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Studies in tertiary amine oxides. III. Carbon-13 NMR assignment of N-alkynyl

cyclic amines.

Article in Organic Magnetic Resonance · January 1981

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 Studies in Tertiary Amine Oxides
IIIt-Carbon-13 NMR Assignment of N-Alkynyl Cyclic Amines

Jasim M. A. Al-Rawi and Abdul-Hussain Khuthier*

Department of Chemistry, College of Science, Mosul University, Mosul, Iraq

Carbon-13 NMR spectra of 24 N-alkynyl cyclic amines were analysed. The effect of substituting the
acetylenic proton by n-butyl, tert-butyl and phenyl groups was determined.

-
INTRODUCHON

A number of compounds containing both amino and

ethynyl functions have been reported to possess po-
tential pharmacological value. For example, a number
C N-CHzeC-R
1'

1
2' 3' 1'
N-CH,C=C-R

2
2' 3'

of N-(tert-aminoalkynyl) substituted-succinimides and

-2-pyrrolidones (Fig. 1) have been found to be potent
in blocking the motor effects of the muscarinic agent 1' 2' 3' C H 3 0 - C H 21' ~ 2'
( : -3' R
oxotremorine, N-(4-pyrrolidino-2-butynyl)-2-pyrrol-
idone.'
3 4

1' 2' 3'

Figure 1. N-(tert-arninoalkynyl) substituted-succinirnides and

-2-pyrrolidones. X=CH, or 6 0 ;n = 4-6; R,R = CH,, H.
'CH, CH, CH,
During our investigation of acetylenic tertiary amines
5 6
and their N-oxides' we synthesized a series of com-
pounds (Fig. 2) related to the above compounds. We
therefore report the I3C spectral data, not available in
the literature, for 24 compounds listed in Fig. 2. We
recently reported the 13C assignments for analogous
0
W
N-CH,C%C-R
1'

7
2' 3'

C 1'
N-CH,@C-R

8
2' 3'

compounds .3
CH,
4'1 5' 4' 5' 6' 7'
The assignments of the chemical shifts for the a R=-C-CH, b R = -CHzCH2CH2CH,
I
aceltylenic amines CH,

The I3C NMR spectrum of N-(4,4-dimethylpent-2-

yny1)piperidine (la) was assigned as in Table 1. Values
frorn 3,3-dimethyl- 1-butyne (Table 5 ) and compound
Id (Table 4) were used for the above assignments. The
R=G,f 9' 8'
d R=-H

assignment for the 13C signals in l b 8 b were made by

comparison with the chemical shifts of 2-heptyne4 and
Id (Table 4).3 Furthermore, assignments for the aryl
carbon atoms in lc-8c were obtained using values for
ethy nylbenzene' (13) (Table 5). Although the signals
for the acetylenic C-2' and C-3' (Table 3) were very
close (ii 85.1 and 85.2ppm, respectively) the distinc-
tion was readily made since C-2' showed a long range
coupling (t, 'JECH, = C-CH, = 8 Hz) .
*Part 11: See Ref. 3.
iAuthor to whom correspondence should be addressed
CCC-0030-4921/81/0015-0285$01.50
Figure 2. Some N-alkynyl cyclic arnines.
DISCUSSION
Replacement of the acetylenic proton with a methyl
group, i.e. CH,(CH,),C=C-H + CH3(CH2)3C=C-
CH, deshields the substituted carbon by +6.8ppm
(a effect) and shields the second s p carbon by -5.2
ppm ( p effect), while the y effect (first CH, carbon) is
deshielding by only +0.3ppm.4 On the other hand,
when the substituent is ethyl rather than methyl, the a,

@ Heyden & Son Ltd, 1981 ORGANIC MAGNETIC RESONANCE, VOL. 15, NO. 3, 1981 285
 J. M. A. AL-RAW1 AND A.-H. KHUTHIER

Table 1. Carbon-13 chemical shift assignments relative to TMS for substituted N-(4,4-
dimethylpent-2-ynyl) cyclic amines"
Compound
number c-2 c-3 C-4 C-5 C-6 c-1' c-2 c-3' C-4' c-5' c-7

la 53.4 26.1 24.2 26.1 53.4 48.2 73.6 93.6 27.5 31.3 -
2a 54.8 34.9 24.8 26.4 53.2 43.7 72.4 94.1 27.5 31.4 19.9
3a 60.8 31.3 32.6 25.5 52.7 47.8 73.5 93.7 27.4 31.3 19.8
4a 52.7 34.4 30.5 34.4 52.7 47.8 73.7 93.8 27.6 31.3 21.8
5a 54.7 35.5 25.5 35.5 54.7 37.5 71.5 94.0 27.6 31.6 20.9
6a 54.8 41.7 17.9 41.7 54.8 33.1 81.8 89.3 27.6 31.1 29.2
7a 52.4 66.9 - 66.9 52.4 47.7 72.8 94.4 27.5 31.3 -
8a 52.5 23.8 23.8 52.5 - 43.5 74.1 92.9 27.4 31.3 -

"The numbering of the carbon atoms corresponds with that in Fig. 2.

Table 2. Carbon-13 chemical shift assignments relative to TMS for substituted N-hept-2-ynyl cyclic amines"
Compound
number c-2 c-3 C4 c-5 C-6 c-7 c-1' c-2' C-3' C-4' c-5' C-W c-7
lb 53.5 26.1 14.2 26.1 53.5 - 48.2 75.2 85.1 18.2 31.1 22.0 13.7
26 54.8 35.0 24.8 26.5 53.4 20.1 43.8 74.3 85.2 18.5 31.3 22.0 13.7
3b 61.0 31.3 32.9 25.7 52.9 19.8 48.0 75.4 85.1 18.5 31.1 22.0 13.6
4b 52.9 34.5 30.6 34.5 52.9 21.9 47.9 75.5 85.0 18.5 31.1 22.0 13.7
5b 54.7 35.5 24.9 35.5 54.7 20.9 37.6 73.4 84.9 18.4 31.4 22.0 13.6
6b 55.0 41.4 18.8 41.4 55.0 27.5 33.4 80.7 83.2 18.0 31.3 22.1 13.6
7b 52.5 66.9 - 66.9 52.5 - 47.5 74.5 85.7 18.2 31.1 22.0 13.6
8b 52.7 23.9 23.9 52.7 - - 43.6 75.8 84.4 18.5 31.1 22.0 13.6
'The numbering of the carbon atoms corresponds with that in Fig. 2.

Table 3. Carbon-13 chemical shift assignments relative to TMS for substituted N-(3-phenylprop-2-ynyl) cyclic
amines"
Compound
number C-2 c-3 C-4 c-5 C-6 C-7 '2-1' C-2 C-3 C-4' c-5' C-B c-7'

lc 53.5 26.1 24.0 26.1 53.5 - 48.5 85.1 85.2 123.5 131.7 127.9 128.2
2c 54.9 34.9 24.7 26.5 53.6 20.1 44.1 84.3 85.4 124.3 131.8 128.2 127.9
3c 60.9 31.3 32.6 25.6 52.9 19.8 48.3 85.1 85.1 123.9 131.7 127.9 128.2
4c 53.0 34.4 30.4 34.4 53.0 21.8 48.2 85.1 85.2 123.5 131.8 128.2 128.0
5c 54.9 35.4 24.8 35.4 54.9 21 .o 38.1 83.6 85.1 123.7 131.9 128.8 127.8
6c 54.9 41.3 17.8 41.3 54.9 27.3 33.7 93.1 81.0 124.4 131.4 128.1 127.4
7~ 52.3 66.9 - 66.9 52.3 - 48.2 84.2 85.5 124.4 131.8 128.3 128.3
8~ 52.7 24.0 24.0 52.7 - - 43.9 85.5 84.5 123.6 131.8 128.0 128.3
"The numbering of the carbon atoms corresponds with that in Fig. 2.

p and y effects have values of + 13.6, -3.1 and + 1.3 of the substituted sp carbon (C-3') by 20.6-21.5 ppm
ppm, re~pectively.~ However, if the alkyl chain is ( a effect) and a shielding of the second s p carbon
increased further, e.g. by replacement of the acetylenic (C-2') by -5.5 ppm to -6.5 pprn ( p effect) while the
proton with n-propyl, n-butyl or n-heptyl, the a,P N-CH, carbon (C-1') was deshielded by only 0.2-0.6
and y effects become constant and have the values ppm ( y effect).
+ 11.4, -4.0 and +0.5 ppm, respectively. This is
consistent with the fact that the polarization effect falls Table 4. The 13C chemical shift assignments relative to TMS
off rapidly with an increasing number of (T bonds and for N-prop-2-ynyl cyclic aminesa
can be negligible through three bonds.6 Compou n d
Inspection of the data in Tables 2 and 4 reveals that number c-2 c-3 c-4 c-5 C-6 C-7 C-1' (2-2' C-3'

the replacement of the acetylenic proton in ld-8d by Id 53.2 26.0 24.0 26.0 53.2 - 47.7 79.3 72.9
2d 54.6 34.8 24.7 26.4 53.3 20.0 43.3 78.4 72.9
the n-butyl group (lb-8b) resulted in a deshielding of
3d 60.6 31.2 32.6 25.5 52.6 19.7 47.4 79.3 72.8
the first acetylenic carbon (C-3', Fig. 2) by between 4d 52.6 34.4 30.3 34.4 53.6 21.8 47.3 79.2 72.8
+12.1 and 12.4 ppm (a effect), a shielding of the !idb 54.6 35.4 24.8 35.4 54.6 20.9 37.3 77.6 72.5
second sp carbon (C-2') by -3.7 to -4.2ppm ( p 7d 52.2 66.7 - 66.7 52.2 - 47.1 78.6 73.6
effect) and a small deshielding for the N-CH, carbon Ed 52.4 23.9 23.9 52.4 - - 42.9 79.6 72.3
(C-1') by between 0.4-0.7 ppm ( y effect).
Similarly, Tables 1 and 4 indicate that the replace- aThe numbering of the carbon atoms corresponds with that in
Fig. 2.
ment of the acetylenic proton in compounds ld-8d by Compound 5d was prepared and assigned in a similar man-
a tertiary-butyl group (la-8a) results in a deshielding ner as compound I d (see Ref. 3).

286 ORGANIC MAGNETIC RESONANCE, VOL. 15, NO. 3, 1981 0Heyden & Son Ltd, 1981
 I3C NMR ASSIGNMENT OF N-ALKYNYL CYCLIC AMINES

Table 5. Carbon-13 chemical shifts of some substituted acetylenic compounds

and ol,b-effects'
Compound Molecular
number C-1 C-2 C-3 C-4 C-5 C-6 OL p structure
1 2
gb 71.8 71.8 - - - - - - H-CGC-H
1 2 3 4 5
10" 68.7 84 20.6 22.2 13.4 - 12.2 -3.1 HC&C-CH2CH2-CH3

1 2 3 /
11" 67.6 89.2 20.3 22.8 - - 17.2 -4.2 HCS-CH
\
CH3
EH3
1 2 3/
12d 66.8 92.6 27.4 31.1 - - 21.2 -5.1 HC=C-C-CH3
\
CH3
4 5

13" 77.8 84.0 122.7 132.4 128.6 120.4 12.2 +6.0 H b E 0 6

1 2
a The Q and p effects were calculated by subtraction of the values for H G C H from
the corresponding carbon shifts in compounds 10-13 respectively.
bSample 9 was prepared by bubbling acetylene gas into CDCI, at 5"C, TMS
was added and the spectrum was recorded at 25°C.
"The data for compounds 10, 11 and 13 were taken from Ref. 5, pp. 35, 36 and 2
without correction and the solvent was CCI,.
dThe '3C-chemical shift for compound 12 was recorded in CDCI, (15% w/v) with
internal TMS.

The (Y effect found in compounds la-8a is much EXPERIMENTAL

higher than that in compounds 1b-8b and this must be
due to branching in the alkyl chain attached to C-3'. A
similar branching effect on the I3C values for the
acetylenic carbon was found in 3,3-dimethyl-l-butyne
(12) as compared to acetylene (9) (Table 5).
If one compares the 13Cchemical shift values for the
two acetylenic carbon atoms in compounds 1 0 , l l and
12 (Table 5) it is revealed that the deshielding (a
effect) on the substituted s p carbon (C-2) is progres-
sively increased by 5 p p m per CH, substituent. The
second s p carbon (C-1) experiences a shielding ( p
effect) by 1 ppm per CH, substitution.
Inspection of the data in Tables 3 and 4 indicates
that the replacement of the acetylenic proton in com-
pounds ld-8d by a phenyl group (lc-8c) results in the
deshielding of C-3' by +11.9-+12.6 ppm (a effect)
while the other acetylenic C-2' carbon is also de-
shielded by +5.8-+6.1 ppm (6 effect). It is worth
noting that C-2' is shielded when the substituent is an
alkyl group. The deshielding effect in the phenyl sub-
stituted compounds is explained in terms of the con-
jugation of the acetylenic and phenyl IT systems.
Compounds la,b,c&a,b,c were synthesized by Man-
nich reaction of the appropriate substituted acetylene
and the secondary amines.' Compounds l b 8 d were
made by reaction of propargyl bromide and the ap-
propriate secondary amine.'" The synthesis and the
physical data of the above compounds will be pub-
lished elsewhere. 3,3-Dimethylbutyne is commercially
available (Fluka AG).
Spectra
The natural abundance I3C NMR proton noise-
decoupled and gated decoupled spectra were meas-
ured on a Bruker WH-90 DS F T NMR spectrometer
equipped with an ASPECT 2000, 32 K computer at a
magnetic field strength of 21 Kgauss. A pulse width
of 6 ps ( c . 30-40") was used with a 3 s pulse delay
time and 2000-4000 scans were accumulated with 8 K
data points for a spectral width of 6024Hz. The
samples were dissolved in CDC1, (15-25 by v/v) in a
10 mm 0.d. Wilmad NMR tube and a few drops of
TMS were added as internal reference.

REFERENCES

1. B. Karlen, B. Lindeke, S. Lindgren, K. G. Svensson, R.
Dehlbom, D. J. Jenden and J. E. Giering, J. Med. Chem. 13,
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2. (a) A.. H. Khuthier, M. A. Al-Iraqi, G. Hallstrom and B.
Lindeke, J. Chem. SOC. Chem. Commun. 9 (1979); (b) G.
Hallstrom, B. Lindeke, A. H. Khuthier and M. A. Al-Iraqi,
Tetrahedron Lett. 667 (1980).
3. M. A. Al-Iraqi, J. M. A. Al-Rawi and A. H. Khuthier, Org.
Magn. Reson. 14 (3), 161 (1980).
4. (a) Carbon-13 NMR Spectroscopy, J. B. Stothers, p. 87.
Academic Press, London (1972); (b) R. A. Friedel and H. L.
Retcofsky, J. Am. Chem. SOC.85, 1300 (1963).
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Kellerhals and J. T. Clerc, p. 2. Bruker (1976); (b) D. E.
Dorman, M. Jautelat and J. D. Roberts, J. Org. Chem. 38,
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Namikawa, J. Phys. Chem. 68,1956 (1964)
Received 3 January 1980; accepted (revised) 8 September 1980
@ Heyden & Son Ltd, 1981

@Heyden & Son Ltd, 1981 ORGANIC MAGNETIC RESONANCE, VOL. 15, NO. 3, 1981 287

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