Viability of 4,5-dihydro-1,2,3,4-oxatriazoles reinvestigated

Article abstract of DOI:10.1002/chem.201100231

The first procedures to prepare 4-bromo-4-methylpentanal and 4-azido-4-methylpentanal are reported. The latter compound and also the parent 4-azidobutanal do not lead to 4,5-dihydro-1,2,3,4-oxatriazoles by intramolecular 1,3-dipolar cycloaddition, although it was claimed to be so in the literature. The NMR spectroscopic data of such heterocycles reported previously do not agree with those of similar substances and are incompatible with ¹³C NMR spectroscopic chemical shifts calculated by quantum chemical methods in the presented work. These calculations show furthermore that the intramolecular cycloaddition of 4-azidobutanals to give the title compounds is strongly endothermic and thus most probably not possible.

Full text of DOI:10.1002/chem.201100231

FULL PAPER
DOI: 10.1002/chem.201100231
Viability of 4,5-Dihydro-1,2,3,4-oxatriazoles Reinvestigated**
Samia Firdous,[a] Klaus Banert,*[a] and Alexander A. Auer*[b]
Abstract: The first procedures to pre-
data of such heterocycles reported pre-
viously do not agree with those of simi-
lar substances and are incompatible
with 13C NMR spectroscopic chemical
pare 4-bromo-4-methylpentanal and 4-
azido-4-methylpentanal are reported.
The latter compound and also the
parent 4-azidobutanal do not lead to
4,5-dihydro-1,2,3,4-oxatriazoles by in-
tramolecular 1,3-dipolar cycloaddition,
although it was claimed to be so in the
literature. The NMR spectroscopic
shifts calculated by quantum chemical
methods in the presented work. These
calculations show furthermore that the
intramolecular cycloaddition of 4-azi-
dobutanals to give the title compounds
is strongly endothermic and thus most
probably not possible.
Keywords: azides · cycloaddition ·
nitrogen heterocycles · NMR spec-
troscopy · quantum chemistry
Introduction
A great proportion of all organic compounds belong to the
class of heterocycles, which includes fundamental groups of
natural products as well as biologically and pharmaceutically
active substances. In particular, compounds that bear nitro-
gen and/or oxygen atoms in five-membered rings are highly
important targets, and the synthesis of the first examples of
such a new heterocyclic system obviously deserves especial
interest. In 2002, Yuan Ma reported on the products 3a,b
prepared in good yields (85–89%) by treating the precursors
1a,b or 1c, respectively, with sodium azide in DMF at 508C
(Scheme 1).[1] The formation of heterocycles 3a,b was ex-
plained by a reaction sequence of nucleophilic substitution
followed by intramolecular 1,3-dipolar cycloaddition. Thus,
it was claimed that the reaction of 1a with sodium azide at
08C led to the intermediate 2a, which could be converted
into 3a on heating at 508C. Since compounds 3a,b represent
the first and only examples of 4,5-dihydro-1,2,3,4-oxatria-
zoles, the results reported in 2002 were cited and reviewed
repeatedly.[2]
[a] S. Firdous, Prof. Dr. K. Banert
Organic Chemistry, Chemnitz University of Technology
Strasse der Nationen 62, 09111 Chemnitz (Germany)
Fax : (+49)371-531-21229
Scheme 1. Intramolecular cycloaddition and cyclization reactions of
azides.
E-mail: klaus.banert@chemie.tu-chemnitz.de
[b] Prof. Dr. A. A. Auer
Max-Planck-Institut fꢀr Eisenforschung GmbH
Max-Planck-Strasse 1, 40237 Dꢀsseldorf (Germany)
Fax : (+49)211-6792-218
The well-known[3] transformation of 4a and 4b into 5a,b
and 5c, respectively, seems to be similar to the formation of
3a,b from 2a,b. However, the question arises whether the
carbonyl group of an aldehyde and an azido unit are ther-
modynamically more favorable than a nonaromatic 4,5-dihy-
E-mail: auer@mpie.de
[**] Reactions of Unsaturated Azides, Part 26; for Part 25, see: K.
Banert, B. Meier, E. Penk, B. Saha, E.-U. Wꢀrthwein, S. Grimme, T.
Rꢀffer, D. Schaarschmidt, H. Lang, Chem. Eur. J. 2011, 17, 1128–
1136.
ꢀ
dro-1,2,3,4-oxatriazole that includes a weak O N single
bond. If an azido and carbonyl group result in a conjugated
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100231.
Chem. Eur. J. 2011, 17, 5539 – 5543
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5539

system, as shown in the case of acyl azides 6, it is well-docu-
mented that open-chain 6 is thermodynamically more stable
than aromatic 1,2,3,4-oxatriazole 7.[2a,4] On the other hand,
the ring closure of vinyl azides 8 to give 4H-1,2,3-triazoles 9,
which can tautomerize to produce aromatic 1,2,3-triazoles,
may be an exothermic process. Nevertheless, the transforma-
tion 8!9 is rarely observed,[5,6a] because loss of dinitrogen
and formation of 2H-azirines 10 proved to be a more gener-
al reaction of 8.[6,7]
formed. The same result was observed after prolonged heat-
ing at 808C; slow decomposition of 2a was noticed at 908C.
The bromide 1a is known to be unstable.[8] We found that
the trimer 11a was generated on heating of neat 1a. In a
clean reaction, storing 1a for three weeks at ꢀ25 to ꢀ308C
led to 11a in 87% yield. The analogous transformation of
1b gave the heterocyclic product 11b with 89% yield. At
508C, but not at 08C or room temperature, 11a or 11b were
converted into 11c in the presence of sodium azide in DMF.
Each of the 1,3,5-trioxanes 11 was formed as a single diaste-
reomer, most probably, with all-cis configuration, which is
quite normal in the case of aldehyde trimerization.[10] The
1H and 13C NMR spectroscopic data, reported for 3a in
2002,[1] are identical with our data of 11a but differ signifi-
cantly from those of 11c. Thus, we assume that 11a was
taken erroneously for 3a and something was confused with
these compounds.[1]
When the NMR spectroscopic data given previously for
3a,b[1] were compared with those of 5a–c,[3] we had to call in
question the substructures of 4,5-dihydro-1,2,3,4-oxatria-
1
zoles. Whereas 6-H of 5a resulted in an H NMR spectro-
scopic signal with d=4.34 ppm,[3b] 5-H of 3a was claimed to
resonate at d=3.44 ppm.[1] Even greater contradictions were
found in the case of 13C NMR spectroscopic data: C-6 of 5a
and 5b showed signals in the range d=57–60 ppm, and the
corresponding signal of 5c was found at d=64.9 ppm,[3b]
whereas only signals in the interval d=26–34 ppm can be as-
signed to C-5 of 3a,b based on the reported data.[1] Further-
more, the folded structure of 5 led to CH2 groups with dia-
stereotopic protons (2J=16.5 Hz) and to diastereotopic
methyl groups in the case of 5c.[3b] This should also be true
for 3a,b. But no hints on diastereotopic protons or methyl
groups were given, and 3b was characterized by five instead
of six 13C NMR spectroscopic signals.[1]
No data for 1c or hints how to prepare this bromide,
which is not mentioned elsewhere in literature, were given
in the previous work.[1] We tried several routes to synthesize
1c, all of which were unsuccessful (for example, treatment
of unsaturated aldehyde 13[11] with hydrogen bromide;
Scheme 3). Finally, we found that ozonolysis of olefinic bro-
These discrepancies encouraged us to repeat treatment of
1a–c with sodium azide in DMF to clarify whether 4,5-dihy-
dro-1,2,3,4-oxatriazoles 3a,b are formed. Herein, we report
that the latter heterocycles cannot be prepared from 1a–c
and, most probably, cannot be generated at all. These con-
clusions are not only based on our experimental work but
also strongly supported by quantum chemical calculations
presented in the following.
Results and Discussion
We synthesized azide 2a by treating 1a[8] or 1b[9] with
sodium azide in DMF at 508C (Scheme 2). However, under
these conditions and also on heating 2a with or without
sodium azide at 508C, no heterocyclic product 3a was
Scheme 3. Synthesis of bromide 1c and azide 2b.
mide 12[12] gave the target compound 1c in low yield as a
highly unstable light-yellow liquid that could be character-
1
ized by IR, H, and 13C NMR spectroscopy for the first time.
The reaction of 1c with sodium azide in DMF did not lead
to the substitution product 2b or the heterocycle 3b since
decomposition of the starting material was observed. At-
tempts to prepare 2b by electrophilic addition of hydrazoic
acid to 13 in the absence or presence of p-toluenesulfonic
acid were also unsuccessful. However, treatment of the alco-
hol 14[13] with hydrazoic acid in the presence of 4-methyl-
benzenesulfonic acid gave an improved yield of the unsatu-
rated azide 4b, which afforded the desired product 2b by di-
hydroxylation followed by oxidative cleavage of the result-
ing diol 15. The g-azido aldehyde 2b proved to be a stable
compound that could not be converted into 3b by prolonged
Scheme 2. Reactions of 4-functionalized butanals.
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Chem. Eur. J. 2011, 17, 5539 – 5543

4,5-Dihydro-1,2,3,4-oxatriazoles
FULL PAPER
heating at 508C. This negative result was also found at
808C, whereas slow decomposition was observed on expos-
ing a solution of 2b in DMF at 908C.
tion of the 13C NMR spectroscopic chemical shifts shows
good agreement with the values measured for 5a and 5b;
however, the values calculated for 3a do indeed give a
signal at d=56 ppm, which is absent in the data set report-
ed[1] previously (Table 2).
To support our findings, calculations using DFT and
Møller–Plesset perturbation theory were carried out for sys-
tems 2a, 3a, 4a, 5a, and 5b. Minimum geometries of prod-
ucts and educts as well as transition states were optimized
to gain insight into the energetics of the two types of intra-
molecular 1,3-dipolar cycloaddition reactions, and the
13C NMR spectroscopic chemical shifts of species in question
were calculated.
Table 2. Experimental[a] and calculated[b] 13C NMR spectroscopic data of
compounds 2a, 3a, 4a,b, 5a,b,c, and 11a.
Compound d [ppm]
2a
21.2, 29.8 (C-3), 40.5, 42.6 (C-2), 50.3, 58.2 (C-4), 200.8,
213.9 (C-1)
26.8, 32.9, 33.5, 100.4; 25.3 (C-6), 36.0 (C-7), 55.9 (C-5), 98.8
(C-8)
19.4, 18.6 (C-6), 30.2, 39.5 (C-3), 35.3, 43.0 (C-4), 57.2, 67.1
(C-5), 115.3, 122.2 (C-1), 137.4, 151.2 (C-2)
26.0 (Me), 28.5 (C-3), 40.5 (C-4), 61.3 (C-5), 114.7 (C-1),
138.0 (C-2)
3a[c]
4a
From the results of the quantum chemical calculations
(Table 1), it becomes clear that although the reactions of 4a
to form 5a and 5b are exothermic and the products stable
4b
Table 1. Calculated relative energies [kJmolꢀ1] including zero-point vi-
brational energies calculated at the B3-LYP/QZVP level of theory.
5a
21.7, 25.9 (Me), 30.0, 35.4 (C-4), 31.7, 38.3 (C-5), 56.8, 64.9
(C-3a), 57.5, 63.3 (C-6), 71.8, 76.9 (C-3)
16.8, 22.5 (Me), 30.3, 31.3 (C-4), 31.8, 38.1 (C-5), 57.0, 64.5
(C-6), 59.9, 66.9 (C-3a), 73.7, 76.2 (C-3)
25.6 (endo-Me), 25.9 (exo-Me), 30.0 (C-4), 37.4 (C-5), 56.2
(C-3a), 64.9 (C-6), 73.0 (C-3)
Reaction and
level of theory
Starting
compound
Transition
state
Product
5b[d]
5c
2a!TS!3a
B3-LYP/QZVP
MP2/cc-pVTZ
4a!TS!5a
0.00
0.00
127.09
108.64
83.74
72.70
11a
26.6, 34.9 (C-2’), 32.7, 39.4 (C-1’), 33.3, 49.6 (C-3’), 100.3,
109.8 (C-2, C-4, C-6)
B3-LYP/QZVP
MP2/cc-pVTZ
4a!TS!5b
B3-LYP/QZVP
MP2/cc-pVTZ
0.00
0.00
105.18
55.61
ꢀ38.75
ꢀ59.83
[a] Chemical shift (d) values measured in CDCl3 at room temperature;
for the numbering of carbon atoms, see Schemes 1 and 2. [b] Calculated
values given in italics. For all compounds, the NMR spectroscopic chemi-
cal shifts have been calculated at the B3-LYP/QZVP level of theory
except for compound 11a, for which the QZVP basis set has been used
for carbon and oxygen and the TZVPP basis set for all other atoms. All
values have been referenced to TMS, for which the absolute chemical
shift has been calculated as d=182.5 ppm at the B3-LYP/QZVP level of
theory. [c] Measured also in CDCl3 and reported in ref. [1] without as-
signment. [d] The signal assignments of C-4 and C-5, which result from
measurement, might be exchanged. The same is true for the measured
signals of C-3a and C-6.
0.00
0.00
111.99
58.22
ꢀ28.64
ꢀ51.61
compounds, the cut through the potential hypersurface for
the reaction of 2a to form 3a shows that the reaction is en-
dothermic and that compound 3a is at most a metastable
species (Figure 1). Furthermore, the results from the calcula-
Conclusion
To the best of our knowledge, cycloaddition of organic
azides at the double bond of carbonyl compounds is un-
known. This holds true after a thorough reinvestigation of a
report on 4,5-dihydro-1,2,3,4-oxatriazoles claimed to result
from g-azido aldehydes. Our results reveal new insight into
intramolecular 1,3-dipolar cycloaddition reactions of azides.
Experimental Section
Caution: Care must be taken in handling azides, which are explosive. In
particular, neat azides can lead to heavy explosions upon friction, impact,
or heating.
Instrumentation and measurements: FTIR spectra were recorded using a
Bruker IFS 28 FTIR spectrophotometer. IR measurements were made
using solutions in KBr cuvettes. 1H NMR spectra were recorded using a
Varian Unity Inova 400 spectrometer operating at 400 MHz. Using the
same spectrometer, 13C NMR spectroscopic data were achieved at
100 MHz. All measurements were performed at room temperature if not
otherwise mentioned. NMR spectroscopic signals were referenced to
TMS (d=0 ppm) or solvent signals recalculated relative to TMS. The
Figure 1. Energy profiles (MP2/cc-pVTZ) and structures of compounds
3a and 5a and 5b formed from 2a and 4a, respectively, and the corre-
sponding transition states (see Table 1 for details).
Chem. Eur. J. 2011, 17, 5539 – 5543
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5541

S. Firdous, K. Banert, and A. A. Auer
multiplicities of 13C signals were determined with the aid of DEPT135 ex-
periments. The assignment of the signals was confirmed by gCOSY,
gHSQCAD, and gHMBCAD experiments. The elemental analyses were
carried out using a Vario Micro Cube from Elementar. Elemental analy-
ses of explosive azides and highly unstable bromide could not be per-
formed. TLC was conducted using Macherey–Nagel Polygram SIL G/
UV254 polyester sheets. Flash column chromatography was performed
with 32–63 mm silica gel.
Compound 1b: By following a known[9] procedure, 4-hydroxybutyl 4-
methylbenzenesulfonate was prepared and used without further purifica-
tion. 4-Hydroxybutyl 4-methylbenzenesulfonate (2.0 g, 8.18 mmol) was
added over several minutes to a stirred mixture of pyridinium chloro-
chromate (PCC; 2.50 g, 11.6 mmol) in CH2Cl2 (20 mL), under nitrogen at
08C. After 1 h, the mixture was diluted with pentane (10 mL), and the
solvent was decanted off. The black residue was extracted twice with pen-
tane (10 mL). The combined pentane extracts were filtered through a
short plug of silica gel, using pentane as eluant. After removal of the sol-
6H), 4.90 ppm (t, 3J=4.4 Hz, 3H); 13C NMR (CDCl3): d=22.8 (t; CH2),
31.2 (t; CH2), 51.1 (t; CH2), 100.5 ppm (d; CH); IR (CCl4): n˜ =2933, 2864
(CH2), 2095 cmꢀ1 (N3).
Compound 1c: Bromide 12 was prepared from the corresponding alcohol
by following a known procedure with 85% yield and used for the next
step without further purification.[12] In a 500 mL round-bottomed, three-
necked flask with magnetic stirrer and fitted with gas inlet for ozonolysis
and thermometer, the gas outlet was connected with a flask that bore a
saturated solution of potassium iodide. A solution of 12 (1 g, 5.65 mmol)
in CH2Cl2 (250 mL) was cooled to ꢀ788C, and ozone was bubbled
through the solution for approximately 1.5 h at ꢀ788C until a persistent
brown color appeared in the saturated solution of potassium iodide. Ni-
trogen gas was then bubbled through the solution for 30 min, and dimeth-
yl sulfide (3.75 mL, 50 mmol) was added. The reaction mixture was
warmed slowly to room temperature and stirred for 12 h. The solvent
and excess amount of dimethyl sulfide was removed under vacuum at
ꢀ208C under a fume hood to obtain the crude product, which was puri-
fied by flash chromatography on silica gel, eluting with CH2Cl2 to yield
1c as a highly unstable light-yellow liquid (160 mg, 0.89 mmol, 16%)
after the removal of solvent. 1H NMR (CDCl3): d=1.76 (s, 6H), 2.10 (t,
vent, 1b was isolated as
a colorless oil (1.56 g, 6.46 mmol, 79%).
1H NMR (CDCl3): d=1.95 (m, 2H), 2.44 (s, 3H; CH3), 2.55 (m, 2H),
4.05 (t, J=6.0 Hz, 2H; 1’-H), 7.34 (m, 2H; Ar), 7.75 (m, 2H; Ar),
9.70 ppm (brs, 1H; CHO); 13C NMR (CDCl3): d=21.41 (t; CH2), 21.6
(q; CH3), 39.5 (t; CH2), 69.3 (t; CH2), 127.8 (d; CH, Ar), 129.8 (d; CH,
3
J=7.2 Hz, 2H; 3-H), 2.76 (td, J=7.6 Hz, J=1.2 Hz, 2H; 2-H), 9.82 ppm
(t, 3J=1.2 Hz, 1H; 1-H); 13C NMR (CDCl3): d=34.2 (q; CH3), 38.8 (t;
Ar), 132.7 (s; C, Ar), 144.9 (s; C, Ar), 200.4 ppm (d; C=O); IR (CDCl3):
CH2, C-3), 41.5 (t; CH2, C-2), 66.2 (s; C-4), 201.0 ppm (d; C-1). The as-
ꢀ1
signment of signals was made by 13C,1H shift correlation (gHSQCAD
ꢀ
ꢀ
n˜ =2745 (H C=O), 1713 (C=O), 1599 (Ar), 1495 (Ar), 1178 cm (C O).
ꢀ1
Compound 2a: Following a known procedure,[8] compound 1a was pre-
pared from 4-bromo-1-butanol as a colorless liquid with 60% yield with-
out further purification. The azide 2a was synthesized by the reaction of
1a with NaN3 in DMF in 60% yield or analogously from 1b with 56%
yield. Colorless oil. 1H NMR (CDCl3): d=1.88 (quin, 3J=6.8 Hz, 2H),
2.55 (td, 3J=7.2 Hz, 3J=1.2 Hz, 2H), 3.33 (t, 3J=6.4 Hz, 2H), 9.77 ppm
(t, 3J=1.2 Hz, 1H); 13C NMR (CDCl3): d=21.2 (t; C-3), 40.5 (t; C-2),
ꢀ
ꢀ
spectrum); IR (CCl4): n˜ =2719 (C H), 1729 (C=O), 508 cm (C Br).
Compound 4b: According to a known procedure, 14 was synthesized
from hex-5-en-2-one and methylmagnesium iodide as a colorless liquid
with 96% yield and used without further purification.[13] The known[3]
azide 4b was prepared from 14 and HN3 in CHCl3 with significantly im-
proved yield by using 4-methylbenzenesulfonic acid instead of H2SO4. A
solution of 14 (3.0 g, 26.3 mmol) in CHCl3 (10 mL) was added over sever-
al minutes to a stirred solution of HN3 (2.15 g, 50 mmol) and 4-methyl-
benzenesulfonic acid (3.44 g, 20 mmol) in CHCl3 (10 mL) at 08C. The re-
action mixture was slowly warmed to room temperature, stirred for 2 h,
and then diluted with ice water. The chloroform layer was separated,
washed three times with water, and dried over MgSO4. The solvent was
removed at 208C to yield the crude product, which was purified by flash
chromatography (95:5 hexane/ethyl acetate) to give 4b as a light-yellow
oily liquid (2.92 g, 21.0 mmol, 80%). 1H NMR (CDCl3): d=1.27 (s, 6H;
Me), 1.57 (m, 2H; 4-H), 2.12 (m, 2H; 3-H), 5.05 (m, 2H; 1-H), 5.82 ppm
(m, 1H; 2-H); 13C NMR (CDCl3): d=26.0 (q; CH3), 28.5 (t; C-3), 40.5 (t;
C-4), 61.3 (s; C-5), 114.7 (t; C-1), 138.0 ppm (d; C-2); IR (CCl4): n˜ =2975
ꢀ
50.3 (t; C-4), 200.8 ppm (d; CHO); IR (CCl4): n˜ =2775 (C H), 2101 (N3),
1729 cmꢀ1 (C=O).
Compound 11a: Compound 1a is unstable and attempts to distillate at
atmospheric pressure led partially to formation of 11a. However, better
yields of 11a (up to 87%) were achieved if 1a was stored in the freezer
at ꢀ25 to ꢀ308C for 3 weeks. The product 11a was purified by re-con-
densation at 408C under high vacuum (10ꢀ3 mbar). Attempts to re-con-
densate 11a at 1008C led to 1a due to cleavage of the cyclic acetal. Col-
orless oily liquid. 1H NMR (CDCl3): d=1.79–1.84 (m, 6H; H-1’), 1.96–
2.03 (m, 6H; H-2’), 3.43 (t, 3J=6.6 Hz, 6H; H-3’), 4.92 ppm (t, 3J=
5.2 Hz, 3H; 2-H, 4-H, 6-H); 13C NMR (CDCl3): d=26.6 (t; C-2’), 32.7 (t;
(C H), 2096 (N3), 1641 cmꢀ1 (C=C).
ꢀ
C-1’), 33.3 (t; C-3’), 100.3 ppm (d; C-2, C-4, C-6); IR (CCl4): n˜ =2966,
ꢀ1
ꢀ
ꢀ
ꢀ
2833 (CH2), 1077 (HC O CH), 564 cm (CH2 Br); elemental analysis
calcd (%) for C12H21O3Br3: C 31.81, H 4.67; found: C 31.13, H 4.74.
Compound 2b: A solution of KMnO4 (4.74 g, 30 mmol) and MgSO4
(4.0 g) in water (200 mL) was added dropwise to the stirred solution of
4b (2.0 g, 14.4 mmol) in MeOH (15 mL); the temperature was kept be-
tween 0 and 58C. After complete addition, the reaction mixture was
stirred for further 2 h at the same temperature and then filtered to
remove brown precipitates. The filtrate was extracted with chloroform
(5ꢂ15 mL); the layers were washed with NaCl solution and dried over
MgSO4. After removal of solvent, 15 was isolated as a colorless liquid
(2.36 g, 13.64 mmol, 95%). 1H NMR (CDCl3): d=1.25 (s, 6H), 1.47 (m,
2H), 1.57 (m, 2H), 3.20 (brs, 2H), 3.43 (m, 1H), 3.63 ppm (m, 2H);
13C NMR (CDCl3): d=26.0 (q; CH3), 27.6 (t; CH2), 37.3 (t; CH2), 61.3
(s), 66.5 (t; CH2), 72.1 ppm (d; CH).
Compound 11b: Compound 1b was stored in the freezer at ꢀ25 to
ꢀ308C for 3 weeks to give product 11b, which was purified by removing
the starting material at 408C under high vacuum. Heating of 11b at
1008C led to 1b due to cleavage of the cyclic acetal. Yield: 89%; color-
less oil. 1H NMR (CDCl3): d=1.64 (m, 6H), 1.70 (m, 6H), 2.45 (s, 9H),
4.02 (t, J=6.0 Hz, 6H), 4.78 (t, 3J=5.2 Hz, 3H), 7.33 (m, 6H; Ar),
7.77 ppm (m, 6H; Ar); 13C NMR (CDCl3): d=21.6 (q; CH3), 30.0 (t;
CH2), 39.5 (t; CH2), 70.0 (t; CH2), 100.0 (d; CH), 127.8 (d; CH, Ar),
129.8 (d; CH, Ar), 132.9 (s; C, Ar), 144.7 ppm (s; C, Ar); IR (CCl4): n˜ =
ꢀ1
ꢀ
ꢀ ꢀ
2966, 2833 (CH2), 1597 (Ar), 1498 (Ar), 1178 (C O), 942 cm (HC O
CH); elemental analysis calcd (%) for C33H42O12S3: C 54.53, H 5.82, S
13.23; found: C 54.42, H 5.79, S 13.14.
The diol 15 was used for next step without further purification. A solu-
tion of 15 (2.0 g, 11.5 mmol) in 15 mL of dry THF was added slowly over
a period of 1 h to a stirred solution of periodic acid (2.87 g, 15 mmol) in
dry THF (10 mL) under nitrogen at 08C. The reaction mixture was
stirred then for 1 h at room temperature. The solid was filtered off and
extracted with cold THF. The solvent was removed under vacuum at
room temperature to obtain a residue, which was dissolved in ethyl ace-
tate (50 mL) and washed with saturated NaCl solution that contained
15% sodium thiosulfate. The organic layer was dried over MgSO4. The
solvent was removed to give crude product, which was purified by flash
chromatography using CHCl3 as eluant to afford 2b as a light yellow
liquid (1.40 g, 9.91 mmol, 85%). 1H NMR (CDCl3): d=1.29 (s, 6H), 1.81
(t, J=7.6 Hz, 2H), 2.54 (td, J=7.6 Hz, 3J=1.4 Hz, 2H), 9.79 ppm (t, 3J=
Compound 11c: A mixture of 11a (0.88 g, 1.94 mmol) and NaN3 (1.30 g,
20 mmol) in DMF (5 mL) was stirred overnight at 508C. The reaction
mixture was diluted with diethyl ether/hexane (1:1, 25 mL), washed twice
with water and twice with brine, dried over MgSO4, and the solvent was
distilled off under vacuum to yield 11c as colorless liquid (0.56 g,
1.66 mmol, 86%). In an analogous way, 11c was prepared from 11b in
87% yield. The compound 11c was purified by short-path re-condensa-
tion at 258C under high vacuum (10ꢀ3 mbar). No reaction was observed
by repeating the above synthesis at 08C or at room temperature. On stor-
ing 2a at ꢀ25 to ꢀ308C for several weeks, no 11c was formed. Colorless
oily liquid. 1H NMR (CDCl3): d=1.66–1.77 (m, 12H), 3.29 (t, J=6.6 Hz,
5542
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4,5-Dihydro-1,2,3,4-oxatriazoles
FULL PAPER
1.4 Hz, 1H); 13C NMR (CDCl3): d=25.9 (q; CH3), 33.2 (t; CH2), 39.1 (t;
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ꢀ
CH2), 61.2 (s; C), 201.3 ppm (d; CHO); IR (CCl4): n˜ =2719 (C H), 2102
(N3), 1729 cmꢀ1 (C=O).
Computational details: For all computed compounds, geometry optimiza-
tions and the calculation of zero-point energies as well as NMR spectro-
scopic chemical shifts (see Table 2) were carried out at the B3-LYP/
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Acknowledgements
We thank Dr. M. Hagedorn and Dr. N. Ramezanian for assistance with
ozonation and with the manuscript. S.F. is grateful to the DAAD
(Deutscher Akademischer Austauschdienst) for a fellowship. A.A.A. has
been supported by the DFG (Deutsche Forschungsgemeinschaft AU 206/
1-1).
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Received: January 21, 2011
Published online: April 19, 2011
Chem. Eur. J. 2011, 17, 5539 – 5543
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www.chemeurj.org
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