Synthesis and rearrangement of N-methyl-N-(2-thiazolyl)-nitramine

Article abstract of DOI:10.1081/SCC-100105662

Methylation of N-(2-thiazolyl)-nitramine in alkaline solution gives 1,2-dihydro-3-methyl-2-nitriminothiazole which rearranges in concentrated sulphuric acid yielding small amount of 2-(N-methylamino)-5-nitrothiazole, identical with the product of rearrangement of N-methyl-N-(2-thiazolyl)-nitramine. The latter compound was obtained by the action of sodium hydride on 2-(N-methylamino)-thiazole followed by the nitration with n-butyl nitrate.

Full text of DOI:10.1081/SCC-100105662

This article was downloaded by: [Stony Brook University]
On: 25 October 2014, At: 06:34
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
SYNTHESIS AND REARRANGEMENT OF N-METHYL-N-
(
2-THIAZOLYL)-NITRAMINE
a a
a
Zdzisław Daszkiewicz , Monika Koterzyna & Janusz B. Kyzioł
a
Institute of Chemistry, Opole University , 45-052 Opole, ul., Oleska 48, Poland
Published online: 16 Aug 2006.
To cite this article: Zdzisław Daszkiewicz , Monika Koterzyna & Janusz B. Kyzioł (2001) SYNTHESIS AND REARRANGEMENT
OF N-METHYL-N-(2-THIAZOLYL)-NITRAMINE, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 31:19, 2921-2927, DOI: 10.1081/SCC-100105662
To link to this article: http://dx.doi.org/10.1081/SCC-100105662
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of
the Content. Any opinions and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied
upon and should be independently verified with primary sources of information. Taylor and Francis shall
not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other
liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 31(19), 2921–2927 (2001)
SYNTHESIS AND REARRANGEMENT
OF N-METHYL-N-(2-THIAZOLYL)-
NITRAMINE
Zdzislaw Daszkiewicz,* Monika Koterzyna,
and Janusz B. Kyziol
Institute of Chemistry, Opole University,
45-052 Opole, ul. Oleska 48, Poland
ABSTRACT
Methylation of N-(2-thiazolyl)-nitramine in alkaline solution
gives 1,2-dihydro-3-methyl-2-nitriminothiazole which rear-
ranges in concentratedsulphuric acidyiel di ng small amount
of 2-(N-methylamino)-5-nitrothiazole, identical with the
product of rearrangement of N-methyl-N-(2-thiazolyl)-nitr-
amine. The latter compoundwas obtainedby the action of
sodium hydride on 2-(N-methylamino)-thiazole followedby
the nitration with n-butyl nitrate.
Nitration of 2-amino thiazole in ca. 80% sulphuric acidgives the
ꢀ
primary nitramine 1 (m.p. 197–198 C) in moderate yield. Under influence
of the more concentratedaci d, it rearranges to 2-amino-5-nitrothiazole.
Methylation of 1 provides the N-methyl derivative, to which the structure
ꢀ
1
of N-methyl-N-(2-thiazolyl)-nitramine (2, m.p. 271.5–272 C) was assigned.
*
Corresponding author.
2
921
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
2
922
DASZKIEWICZ, KOTERZYNA, AND KYZIOL
The alleged secondary nitramine was used, as the model substrate, in the
2
investigations on mechanism of the nitramine rearrangement. Concomitant
1
rearrangement of the variously labelledcompound(CD and/or N-NO2)
5
3
did not give an answer for the question whether migration of the nitro group
from the nitrogen atom to the ring is inter- or intra-molecular. The authors’
conclusion that ‘‘the rearrangement is in part inter- andpart intra-molecular’’
is invalid. The experiments did not exclude the possibility that the tracer
exchange occurs in the substrate molecules, before the rearrangement.
Under proper conditions, the rearrangement consists of two separate steps,
which can be followedby the NMR spectrometry, hence it provi de s a rare
opportunity to register the spectra of an intermediate. The multinuclear
1
13
15
studies ( H, C and N) gave discrepant results. The proton NMR spectra of
the reaction mixtures detected one intermediate, in the carbon and nitrogen
NMR spectra, two distinct intermediates were observed. The nitronium
cation was not detected but, in spite of that, Toth et al. concluded that the
´
rearrangement involves the cleavage of the nitronium cation andits migration
2
to the N(3) andthen C(5) positions in the ring.
Due to our opinion, the nitramine rearrangement is an intramolecular
3
process. Susceptibility of a particular substrate to the rearrangement is
determined with the electronic properties of the migration terminus i.e. an
aromatic ring. Considering that the properties of the thiazole ring are inter-
mediate between those of the pyridine and benzene rings, one may expect
that the rearrangement of 2 can occur in a moderately concentrated sulphu-
ric acid. Moreover, this is well known that methylation of the primary
pyridylnitramines occurs at the cyclic nitrogen atom, yielding corresponding
4
nitrimines. We have assumedthat the compound eds cribedas the
N-methyl-N-(2-thiazolyl)-nitramine (2) is, in fact, 3-methyl-2-nitriminothia-
zoline (3) andhave made some attempts to prepare these compounds on two
independent ways.

ORDER
REPRINTS
N-(2-THIAZOLYL)-NITRAMINE
2923
We have foundthat N-(2-thiazolyl)-nitramine (1) reacts with dimethyl
sulphate, in an alkaline, aqueous solution in the same way as its pyridyl ana-
logues. The product 3 was obtainedin almost quantitative yield; after crysta-
ꢀ
llisation from DMF, it formedlight orange nee dl es melting at 275–280
with decomposition. The proton and carbon NMR spectra of 1 and 3 are
C
2
identical with those reported by Toth, unfortunately, the structures of 2 and
´
cannot be distinguished in this way. As shown by Kolehmainen et al., within
3
the pyridine series, the nitrimines and secondary nitramines give very similar
spectra, e.g. the resonances of the N-methyl group appear at 38–45 ppm,
5
irrespective of their position on the exo or endocyclic nitrogen atom.
2
-(N-Methylamino)-tiazole was obtainedaccor di ng to the previously
6
described procedure given on the scheme above. Formylation of 2-amino-
tiazole with an excess of n-butyl formate, in the presence of TFA, gave
2
1
1
ꢀ
-formamidothiazole (m.p. 164–165 C). The resonances at 8.53 and
2.2 ppm correspondto the formami od group. The carbonyl bandat
1
694 cm , the secondary and tertiary amide bands at 1564 and 1289 cm
ꢁ
ꢁ1
indicate that the formyl group is located at the exocyclic nitrogen atom.
Consequently, a liquid product obtained by the reduction with LAH must
be 2-(N-methylamino)-thiazole; its NMR, MS andIR spectra are in accor-
ꢀ
dance with that formula. The nitration was performed at ꢁ10 C, in 80%
sulphuric acid, using 100% excess of absolute nitric acid. The yield was low
due to the formation of 2-(N-methylamino)-5-nitrothiazole (4). The seco-
ndary nitramine 2 seems to be unstable under conditions required for its
formation. In more diluted mixed acid, the nitration did not occur and the
substrate was recoveredunchanged. We have obtaineda series of secondary
aromatic nitramines by nitration with n-butyl nitrate of the Grignardcom-
7
pound, prepared from an amine and ethylmagnesium bromide. This
methodis applicable to the nitration of 2-( N-methylamino)-thiazole, but
the yieldof 2 was unsatisfactory due to the low conversion. The method
of choice (ca. 60% yield, high purity) involves the action of sodium hydride
on 2-(N-methylamino)-thiazole in boiling benzene, followedby the nitration
with n-butyl nitrate.
ꢀ
The nitramine 2 forms colourless needles (m.p. 47–48 C from
n-hexane); its FTIR spectrum resembles closely the spectra of the other
8
secondary nitramines, with two bands at 1273 and 1537 cm , characteristic
ꢁ1

ORDER
REPRINTS
2
924
DASZKIEWICZ, KOTERZYNA, AND KYZIOL
of the N-nitro group. The nitrimine 3 displays in this region one strong band
ꢁ
1
at 1434 cm , corresponding to the stretching vibrations of the nitrimino
9
group. The NMR spectra of the compounds under discussion are collected
in Table 1.
The proton andcarbon spectra of 2 and 3 are different but indistin-
guishable, i.e. the chemical shifts of 3 can be assignedto 2 and vice versa.
Consequently, any attempt to identify the product of 1 methylation with
the aidof NMR spectroscopy may leadto the erroneous conclusion. The
isomers cannot be distinguished by the mass spectrometry as well. The most
abundant fragment ions are those at m/z 113 and69 in both spectra. The
expulsion of the NO radical is easier in the case of the nitramine 2, hence
2
the intensity of the molecular ion is much lower in the spectrum of 2. Such a
difference is not sufficient to recognize the structure of the N-methyl deri-
vative of N-(2-thiazolyl)-nitramine.
The secondary nitramine 2 appearedto be much more susceptible to the
thermally induced or acid catalysed rearrangement than its primary counter-
part 1 andN(3) substitutedisomer 3. The DSC/TGA analyses indicated that
ꢀ
1
mum on the DSC curve (50 C, melting) is well separatedfrom the maximum
decomposed violently at 205 C without melting. In the case of 2, the mini-
ꢀ
ꢀ
at 107 C corresponding to the rearrangement. The nitrimine 3 melts in the
ꢀ
ꢀ
crucible at 273 C, the onset of the rearrangement is observedat 276 C and
both endo and egzothermal effects are disturbed with the sublimation of the
substrate. We have carriedout the rearrangement of 2 in hot (110 C/5 h)
anisole andobtained 4 as the only isolable product; the yield was not high
ꢀ
Table 1. The NMR Spectra of Some Derivatives of 2-Aminothiazole (ca. 0.5 M
Solutions in DMSO-d
Standard)
6
(The Chemical Shifts d Are Given vs. TMS as the Internal
CompoundC-2
C-4, H-4
C-5, H-5
N-CH
105.9
6.54, d3.16, s
3
NH
2
1
2
3
4
-(N-NHMe)
170.4
170.3
157.6
167.3
173.3
139.0, 6.94,
d , J¼ 3.4 Hz
126.3, 7.66
d , J¼ 4.7 Hz
138.6, 7.70,
d , J¼ 3.8 Hz
131.2, 7.75
d , J¼ 4.4 Hz
147.4 8.27, s
31.2
–
7.30, s
112.8
7.30, d
5.14, s
118.0
7.60, d3.99, s
37.2
36.8
31.0
–
–
111.9
7.35, d3.70, s
135.1
9.29, s
2
.92, s

ORDER
REPRINTS
N-(2-THIAZOLYL)-NITRAMINE
2925
(
62%) but no other compound of defined structure can be detected in the
reaction mixture. The GCMS analyses confirmedthe lack of the products of
anisole nitration, hence the migration of the N-nitro group must have pro-
ceeded intramolecularly. The nitramine 2 rearranges readily to 4 in 80%
sulphuric acidat room temperature andalmost instantaneously in cold, con-
centrated acid; the yields are of the same order of magnitude as in the thermal
rearrangement (ca. 65%). We have performedthis transformation in the 20%
solution of sulphuric acidin the di oxane–water mixture (6:4, v/v) i.e. at the
acidity of H ¼ ꢁ0.65. This is well known that the nitronium cation can be
o
detected only in much more acidic solutions, hence the mechanism involving
de-nitration and re-nitration can be excluded in this case.
The nitrimine 3 is more resistant to 96% sulphuric acid, after 1 h at
room temperature, the substrate can be recoveredunchange d. We have
prolongedthe reaction time to 24 h andobtaineda multicomponent mix-
ture, from which 4 has been isolatedby the chromatographic techniques in
ca. 10% yield. 2-(N-Methylamino)-5-nitrothiazole forms yellow needles
ꢀ
2
ꢀ
melting at 227 C according to DSC (lit. m.p. 220–222 C). Its spectral
properties are consistent with this structure, e.g. in the IR spectrum, the bands
ꢁ
1
at 1504 and1380 cm
with the broadNH bandat 3215 cm
latedfrom the reaction mixture, were i ed ntifiedas
characteristic of the C-nitro group are accompanied
ꢁ
1
. Another products, which were iso-
N-methylurea and
elemental sulphur. Obviously, formation of 4 from 3 requires two
rearrangements, i.e. migration of the N-nitro and N-methyl groups hence,
at least two intermediates must be involved in the transformation. Their
structures cannot be deduced from the NMR data reported by Toth
´
2
et al., however their statement that the nitro group migrates as the free
nitronium cation seems to be reasonable. Consequently, 2,3-dihydro-
2-imino-3-methylthiazole, in its protonatedform, must be one of the
intermediates.
Considering that a simple migration of the N-methyl group, from one
nitrogen to another is impossible, it must be presumedthat the second
rearrangement involves ring opening andring closure via another, open
chain intermediate. Isolation of the products of decomposition of the thia-
zole ring (sulphur, urea) confirms the statement, however, the sequence

ORDER
REPRINTS
2
926
DASZKIEWICZ, KOTERZYNA, AND KYZIOL
of steps in the rearrangement is not clear at this stage of investigations. It
cannot be excluded that 4 is an artefact i.e. it is not formedin concentrated
sulphuric acid but it emerges during the neutralisation of the acidic solution
according to the ANRORC mechanism. Whatever is the mechanism, the
transformation of the nitrimine 3 into the amino–nitro compound 4 cannot
provide any relevant information on the mechanism of the nitro group
migration in the true nitramine rearrangement.
EXPERIMENTAL
2-Methylaminothiazole: To the intensely stirredsuspension of lithium
aluminium hydride (3.80 g, 0.10 mol) in absolute tetrahydrofuran (300 mL),
solid 2-formamidothiazole (12.80 g, 0.10 mol) was added in portions. The
mixture was stirredandrefluxedfor 2 h andcooledto room temperature.
Methanol (5 mL) and potassium hydroxide (12.0 g, as 50% aq. solution)
were cautiously added. A precipitate was filtered off, extracted with tetra-
hydrofuran and discarded. The solvent was evaporated, a residue was
dissolved in the ethyl ether–hexane mixture 1:1 and dried over anhydrous
magnesium sulphate. The solution was filtered, evaporated and the residue
ꢀ
was distilled in vacuum (75 C at 0.5 mmHg). 2-Methylaminothiazole (9.72 g,
þ
85%) was obtainedas a viscous, colourless liqui d. MS, m/z (int.): 114 (M ,
68), 113 (29), 99 (2), 86 (100), 58 (73), 57 (28), 55 (25). IR (CDCl ): 3455
3
(
N-H); 3156, 3127 (aromatic protons); 2991, 2933 (N-methyl group).
N-Methyl-N-(2-thiazolyl)-nitramine: 2-Methylaminothiazole (4.60 g,
0.04 mol), sodium hydride (3.20 g, 0.08 mol of 60% NaH) and benzene
(
250 mL) were stirredat the boiling point un de r nitrogen atmosphere for
2
0
h. The mixture was cooledto room temperature, n-butyl nitrate (10.00 g,
.08 mol) was added and the solution was stirred for 1 h. Water (20 mL) and
acetic acid (2 mL) were added and the layers were separated. The benzene
solution was extracted with aqueous (10%) sodium hydrogen sulphate
(
2 ꢂ 30 mL) andwater, and dr iedover anhy dr ous magnesium sulphate. The
solvent was evaporated under reduced pressure, the residue was dissolved in
n-hexane, stirredwith charcoal, filteredandcooledin a rd y-ice box.
N-Methyl-N-(2-thiazolyl)-nitramine (3.45 g, 59%) was collectedby filtration
ꢀ
þ
as light yellow prisms, m.p. 46–48 C. MS, m/z (int.): 159 (M , 10), 113 (94),
6 (3), 69 (100), 58 (15), 45 (29), 30 (14). IR (KBr): 1537, 1272 (stretching
vibrations of the N-nitro group).
-Methylamino-5-nitrothiazole:
1.60 g, 0.01 mol) was dissolved in the mixture of dioxane (23.00 g),
8
2
N-Methyl-N-(2-thiazolyl)-nitramine
(
water (15.10 g) and96% sulphuric acid(10.30 g). The mixture was main-
ꢀ
tainedat 40 C for 60 h, protectedfrom light. It was di lutedwith coldwater,

ORDER
REPRINTS
N-(2-THIAZOLYL)-NITRAMINE
2927
neutralisedwith potassium hy dr ogen sulphate andextracted(4
with methylene chloride. The extract was dried over anhydrous magnesium
sulphate, evaporatedandthe resi du e was crystallisedtwice from ethanol.
ꢂ20 mL)
2
-(N-Methylamino)-5-nitrothiazole was obtained(1.03 g, 64%), as yellow
ꢀ
þ
prisms melting at 222–223 C. MS, m/z (int.): 159 (M , 100), 143 (4), 129
7), 113 (94), 98 (42), 86 (40), 57 (36), 42 (14), 30 (9). IR (KBr): 3215 (proton
(
on heteroatom); 3100–2883 (hydrogen bond); 1612 (deformation of the NH
group); 1505 and1380 (stretching vibrations of the nitro group).
REFERENCES
1
2
. Dickey, J.B.; Towne, E.B.; Wright, G.F. J. Org. Chem. 1955, 20, 499;
Kasman, S.; Taurins, A. Can. J. Chem. 1956, 34, 1261.
. Nemes, A.; To
A.J.; Tamas, J.; Volford, J. Acta Chim. Hung. 1976, 88, 319.; To
Podanyi, B. J. Chem. Soc., Perkin 2 1984, 91.
. Daszkiewicz, Z.; Nowakowska, E.M.; Kyziol , J.B. Tetrahedron 1998,
4, 5991.
. Tschitschibabin, A.E.; Menschikov, G.P. Ber. Dtsch. Chem. Ges. 1925,
8, 406.
´
th, G. Acta Chim. Hung. 1975, 87, 257; To
´
th, G.; Nemes,
´
´
th, G.;
´
3
4
5
5
5
. Kolehmainen, E.; Laihia, K.; Kauppinen, R.; Gawinecki, R.; Rasala, D.
Magn. Res. Chem. 1993, 31, 659.
6
7
. Daszkiewicz, Z.; Doman
. Daszkiewicz, Z.; Doman
6, 337.
. Daszkiewicz, Z.; Nowakowska, E.; Prez
Chem. 1995, 69, 1437.
. Daszkiewicz, Z.; Kyziol, J.B.; Zaleski, J. J. Mol. Struct. 1999, 513, 69.
´
ski, A.; Kyziol, J.B. Chem. Papers 1993, 47, 109.
ski, A.; Kyziol, J.B. Org. Proc. Prep. Int. 1994,
´
2
8
9
`
do, W.W.; Kyzi o, lJ .B. Pol. J.
Receivedin the UK July 20, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC100105662