Hydrazinolysis of compounds containing oxazolidine ring

Article abstract of DOI:10.1023/A:1014807426609

We have studied hydrazinolysis of (4S, 5S)-3-benzyl-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidine, (1R, 4S, 5S)-1-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3,3,0]octane, and (1R, 4S,5S)-1-benzyl-4-(4-nitrophenyl)-1-azonia-3,7-dioxabicyclo[3,3,0]octane. We hav

Full text of DOI:10.1023/A:1014807426609

Chemistry of Heterocyclic Compounds, Vol. 38, No. 1, 2002
HYDRAZINOLYSIS OF COMPOUNDS
CONTAINING OXAZOLIDINE RING*
M. Madesclaire1, J. Couquelet1, F. Leal1, V. P. Zaitsev2, and S. Kh. Sharipova2
We have studied hydrazinolysis of (4S,5S)-3-benzyl-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidine,
(1R,4S,5S)-1-(4-nitrophenyl)-1-aza-3,7-dioxabicyclo[3,3,0]octane,
and
(1R,4S,5S)-1-benzyl-4-(4-
nitrophenyl)-1-azonia-3,7-dioxabicyclo[3,3,0]octane. We have shown that neutral compounds are
decomposed with opening of the oxazolidine ring, while quaternary ammonium salts react with
hydrazine in several directions.
Keywords: oxazolidines, perhydrooxazolo[3,4-c]oxazoles, hydrazinolysis.
Reduction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol and (1S,2S)-2-dimethylamino-1-(4-
nitrophenyl)-1,3-propanediol by hydrazine in ethanol in the presence of Raney nickel occurs quantitatively with
formation of a single product [1]. In contrast, reduction of (1R,4S,5S)-1-(4-nitrophenyl)-1-aza-3,7-
dioxabicyclo[3,3,0]octane (1) under the same conditions leads to formation of several compounds, with the
corresponding amino derivative as the major product. We have studied the stability relative to treatment with
hydrazine in ethanol of a number of compounds 1-3 containing oxazolidine ring that we have described
previously in [2,3].
NO2
NO2
NO2
CH CH CH2
CH CH
CH2
OH
CH CH CH2
+
O
N
O
O
N
O
N
O
_
Cl
CH2C6H5
CH2C6H5
3
1
2
Compounds 1-3 were treated with excess hydrazine until decomposition was complete, which simplified
analysis of the reaction mixtures. The course of the reaction was monitored by TLC. Hydrazinolysis was
conducted as follows: each compound was treated with hydrazine in ethanol for 40 h at room temperature and
for 1 h at the boiling point. Then the reaction mixture was evaporated down to half volume on a rotary
_______
* Birthday greetings to our esteemed Mikhail Grigorievich Voronkov! May our collaboration continue for many
more years.
__________________________________________________________________________________________
1
University of Auvergne, Pharmacy Department, 28 Place Henri Dunant, Clermont-Ferrand, France;
2
e-mail: michel.madesclaire@u-clermont1.fr.
vzaitsev@ssu.samara.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 78-80, January,
2002. Original article submitted June 8, 2000.
Samara State University, Samara 443011, Russia; e-mail:
0009-3122/02/3801-0071$27.00©2002 Plenum Publishing Corporation
71

evaporator, and water was added to the residue. The isolated residue (an oil is isolated in the case of compounds
2 and 3, which was then crystallized) was filtered off and dried. The hydrazinolysis products of compounds 2, 3
were identified as hydrochlorides.
As we hypothesized, compounds 1 and 2 react with hydrazine with opening of the oxazolidine ring and
are converted quantitatively to the corresponding amino diols: (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-
propanediol and (1S,2S)-2-benzylamino-1-(4-nitrophenyl)-1,3-propanediol. When compound 3 is treated with
hydrazine, the colorless reaction mixture acquires a yellow-orange color, which suggests that more extensive
conversions are occurring in this case.
For compound 3, we may propose several directions for hydrazinolysis, as shown in the following
scheme:
NO2
cleavage of
oxazolidine rings
CH CH CH2
OH NH OH
1
CH2C6H5
NO2
NO2
alkylation
cleavage of
of hydrazine
oxazolidine rings
2
CH CH CH2
+
CH CH CH2
_
O
N
O
NO2
Cl
CH2C6H5
O
N
O
3
decomposition of
quaternary salt
3
CH CH CH2
OH NH2 OH
NO2
NO2
C
CH
OH
C
O
CH2
CH
OH
CH2
OH
mixture of water-soluble
compounds
+
_
O
N
Cl
CH2C6H5
In practice, we found that compound 3 decomposes preferably in a third direction to form a complex
mixture of mainly water-soluble compounds which were not identified, while the yield of
(1S,2S)-2-benzylamino-1-(4-nitrophenyl)-1,3-propanediol in decomposition via the first direction does not
exceed 20%; this compound proved to be identical to the hydrazinolysis product of compound 2.
We did not detect (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol among the reaction products,
which suggests that in the case of compound 3, the second direction is not realized.
72

EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker AC-400 (400 MHz) spectrometer in DMSO-d6, with
TMS as the internal standard. The spectra were processed using the MESTREC computer program. The specific
rotations were measured on a Jasco DIP-370 polarimeter. The melting points were determined on a Kofler
apparatus. TLC was conducted on aluminum oxide plates (ethanol).
R S S
Hydrazinolysis of (1 ,4 ,5 )-1-(4-Nitrophenyl)-1-aza-3,7-dioxabicyclo[3.3.0]octane (1).
Compound
1 (1.5 g, 6.4 mmol), hydrazine hydrate (2.0 g, 40 mmol), and ethanol (20 ml) were placed in a round-bottomed
flask fitted with a reflux condenser and a magnetic stirrer. The mixture was stirred for 40 h at room temperature
and for 1 h at the boiling point. Then the reaction mixture was evaporated down to half volume on a rotary
evaporator and water (20 ml) was added. The precipitated crystals were filtered off, washed with water, and
dried. Obtained 1.25 g of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol (95% yield); mp 165-166°C
(literature mp: 163-165°C [4]).
S S
Hydrazinolysis of (4 ,5 )-3-Benzyl-4-hydroxymethyl-5-(4-nitrophenyl)oxazolidine (2)
was
conducted as described above, taking compound 2 (2.0 g, 6.4 mmol) and hydrazine hydrate (2 g, 40 mmol).
Obtained 1.88 g of (1S,2S)-2-benzylamino-1-(4-nitrophenyl)-1,3-propanediol (98% yield), which then was
converted to hydrochloride; mp 244-246°C (decomp.), [α]D +55.5° (c 0.52, ethanol). 1H NMR spectrum, δ, ppm,
J (Hz): 7.65-8.24 (4H, q, J = 8.8, Harom); 7.40-7.57 (5H, two m, Harom); 6.75 (1H, br. s, OH); 5.58 (1H, br. s,
OH); 5.07 (1H, br. d, J = 7.5, CHO); 4.30 (2H, s, CH2N); 3.63 and 3.33 (2H, two d, J = 12.8, CH2O); 3.17 (1H,
br. s, CHN). Found, %: C 56.98; H 5.70; N 8.28; Cl 10.48. C16H18N2O4·HCl. Calculated, %: C 56.72; H 5.65;
N 8.27; Cl 10.46.
R S S
Hydrazinolysis of (1 ,4 ,5 )-1-Benzyl-4-(4-nitrophenyl)-1-azonia-3,7-dioxabicyclo[3.3.0]octane
(3) Chloride was conducted as described above, taking compound 3 (2.6 g, 7.1 mmol) and hydrazine hydrate
(2.4 g, 48 mmol). Obtained 0.4 g of (1S,2S)-2-benzylamino-1-(4-nitrophenyl)-1,3-propanediol (18% yield),
which then was converted to hydrochloride; mp 244-246°C (decomp.), [α]D +56° (c 0.52, ethanol). The
1H NMR spectrum is identical to the spectrum of the hydrazinolysis product of compound 2.
REFERENCES
1.
V. M. Potapov, V. M. Dem'yanovich, V. P. Zaitsev, and S. Kh. Sharipova, Zh. Org. Khim., 23, 510
(1987).
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3.
V. P. Zaitsev, P. P. Purygin, and S. Kh. Sharipova, Khim. Geterotsikl. Soedin., 1394 (1990).
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536 (1999).
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Catalog/Handbook of Fine Chemicals, Aldrich Chemical Company, Inc., USA (1996-1997), p. 87.
73