Communication
utilized to synthesize cyclopentanone and ketones with
[
2c]
Abstract: 4,5-Dihydro-1,2,3-oxadiazoles are postulated to
be key intermediates in the industrial synthesis of ketones
from alkenes, in the alkylation of DNA in vivo, and in the
decomposition of N-nitrosoureas; they are also a subject
of great interest for theoretical chemists. In the presented
report, the formation of 4,5-dihydro-1,2,3-oxadiazole and
the subsequent decay into secondary products have been
studied by NMR monitoring analysis. The elusive proper-
ties evading characterization have now been confirmed
twelve-membered rings (30000 tons per year) by means of
1
,3-dipolar cycloaddition of N O to the alkene. Recently, Panov
2
[
2a,b]
et al. described
an alternative liquid-phase oxidation of cy-
clohexene and cyclopentene by nitrous oxide with nearly
00% selectivity. In these processes, 4,5-dihydro-1,2,3-oxadi-
1
azoles have been hypothesized to be intermediates that imme-
diately, under the reaction conditions, extrude dinitrogen to
give ketones in high yields. The use of N O in organic chemis-
2
try has been rather unexplored because of the relative chemi-
cal inertness and the high-energy input required. This low re-
activity can be overcome by utilizing reaction partners with
1
13
15
by H, C, and N NMR spectroscopy, and relevant 2D ex-
periments at very low temperatures. Our experiments
with suitably substituted N-nitrosoureas using thallium(I)
alkoxides as bases under apolar conditions answer impor-
tant questions on the existence and the secondary prod-
ucts of 4,5-dihydro-1,2,3-oxadiazole.
[
6]
[7]
ring strain, N-heterocyclic carbenes, or metalorganic re-
[
8]
[9,10]
agents. Quantum chemical calculations performed on 1
[
3,11]
and similar heterocycles
predict various secondary products
by different modes (Scheme 2), including the formation of di-
azomethane and formaldehyde as one of the most favorable
routes on the basis of inherent weakness of the NÀO bond.
On the other hand, the decomposition of suitably substitut-
ed N-nitrosoureas at physiological pH has also been postulat-
[1]
4
,5-Dihydro-1,2,3-oxadiazoles of type 1 are postulated to be
intermediates in the synthesis of ketones from alkenes under
[
2,3]
[4]
drastic conditions,
the decomposition of N-nitrosoureas at
ed to proceed via 1. In these cases, quantum chemical calcu-
lations likewise predict the intermediacy and the secondary
[
4]
physiological pH, and the alkylation of DNA and other rele-
[5]
[9]
vant molecules in vivo (Schemes 1 and 2). We became inter-
products of 1 (Scheme 2). The role of 3-methyl-4,5-dihydro-
ested in 1 from a process used by BASF Ludwigshafen wherein
1,2,3-oxadiazolium salts of type 2 in DNA alkylation and alkyl-
ation in general also suggests the transient formation of 1.
[
5]
N O (a waste product and highly potent greenhouse gas) is
2
There are reports on the methylation of nucleophilic com-
[
5a]
pounds by 2 in very good to moderate yields. In spite of
many discussions involving 2 as the methylating agent, no at-
tempts have been made to characterize 1 or its secondary
[
5]
products directly. However, contrary results with main or ex-
[2c]
Scheme 1. Industrial synthesis of cyclic ketones employed by BASF.
clusive nucleophilic attack at C-5 of 2 have also been publish-
[
5a,c,e,f,i,12]
ed.
Armed with such a great deal of information about the im-
portant role played by 1 in various branches of chemistry, we
present our results regarding to the existence and the forma-
tion of secondary products of 1.
Previous studies have been done on the decomposition of
[
4]
N-nitrosoureas in aqueous buffered solutions, but these con-
ditions are not conclusive to comment on the stability of
1
and the formation of its primary decay products. We chose
[
13]
thallium(I) alkoxides as bases, because of their high solubility
in various apolar solvents even at very low temperatures,
which is quintessential for monitoring the reaction by NMR
spectroscopy under such conditions. First, we utilized 2-chloro-
Scheme 2. Possible modes of formation and subsequent products of 1.
[
4d]
ethyl-N-nitrosourea (3) as a substrate to investigate the for-
mation of 1 in non-aqueous solutions (Scheme 3). Tosylate 4
was also synthesized for NMR studies, but it was not suitable
owing to its limited solubility in dichloromethane at low tem-
peratures. The generation of 1 was initially attempted by treat-
ing 3 with TlOEt (1.0 equiv) in CD Cl within the range À40 to
[
a] Prof. Dr. K. Banert, N. Singh
Organic Chemistry, Technische Universität Chemnitz
Strasse der Nationen 62, 09111 Chemnitz (Germany)
E-mail: klaus.banert@chemie.tu-chemnitz.de
Homepage: https://www.tu-chemnitz.de/chemie/org/index.html.en
[
b] B. Fiedler, Prof. Dr. J. Friedrich
2
2
[
14]
Theoretical Chemistry, Technische Universität Chemnitz
Strasse der Nationen 62, 09111 Chemnitz (Germany)
E-mail: joachim.friedrich@chemie.tu-chemnitz.de
À208C under constant monitoring by NMR spectroscopy. Im-
1
mediately, we could observe the H NMR signal of ethylene
oxide (15% yield) and traces of acetaldehyde along with
strong signals of 1-ethoxyethyl carbamate (5) (67% yield) and
a trace signal of diazomethane (Table 1). The identity of ethyl-
ene oxide and 5 was further confirmed by their chemical shift
[
c] M. Korb, Prof. Dr. H. Lang
Inorganic Chemistry, Technische Universität Chemnitz
0
9107 Chemnitz (Germany)
13
values in the C NMR spectrum. The observation of ethylene
Chem. Eur. J. 2015, 21, 15092 – 15099
15093 ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim