Gas-phase pyrolysis in organic synthesis: A route for synthesis of cyanamides

Article abstract of DOI:10.1002/jhet.217

(Chemical Equation Presented) Pyrolysis of 1,7-di-[(E)-1- morpholinomethylidene]- and 1,7-di-[(E)-1-piperidino-methylidene]-4,6,10,12- tetramethylamino-2,8-dioxo-1,7-diaza-3,5,9,11-cyclododecatetraene-3, 9-dicarbonitrile 6a,b afforded pyridone 10 in addition to cyanamides 11a,b. On the other hand, pyrolysis of 1-[E-(4-(E-3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)- ylimino) methylpiperazin-1-yl] methylenamino-4,6-dimethyl-2-oxo-1,2- dihydropyridine-3-carbonitrile 8 gave 1-amino-4,6-dimethyl-2-oxo-1,2- dihydropyridine-3-carbonitrile 13 as well as piperazine. The mechanism of pyrolysis and the effect of stereochemistry of pyrolyzed substrates on the nature of the pyrolysates are discussed.

Full text of DOI:10.1002/jhet.217

January 2010
Gas-Phase Pyrolysis in Organic Synthesis: A Route for
Synthesis of Cyanamides
207
a
Nouria A. Al-Awadi, * Mervat Mohammed Abdelkhalik,
b
a
Osman M. E. El-Dusouqui, and Mohammad H. Elnagdi
a
a
Chemistry Department, Kuwait University, Safat 13060, Kuwait
Applied Science Department, College of Technological Studies, Public Authority for
Applied Education and Training, Kuwait
b
*
E-mail: n.alawadi@ku.edu.kw
Received January 18, 2007
DOI 10.1002/jhet.217
Published online 21 December 2009 in Wiley InterScience (www.interscience.wiley.com).
Pyrolysis of 1,7-di-[(E)-1-morpholinomethylidene]- and 1,7-di-[(E)-1-piperidino-methylidene]-
6a,b
4
,6,10,12-tetramethylamino-2,8-dioxo-1,7-diaza-3,5,9,11-cyclododecatetraene-3,9-dicarbonitrile
afforded pyridone 10 in addition to cyanamides 11a,b. On the other hand, pyrolysis of 1-[E-(4-(E-3-
cyano-4,6-dimethyl-2-oxopyridin-1(2H)-ylimino) methylpiperazin-1-yl] methylenamino-4,6-dimethyl-2-
oxo-1,2-dihydropyridine-3-carbonitrile 8 gave 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-car-
bonitrile 13 as well as piperazine. The mechanism of pyrolysis and the effect of stereochemistry of
pyrolyzed substrates on the nature of the pyrolysates are discussed.
J. Heterocyclic Chem., 47, 207 (2010).
INTRODUCTION
zide in the presence of diethylamine gave a dimeric
þ.
product 4 of m/z ¼ 327 (M þ 1) [7]. Here, the reaction
N-Aminoheteroaromatics are readily obtainable pre-
cursors [1–5]. The amino function could then be con-
densed with aromatic aldehydes into 1. The gas-phase
pyrolysis of this derivative produces pyridones 2 and
nitriles 3 [6,7]. This approach offers an ideal and envi-
ronmentally friendly methodology for synthesis of
nitriles and related compounds, as no reagents, solvents,
or catalysts are used in these thermal gas-phase reac-
tions [8]. It seemed to us quite feasible that simple alter-
nation in the structure of starting substrates could also
be adopted as a strategy to synthesize cyanamides as
well as organic cyanates (Scheme 1).
of the dimeric product 4 with triethylorthoformate
afforded the diiminoformate 5, which is then converted
into 6a,b and 8 through reaction with secondary amines,
namely, morpholine, piperidine, and piperazine. Com-
pound 5 could as well be generated in situ in a one-pot
synthesis by mixing the three products under reflux in
N,N-dimethylformamide. The reaction is facile, clean,
and efficient, and is free from by-products. The struc-
tural assignments of compounds 5–8 were inferred from
their mass spectra and other analytical data. Formation
of 8 is believed to occur via initial conversion of diimi-
noformate 5 to the intermediate iminoformate 7 and sub-
sequent condensation of two molecules of 7 with one
molecule of piperazine (Scheme 2).
RESULTS AND DISCUSSION
Pyrolysing 6a,b in the gas phase gave the expected
1,2-dihydropyridine-3-carbonitrile derivative 10 and cy-
anamide 11a,b via the methyleneamino-1,2-dihydropyri-
dine-3-carbonitrile derivative 9 (Scheme 3). Formation
of these products was confirmed by LCMS and by TLC,
In the present article, we report synthesis of different
substituted 1,7-diaza-3,5,9,11-cyclododecatetraene deriv-
atives 4 as well as the results of their pyrolysis in the
gas phase. In a recent investigation, we established that
the reaction of acetylacetone with 2-cyanoacetohydra-
1
as well as H NMR of products of pyrolysis against
V
C
2009 HeteroCorporation

2
08
N. A. Al-Awadi, M. M. Abdelkhalik, O. M. E. El-Dusouqui, and M. H. Elnagdi
Vol 47
Scheme 1
Scheme 3
authentic specimens of pyridone 10. On the other hand,
pyrolysis of 8 afforded 13 without formation of 12
route required the use of hazardous and explosive cya-
nogen bromide reagents.
(Scheme 4).
The difference in the pyrolytic behavior of 6a,b and 8
is most likely a result of their stereochemistry. Thus, the
pyrolyzed compounds 6a,b exist in the (E) form, while
EXPERIMENTAL
Melting points were determined on a Shimadzu-Gallenkamp
apparatus and are uncorrected. Elemental analysis was by
means of a LECO CHNS-932 Elemental Analyzer. NMR spec-
tra were measured using a Bruker DPX 400 MHz supercon-
ducting spectrometer, and FT-IR measurements were from a
Perkin Elmer 2000 FT-IR system. Mass spectrometric analysis
was carried out on a VG-Autospec-Q high performance tri-sec-
tor GC/MS/MS, and the instrument for HPLC was an Agilent
1100 series LC/MSD with an API-ES/APCI ionization mode.
1,7-Diamino-4,6,10,12-tetramethyl-2,8-dioxo-1,7-diazacyclo-
dodeca-3,5,9,11-tetraene-3,9-dicarbonitrile 4. This compound
was prepared following published procedure. It was obtained
8
exists in the (Z) form. If one assumes that the pyroly-
sis of 8 (E) occurred via the H-bonded intermediate
Scheme 3), one would obtain pyridine 10 and dicyana-
mide 12 as pyrolytic products. As the N-aminopyridone
3 was the pyrolytic product obtained from 8 and no
(
1
trace of the dicyanamide 12 was detected, it can thus be
expected that 8 exists in the non-H-bonded (Z) form. In
fact here, hydrolysis of 8 under the pyrolytic reaction
conditions took place. To our knowledge such a hydro-
lysis has not been reported earlier. In conclusion, we
could determine structures of pyrolysis products of 6a,b
and 8. In addition, a new and safe route for synthesis of
cyanamide 11a,b is reported. Although 11a,b could be
obtained by treating cyanogen bromide with Mannich
bases [9] and with morpholine compounds [10,11], this
ꢀ
as white crystals from ethanol (yield 94%); m.p. 171–172 C,
ꢁ1
ꢀ
2
Lit. mp. 174 C [7]; IR (KBr): k max/cm : 3420, 3332 (NH ),
þ.
1
and 2216 (CN); MS: m/z ¼ 327 (M þ1). H NMR (DMSO):
d ¼ 2.31 (s, 6H, 2CH ), 2.42 (s, 6H, 2CH ), 6.15 (br s, 4H,
3
3
2NH D O exchangeable), 6.33 (s, 2H). Anal. Calcd. for
2
2
C
5
16
H
18
N
6
O
2
(326.36): C 58.89, H 5.56, N 25.75. Found C
9.00, H 5.49, N 25.89.
,6,10,12-Tetramethyl-1,7-(diethoxy-dimethylene-amino)-
,8-dioxo-1,7-diaza-3,5,9,11-cyclododeca-tetraene-3,9-dicar-
4
2
Scheme 2
bonitrile 5. To a stirred mixture of compound 4 (0.01 mol,
.26g) in 10 mL of N,N-dimethylformamide was added triethyl
3
orthoformate (0.01 mol, 1.48 g). The resulted mixture was
refluxed for 15 min. The solvent was removed and resulting
solid was recrystallized from ethanol. Yield 86% (3.77g); m.p.
ꢀ
ꢁ1
1
50 C; IR (KBr): k max/cm : 2218 (CN), 1658 (C ¼¼ O); MS:
þ.
1
m/z ¼ 439 (M þ 1); H NMR (DMSO): d ¼ 1.35 (t, 6H, J ¼
7
.04 Hz 2CH ), 2.28 (s, 6H, 2CH ), 2.33 (s, 6H, 2CH ), 4.35
3
3
3
Scheme 4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
Gas-Phase Pyrolysis in Organic Synthesis: A Route for Synthesis of Cyanamides
209
þ.
(
q, 4H, J ¼ 7.04 Hz 2CH
2
), 6.37 (s, 2H, cycloalkene-H), 8.36
(438.49): C
0.26, H 5.98, N 19.17. Found C 60.06, H 5.94, N 19.25.
Piperidine-1-carbonitrile 11b. MS: m/z ¼ 110 (M ) for
1
(
s, 2H, amidine-H). Anal. Calcd. for C22
H
26
N
6
O
4
C H N (110.16). H NMR (CDCl ): d (ppm) ¼ 1.41–1.52
6
10
2
3
6
(m, 6H, piperidinyl-H), 3.56–3.78 (m, 4H, piperidinyl-H). Lit
H NMR 90 MHz (CDCl ) [13]: d (ppm) ¼ 1.45–1.68 (m,
1
General procedure for the preparation of compounds
a,b and 8. To a stirred mixture of compound 5 (0.01 mol,
.38 g) in 20 mL of DMF was added the appropriate amine
3
6
4
(
6H), 3.2–3.5 (m, 4H)].
4,6-Dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile
þ.
1
0.01 mol). The mixture thus obtained was heated under reflux
10. MS: m/z ¼ 163 (M ) for C H N O (148.16). H NMR
8
8 2
for 20 hours. The solvent was removed and the resulting solid
was recrystallized from DMF.
4,6,10,12-Tetramethyl-1,7-di-[(E)-1-morpholino-methylidene]
amino-2,8-dioxo-1,7-diaza-3,5,9,11-cyclododecatetraene-3,9-
dicarbonitrile 6a. Yield 85% (4.42 g); m.p. 190 C, brown
crystals from DMF; IR (KBr): m/cm : 2216 (CN), 1647
(CDCl ): d (ppm) ¼ 2.33 (s, 3H, CH ), 2.40 (s, 2H, CH ),
3 3 3
3.60 (br s, 1H, NH D O exchangeable), 6.21 (s, 1H, pyridyl
2
1
H-5). [Lit H NMR 200 MHz (DMSO/CDCl3 2:1 [14]): d
1( pHp )m] .) ¼ 2.23 (s, 3H), 2.32 (s, 3H), 3.40 (br s, 1H), 6.07 (s,
1-Amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbo-
ꢀ
ꢁ
1
þ.
1
þ.
1
(
(
(
C ¼¼ O); MS: m/z ¼ 521 (M þ 1); H NMR (DMSO-d ): d
8 9 3
nitrile 13. MS: m/z ¼ 163 (M ) for C H N O (163.18).
H
6
ppm) ¼ 2.26 (s, 6H, 2CH ), 2.30 (s, 6H, 2CH ), 3.50–3.54
NMR (CDCl ): d (ppm) ¼ 2.33 (s, 3H, CH ), 2.38 (s, 2H,
3
3
3
3
m, 8H, morpholino-H), 3.62–3.65 (m, 8H, morpholino-H),
CH ), 6.15 (br s, 4H, 2NH D O exchangeable), 6.31 (s, 1H,
3
2
2
6
Calcd. for C H N O (520.59): C 59.99, H 6.20, N 21.52.
.30 (s, 2H, cycloalkene-H), 7.93 (s, 2H, amidine-H). Anal.
pyridyl H-5).
26 32 8 4
Found C 60.06, H 6.26, N 21.58.
,6,10,12-Tetramethyl-2,8-dioxo-1,7-di-[(E)-1-piperidinome-
thylidene]amino-1,7-diaza-3,5,9,11-cyclododecatetraene-3,9-
Acknowledgment. The support of the University of Kuwait
received through research grant (SC02/03) and the facilities of
Analab/SAF (GS02/01, GS03/01) are gratefully acknowledged.
4
ꢀ
dicarbonitrile 6b. Yield 92% (4.75 g); m.p. 115 C, brownish
ꢁ
1
crystals from ethanol; IR (KBr): m/cm : 2213 (CN), 1652
þ.
1
(
(
C ¼¼ O); MS: m/z ¼ 517 (M þ1); H NMR (DMSO-d ): d
6
ppm) ¼ 1.50–1.57 (m, 8H, piperidinyl-H), 1.63–1.66 (m, 4H,
REFERENCES AND NOTES
3 3
piperidinyl-H), 2.25 (s, 6H, 2CH ), 2.29 (s, 6H, 2CH ), 3.29–
3
6
.31(m, 4H, piperidinyl-H), 3.48–3.52 (m, 4H, piperidinyl-H),
.26 (s, 2H, cycloalkene-H), 7.81 (s, 2H, amidine-H). Anal.
[
1] Al-Awadi, N. A.; Ibrahim, Y. A.; Dib, H. H.; Ibrahim, M.
R.; George, B. J.; Abdallah, M. R. Tetrahedron 2006, 62, 6214.
2] Kandari, H.; Al-Kharafi, F. N.; Al-Awadi, A.; El-Dusouqui,
O. M. E. S.; Ali, A.; Katrib, A. Appl Catal A: Gen 2005, 295, 1.
3] Al-Etaibi, A. M.; Abdallah, M. R.; Al-Awadi, N. A.;
Ibrahim, Y. A.; Hassan, M. J Phys. Org. Chem 2004, 17, 49.
4] Alnajjar, A.; Amer, S. A.; Riad, R. M.; Elghamry, I.;
Calcd. for C H N O (516.65): C 65.09, H 7.02, N 21.69.
Found C 64.67, H 6.71, N 21.57.
,1’-{Piperazine-1,4-diylbis[(Z)-methylylidenenitrilo]} bis
28 36 8 2
[
1
4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile 8. Yield
[
(
ꢀ
6
2% (2.67 g); m.p. >300 C, buff crystals from DMF; IR
[
ꢁ
1
(
(
2
3
8
KBr): m/cm : 2217 (CN), 1642 (C ¼¼ O); MS: m/z ¼ 433
Elnagdi, M. H. J Chem Res (S) 1996, 296.
þ.
1
M þ1); H NMR (DMSO-d
6
): d (ppm) ¼ 2.29 (s, 6H,
[5] Gilchrist, T. L. Heterocyclic Chemistry, 3rd ed.; Addison
Wesely Longman: Harlow, 1997; p 138.
3 3
CH ), 2.31 (s, 6H, CH ), 3.44–3.48 (m, 4H, piperidinyl-H),
.57–3.64 (m, 4H, piperidinyl-H), 6.30 (s, 2H, pyridyl H-5),
.00 (s, 2H, amidine-H). Anal. Calcd. for C H N O
2 24 8 2
[6] Al-Awadi, N. A.; Elnagdi, M. H.; Mathew, T.; Elghamry,
I.; Abdelkhalik, M. M. Int J Chem Kinet 1996, 28, 741.
2
[
7] Al-Awadi, N. A.; Abdelkhalik, M. M.; Patel, M.; Dib, H.
H. J Heterocyclic Chem 2007, 44, 989.
8] Malhas, R. N.; Al-Awadi, N. A.; El-Dusouqui, O. M. E. Int
(
2
432.48): C 61.10, H 5.59, N 25.91. Found C 60.69, H 5.72, N
5.68.
General Procedure for Pyrolysis of 6a,b and 8. Each of
compounds 6a–c and 8 was introduced in the reaction tube
[
J Chem Kinet 2007, 39, 82.
2
[9] Martin, D.; Weise, A. Chem Ber 1966, 99, 3367.
(
1.5 ꢂ 12 cm Pyrex), cooled in liquid nitrogen, sealed under
[
10] Henry, R. M.; Dehn, W. M. J Am Chem Soc 1950, 72,
vacuum (0.06 mbar) and placed in the pyrolyser for 900 s at a
temperature of complete pyrolysis. The pyrolysate was then
separated into its constituents by preparative TLC (MERCK,
2
7
280–1.
[
11] Wishnok, J. S.; Tannenbaum, S. R. Anal Chem 1977, 49,
15A–6A.
2
1
2 PSC-Platten 20 ꢂ 20 cm , Silica gel 60 F
2 mm) using
54
2
[
12] SciFinder, CAS Register Number: 1530–87-6. Source: Inte-
chloroform: petroleum ether (bp 40:60) in 80:20 ratio as elu-
ent, and each constituent was collected, analyzed and charac-
1
terized. The techniques used include H NMR and GC/MS.
grated Spectral Database System of Organic Compunds. Data were
obtained from the National Institute of Advanced Industrial Science
and Technology, Japan.
þ.
Morpholine-4-carbonitrile 11a. MS: m/z ¼ 112 (M ) for
[
13] SciFinder, CAS Register Number: 1530–89-8. Source: Inte-
ꢁ
1
1
C H N O (112.13). IR ¼ 2220 cm (CN). H NMR (CDCl ):
5
8
2
3
grated Spectral Database System of Organic Compunds. Data were
obtained from the National Institute of Advanced Industrial Science
and Technology, Japan.
d (ppm) ¼ 3.05–3.08 (m, 2H, morpholinyl-H), 3.21–3.23 (m,
2
3
H, morpholinyl-H), 3.43–3.49 (m, 2H, morpholinyl-H), 3.59–
)
1
.68 (m, 2H, morpholinyl-H). [Lit H NMR 90 MHz (CDCl
3
[14] Alberola, A.; Andr e´ s, C.; Ortega, A. G.; Pedross, R.;
Vicente, M. J Heterocyclic Chem 1987, 24, 709.
[
12]: d (ppm) ¼ 3.2–3.3 (m, 4H), 3.6–3.7 (m, 4H)].
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet