
understanding, the H-1H COSY, TOCSY, and NOESY cor-
relations are presented in Table 3. COSY and NOESY spec-
tra are reproduced in Figs. 2 and 3 respectively.
Table 2 H NMR data of (δ, ppm) of 4a-4e
Entry
H-2
H-4
H-5
H-7
H-8
H-9
H-10
N–OHa
Others
4a
4.37
4.29
4.26
4.31
4.27
4.66
4.60b
4.51
4.62c
4.55
4.73
4.65
4.66
4.56
4.67
3.85
3.73
3.71
3.78
3.72
4.75
4.60b
4.61
4.67
4.62
4.70
4.60b
4.58
4.66
4.61
4.60
4.54
4.45
4.62c
4.49
7.75
7.75
7.58
7.88
7.43
–
4b
3.62, 3.81
4c
–
4d
2.09, 2.35
4e
–
Entry
Aryl group protons attached at C4 and C10
Aryl group protons attached at C8 and C9
Ortho
Meta
Para
6.76
–
Ortho
Meta
Para
7.30
–
4a
4b
4c
4d
4e
7.14–7.16
6.91–6.94 (m)
6.99 (d)
6.80–6.83 (m)
6.36 (d)
6.82 (d)
6.60 (d)
6.54 (t)
7.64–7.70 (m)
7.52–7.58 (m)
7.50–7.56 (m)
7.50–7.55 (m)
7.55–7.62 (m)
7.38–7.43 (m)
7.01–7.03
7.37–7.40 (m)
7.19 (t)
–
–
6.97 (d)
–
–
7.05–7.08 (m)
–
7.10–7.13 (m)
–
a OH proton of the oxime is confirmed by identified by D2O exchange
b Merged with H-9 and H-10
c Merged with H-8 and H-9

Struct Chem
Table 3 Correlation in the 1H-1H COSY and NOESY chemical shift value of compound 4a
Signal (in ppm)
Correlation in COSY
Correlation in NOESY
Correlation in TOCSY
4.37 (H-2)
4.66 (H-4)
4.73 (H-5)
3.85 (H-7)
4.75 (H-8)
4.70 (H-9)
4.60 (H-10)
–
4.60, 4.66, 7.64–7.70
4.37, 7.14–7.16, 7.64–7.70
–
4.60, 4.66, 4.70, 4.75
3.85, 4.60, 7.14–7.16
4.70, 4.75 (w)
4.60, 4.66, 4.75 (s)
3.85, 7.64–7.70
4.70, 7.64–7.70
3.85 (w), 7.14–7.16
4.60, 4.70, 4.73, 6.80–6.83, 7.14–7.16
3.85, 4.66, 4.70
4.60, 4.75, 7.14–7.16, 7.64–7.70
3.85, 7.14–7.16, 7.64–7.70
7.14–7.16, 7.64–7.70
3.85, 7.14–7.16, 7.64–7.70
4.37, 4.60, 4.66, 4.75
3.85, 4.37, 7.30, 7.38–7.43, 7.64–7.70
4.73, 7.30, 7.38–7.43, 7.64–7.70
3.85, 4.66, 4.75, 6.80–6.83, 7.14–7.16
w, weak correlation; s, strong correlation
In COSY, one of the bridge-head protons, H-7, is correlated
with the two equatorial protons, H-4 and H-10, and one axial
proton, H-8. Another bridge-head proton H-5 has COSY cor-
relation with adjacent axial proton H-8 and H-9. There is a
correlation of H-8 and H-9 with ortho protons of the C-8 and
C-9 phenyl groups at δ 7.64–7.70 ppm. A similar observation
is noted for another two benzylic protons at H-4, 10 and ortho
protons of the C-4, 10 phenyl groups at δ 7.14–7.16 ppm. The
long-range correlation is further assigned using TOCSY
spectrum.
of C-8, 9 phenyl groups. NOESY studies unequivocally
proved the equatorial orientation of H-4,10 protons and axial
orientation of H-8, 9 protons.
15N NMR exhibit two signals, one at δ 199.98 ppm due to
piperidine nitrogen and another at δ 406.94 ppm due to oxime
nitrogen.
Carbon NMR chemical shift analysis
of 4,8,9,10-tetraphenyl-1,3-diazaadamantan-6-one
oxime (4a)
In the NOESY spectrum, H-5 and 7 protons have a corre-
lation with all the ortho protons of the phenyl groups at C-4,
10, 8, and 9. H-7 proton has NOESY correlation with H-8, 10
protons. H-2 has a correlation with H-4, 10 and ortho protons
The 13C NMR analysis for all the synthesized compounds
have been carried out with the aid of DEPT-135, 1H-13C one
1
bond correlations (HMQC) and H-13C multiple bond
Fig. 2 COSY spectrum of 4,8,9,10-tetraphenyl-1,3-diaazaadamantane-6-one oxime (4a)

Struct Chem
Fig. 3 NOESY Spectrum of 4,8,9,10-tetraphenyl-1,3-diaazaadamantane-6-one oxime (4a)
Fig. 4 DEPT-135 spectrum of 4,8,9,10-tetraphenyl-1,3-diaazaadamantane-6-one oxime (4a)

Struct Chem
Fig. 5 HMQC spectrum of 4,8,9,10-tetraphenyl-1,3-diaazaadamantane-6-one oxime (4a)
correlations (HMBC) of representative compound 4a and they
are presented in Figs. 4, 5, and 6. Complete carbon chemical
shift assignments of compounds 4a–4e are presented in
Table 4. A careful analysis of Table 4 provides information
about the effect of oxime group in the chemical shift of
heterotricyclic ring carbons. In the DEPT-135 spectrum of
Fig. 6 HMBC spectrum of 4,8,9,10-tetraphenyl-1,3-diaazaadamantane-6-one oxime (4a)

Struct Chem
Table 4 13C NMR data of (δ, ppm) of 4a-4e
Entry C-2
C-4
C-5
C-6
C-7
C-8
C-9
C-10
60.50
Others
4a
4b
4c
68.50
61.78
61.07
60.98
61.55
65.55
31.23
31.54
30.68
31.52
35.55
162.63
162.85
159.24
162.89
163.88
37.33
37.64
36.97
37.59
41.86
70.26
69.78
69.34
70.10
74.05
68.11
67.62
67.17
67.96
71.87
–
67.82
68.06
68.20
72.64
59.86 55.14
59.74
60.24 20.79
–
4d
4ea
64.28
–
Entry Aryl group chemical shift attached at C4 and C10
Ipso Ortho Meta
Aryl group chemical shift attached at C8 and C9
Ipso Ortho Meta
para
para
4a
4b
4c
139.89, 140.31 127.85, 128.25 125.95, 126.27 138.89, 138.98 126.81–127.07 128.88, 128.91 127.22
132.64, 133.00 128.92, 129.33 112.69, 112.85 130.97, 131.07 127.93, 128.11 114.16, 114.19 158.59
132.02, 132.31 129.31, 129.76 127.07, 127.26 132.02, 132.31 128.11, 128.31 129.02, 129.08 133.02
138.89, 138.98
130.97, 131.07
132.02, 132.31
135.10, 135.45
4d
4ea
136.01, 136.11 127.82
126.75, 126.93 135.10, 135.45 127.67–128.18 129.50, 129.54 136.67
140.51, 141.02 134.29–134.78 118.22–118.60 139.26, 139.35 133.08–133.34 120.27–120.53 165.26–167.03 139.26, 139.35
a
13 C NMR spectrum of 4e is run by mixture of solvent (CDCl3 and DMSO)
4a, the aliphatic region signals at δ 31.23, 37.33 ppm
(assigned due to C-5 and C-7) and δ 70.26, 68.16, 61.83,
and 60.56 ppm (assigned due to C-8, C-9, C-4 and C-10 ben-
zylic carbons) exhibit in the upward direction. The signal at δ
68.50 ppm exhibit in the downward direction is assigned due
to C-2 carbon (–N–CH2–N–). The signal at δ 125.95–
128.91 ppm are assigned due to aromatic carbons and signal
at δ 162.63 ppm is assigned due to C-6 carbon. Four ipso
carbons of the aryl groups and C-6 carbon, which are quater-
nary carbon could not be seen in the DEPT-135 spectrum.
In HMQC, 13C NMR signal at δ 68.50 ppm (C-2) is corre-
lated to H-2 at δ 4.37 ppm confirming N–CH2–N protons. In
HMQC spectrum, the proton signals at δ 3.85 (H-7) and 4.73
(H-5) ppm correlation with the carbon signal at 37.33 ppm and
31.23 ppm, which lead to the assignment of this signals to the
C-7 and C-5 carbon respectively. Similarly, four benzylic pro-
tons at 4.75 (H-8), 4.70 (H-9), 4.66 (H-4), and 4.60 (H-10) are
correlated with the corresponding carbon signal at 70.26
(C-8), 68.16 (C-9), 61.83 (C-4), and 60.56 (C-10)
respectively.
HMBC spectrum of 4a showed the correlation of the ali-
phatic proton signal at δ 3.85 (H-7), 4.75 (H-8), 4.70 (H-9),
4.66 (H-4), 4.73 (H-5), and 4.60 (H-10) ppm with carbon
signal at 162. 63 (C-6), which led to the assignment of this
signal to the oxime carbon (C-6). Since the proton signal at δ
4.37 ppm (H-2) does not correlation with carbon signal at δ
162.63 ppm, this could be assigned to N–CH2–N group. Other
HMQC and HMBC correlations are shown in Table 5.
Conformation and BW^ arrangement
In order to understand the conformational analysis of cyclic
ring, vicinal coupling constants are a more important param-
eter. However, in the present oximes, coupling constants
values could not be resolved because all the protons exhibit
separate singlet. Therefore, conformation of the two piperidine
Table 5 Correlation in the HMQC and HMBC spectra data of compound 4a
Signal (δ in ppm)
HMQC correlations
HMBC correlations
4.37 (H-2)
68.50
61.78, 68.11, 70.26
4.66 (H-4)
61.78
31.23, 60.50, 68.11, 127.85, 139.89, 162.63
162.63
4.73 (H-5)
31.23
3.85 (H-7)
37.33
70.26, 162.63
4.75 (H-8)
70.26
31.23, 60.50, 68.11, 126.98, 138.98, 138.89, 162.63
37.33, 61.78, 68.50, 127.07, 127.19, 138.89, 138.98, 162.63
31.23, 61.78, 70.26, 127.85, 139.89, 162.63
127.07, 126.98, 128.25, 139.89, 140.31
60.50, 125.95, 126.81, 127.85, 128.25
126.81
4.70 (H-9)
68.11
4.60 (H-10)
61.78
6.75–6.84 (para and meta proton of the Ph at C-4/C-10)
7.14–7.16 (ortho proton of the Ph at C-4/C-10)
7.29–7.32 (para proton of the Ph at C-8/C-9)
7.38–7.43 (meta proton of the Ph at C-8/C-9)
7.64–7.70 (ortho proton of the Ph at C-8/C-9)
125.95, 127.19, 127.22
127.85, 128.25
–
128.88, 128.91
126.81–127.07
127.19, 127.22, 128.88, 128.91, 138.89, 138.98
68.11, 70.26, 126.98, 127.07

Struct Chem
Fig. 7 Correlations between the
protons that are in BW^
arrangements, from the NOESY
spectrum of (4a)
rings in oximes were successfully achieved with the help of
half-with (W1/2) and NOESY analysis. The precursor 4,8,9,10-
tetraarylpiperidin-4-ones adopts twin-chair conformation with
the axial and equatorial orientation of aryl groups [33]. The
observed W1/2 of benzylic protons H-4 = 4.83 Hz and H-10 =
4.77 Hz are closely related to the parent ketone (H-4, 10 =
4.12 Hz). In the other benzylic protons, W1/2 of H-8 = 7.03
and H-8 = 5.92 Hz are also closely related to the ketone (H-8,
9 = 5.30 Hz). In the precursor, bridge-head protons (H-5, 7)
have strong NOESY correlation with the benzylic protons
(H-4, 8, 9, 10). The similar correlation occurring in oximes
and the bridged-head proton H-7 (δ 3.85 ppm) NOESY are
correlated with H-8 (δ 4.75 ppm) and H-10 (δ 4.60 ppm).
Besides, the piperidine nitrogen bridging CH2 group
NOESY correlation with H-4 and H-10 protons is also
similar to that of its precursor. Hence, these suggestions
confirm that the tricyclic oxime also adopts the twin-chair
conformation with axial and equatorial orientation of aryl
groups.
coupling (W arrangement). The W arrangement of stud-
ied compounds is shown in Fig. 7.
Oximation effect
The oximation effect of the two piperidine rings has been cal-
1
culated from H and 13C NMR chemical shift of oxime and
their respective parent ketones. In the studied oximes 4a-4e,
the proton chemical shift value of syn α-proton H-5 (Fig. 1) is
deshielded by 0.75 to 0.81 ppm and the anti-α-proton H-7
(Fig. 1) is shielded by 0.12 to 0.15 ppm. The benzylic protons
H-4, 10 are comparatively more shielded than other two ben-
zylic protons (H-8, 9). The shielding values of these protons
are shown in Table 6. This shielding effect confirms the oxime
group oriented in equatorial position (H-4, 10 proton side).
During oximation, the chemical shift value of N–CH2–N does
not produce any significant change. In general, in the decrease
in electronegativity of a particular group in the ring skeleton,
the α-carbon is more shielded and the β- and γ-carbons are
less shielded (Table 7) [33]. Accordingly, in oximes 4a-4d, the
carbon chemical shift value of syn α-carbon C-5 is shielded by
14–19 ppm and anti-α-carbon C-7 is shielded by 8–12 ppm.
The benzylic C-4 and C-10 carbons are also shielded. The
Long-range coupling in the saturated bicyclic and tri-
cyclic system occur through a rigid arrangement of the
bonds in the form of W (4J), with hydrogen occupying
the end position [30–32]. The strong correlation of the
NOESY spectrum implies the presence of long-range
Table 7 Effect of oximation on 13C chemical shifts (ppm) of 4a-4e
Table 6 Effect of oximation on 1H chemical shifts (ppm) of 4a-4e
Entry C2
C-4
C-5
C-7
C-8 C-9
C-10
δOxime–δKetone position
Entry
H-4
H-5
H-7
H8
H-9
H-10
δOxime–δKetone position
4a
4b
4c
− 0.05 − 2.47 − 18.94 − 12.84 0.84 − 1.31 − 3.75
− 0.07 − 2.50 − 18.94 − 12.84 0.81 − 1.35 − 3.71
− 0.09 − 2.58 − 19.08 − 12.79 0.76 − 1.41 − 3.82
− 0.05 − 2.38 − 18.90 − 12.83 0.75 − 1.39 − 3.69
4a
4b
4c
4d
4e
− 0.19
− 0.21
− 0.22
− 0.19
− 0.23
0.75
0.78
0.81
0.66
0.80
− 0.13
− 0.14
− 0.14
− 0.12
− 0.15
− 0.01
− 0.07
− 0.08
− 0.01
− 0.08
− 0.06
− 0.07
− 0.11
− 0.02
− 0.09
− 0.25
− 0.27
− 0.28
− 0.19
− 0.29
4d
4ea
4.62
2.08 − 14.45
− 8.14 5.53
3.25
0.81
a 13 C NMR spectrum of 4e is run by mixture of solvent (CDCl3 and DMSO)

Struct Chem
remaining 13C chemical shift values are compared with ketones
(2a-2d) and oximes (4a-4d) and listed in Table 7.
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014
Conclusion
In this study, a series of five new oximes of 4,8,9,10-tetraaryl-
1,3-diazaadamantan-6-one (4a-4e) were synthesized and char-
acterized by FT-IR, NMR spectral data to assign the structure
of the compounds. The chemical shift and conformation of the
compound are further confirmed by 2D NMR correlation of a
representative oxime 4a. On the basis of the H-1H COSY,
1
NOESY, and TOCSY spectral data, it is found that piperidine
rings exist in a twin-chair conformation with an axial orienta-
tion of the two aryl groups at C-4 and C-10 and equatorial
orientation of other two aryl groups (C-8 and C-9). In addi-
tion, the stereochemistry is not altered by the introduction of
an oxime group in the parent ketone. However, due to allylic
A strain in C=N–OH group and due to the proximity of the
oxime hydroxy and C5-H, the chemical shift values of C-5
and H-5 are shielded and deshielded respectively. The long-
range NOESY and TOCSY correlation further confirms the
structural framework of the oxime.
Acknowledgments The authors gratefully acknowledge DST- FIST
NMR facility of Department of Chemistry, The Gandhigram Rural
Institute-Deemed to be University for recording NMR spectra.
Funding information The authors thank the UGC, New Delhi, for Major
Research Project (grant No. 42-358/2013 (SR)) and UGC-Special
Assistance Programme (SAP).
Compliance with ethical standards
14. Choong IC, Ellman JA (1999) Synthesis of alkoxylamines by alk-
oxide amination with 3,3‘-Di-tert-butyloxaziridine. J Org Chem 64:
6528–6529. https://doi.org/10.1021/jo990490h
Conflict of interest The authors declare that they have no conflict of
interest.
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