Efficient and convenient method for workup of ozonolysis reaction using sodium hydrosulfite

Article abstract of DOI:10.1080/00397911.2010.531876

An efficient and convenient method is reported for reductive workup of the ozon-olysis reaction using sodium hydrosulfite. Comparisons were made between triethylamine and methyl sulfide for their use as a quenching reagent in the ozonolysis of a variety of alkenes. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.531876

1
Synthetic Communications , 42: 843–848, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.531876
EFFICIENT AND CONVENIENT METHOD FOR WORKUP
OF OZONOLYSIS REACTION USING SODIUM
HYDROSULFITE
Vipin Tyagi and Ashok Kumar Gupta
Department of Chemistry, S.S.V. PG College, Ghaziabad,
Uttar Pradesh, India
GRAPHICAL ABSTRACT
Abstract An efficient and convenient method is reported for reductive workup of the ozon-
olysis reaction using sodium hydrosulfite. Comparisons were made between triethylamine
and methyl sulfide for their use as a quenching reagent in the ozonolysis of a variety of
alkenes.
Keywords Alkenes; ozonolysis; sodium hydrosulfite
INTRODUCTION
Ozonolysis is an important reaction of the cleavage of carbon–carbon double
[
1,2]
bonds.
With a reductive and oxidative workup, it can afford a wide variety of
[
3]
products including alcohols, aldehydes, ketones, acids, and amines. For reductive
workup, a substantial number of reducing agents such as zinc–acetic acid, iodine,
dimethyl sulfide, triphenylphosphine, trimetyl phosphite, and triethylamine have
been employed to attack ozonides (or a-alkoxy hydroperoxides) at a peroxide oxy-
[
4–14]
gen atom to give the corresponding carbonyl compounds.
Numerous methods
are available for the workup of ozonolysis reaction, but the problems associated with
common methods are the use of low temperature for ozonolysis and long reaction
times where the yields are mainly dependent on the low reaction temperature. In a
hunt for a new workup of ozonolysis for alkenes, we tried different reagents (i.e.,
Received August 29, 2010.
Address correspondence to Vipin Tyagi, Department of Chemistry, S.S.V. PG College, Hapur,
Ghaziabad, Uttar Pradesh 245101, India. E-mail: vipin.tyagi.in@gmail.com
8
43

844
V. TYAGI AND A. K. GUPTA
diethyl amine, diisopropylamine, sodium sulfide, and sodium hydrosulfite) for
workup. Based on results and reaction time, we found sodium hydrosulfite to be
an excellent reagent for workup of ozonolysis. Although the exact mechanism of
sodium hydrosulfite in ozonolysis workup is not clear now, further mechanistic stu-
dies and under investigation. Probably it works as reducing agent as well as base. To
the best of our knowledge, use of this reagent as reducing agent in alkenes has not
been reported earlier.
To take advantage of the benefit of sodium hydrosulfite in organic synthesis,
treatment of several different ozonides with sodium hydrosulfite was investigated.
We also compare our results with the traditional method involving methyl sulfide
and triethylamine.
In this article, we describe the use of sodium hydrosulfite reagent for easy and
convenient conversion of alkenes to their corresponding products. The reduction
using this reagent is fast, clean, and high-yielding, and the product needs no further
purification by chromatography. The extraction technique is enough to remove the
by-products and get the spectroscopically pure product.
About 1.0 to 1.8 mol. Equation of reagent is needed for the reaction to go to
completion in 60–260 min.
The results of this finding are summarized in Table 1 and Scheme 1.
In conclusion, convenient workup, low cost, mild reaction conditions, fast
reaction rate, and good yield make this method practical and industrially attractive
for most ozonolysis reactions. To avoid the unpleasant smell of the methyl sulfide
treatment, the tedious separation of the triphenylphosphine treatment, and the acidic
condition of the zinc in acetic acid treatment, the sodium hydrosulfite treatment is an
excellent choice for workup of the ozonolysis reaction.
EXPERIMENTAL
All melting points were taken on an Electrothermal 9300 instrument and are
1
13
uncorrected. The H and C NMR spectra were recorded using a Bruker 300-MHz
spectrometer. The chemical shift data are reported as d (ppm) downfield from tetra-
methylsilane, which is used as an internal standard. Infrared (IR) spectra were taken
with a Perkin-Elmer 882 spectrophotomer, and only noteworthy absorptions are
listed. The structure of the isolated reaction products, reaction time, and yields are
1
shown in Table 1 and were confirmed by IR and H NMR comparisons with auth-
entic samples prepared using methyl sulfide.
General Procedure
Ozone in oxygen was bubbled into a flask with an alkene in dichloromethane at
30 C until the solution turned blue. The excess ozone was expelled by nitrogen
ꢁ
ꢀ
flow. One equivalent of sodium hydrosulfite, 2 equivalents of triethylamine, or 10
equivalents of methyl sulfide were added to the solution, which was warmed to
ꢁ
2
5–30 C and stirred for 1 h. The solvent was removed, and the residue was extracted
with petroleum ether and water. The petroleum ether solution was washed with
water, dried, and evaporated to obtain spectroscopically pure product except for
compounds 4 and 10.

WORKUP OF OZONOLYSIS REACTION
845
Table 1. Reaction of ozonide derivatives obtained from alkenes with sodium hydrosulfite or methyl
sulfide or triethylamine
Na
2
S
2
O
4
Me
2
S
3
Et N
Time
Yield
(%)
Time
Yield
(%)
Time
(h)
Yield
(%)
Entry Starting material
Product
(h)
1.5
(h)
48
1
76
83
11
10
2
1.5
69
48
11
11
72
3
4
2
2
84
92
20
40
81
54
4
4
83
80
5
1.5
86
72
54
3
88
6
1.5
57
24
78
3
78
7
33
65
72
62
48
30
(
Continued )

846
V. TYAGI AND A. K. GUPTA
Table 1. Continued
Na
Time
2
S
2
O
4
Me
2
S
3
Et N
Yield
(%)
Time
Yield
(%)
Time
(h)
Yield
(%)
Entry Starting material
Product
(h)
(h)
72
8
32
43
14
48
42
4-Phenyl-1,2,4-trioxolane (2, Ozonide)
ꢀ
1
Colorless oil; yield: 57%; IR (neat) (v, cm ): 3090, 3063, 3037, 2963, 2928,
1
1
1
2
477, 1351, 1331, 1254, 1130, 1104, 1069, 1041, 936, 905; H NMR (CDCl ) d
3
1
3
.69–2.42 (m, 6H), 5.95 (s, 1H), 7.29–7.52 (m, 5H); C NMR (CDCl ) d 15.8,
3
9.9, 33.0, 103.5, 107.7, 125.5, 128.1, 129.1, 137.6.
5-Oxo-5-phenylpentanal (3)
ꢀ
1
Dark brown liquid; yield: 76.5%; IR (neat) (v, cm ): 3058, 2941, 2896, 2829,
1
2
728, 1719 (HC=O), 1675 (PhC=O), 1596, 1442, 1365, 1226, 1177, 999, 966; H
NMR (CDCl ) d 2.05 (m, 2H), 2.57 (m, 2H), 3.03 (t, 2H), 7.38–7.99 (m, 5H), 9.79
3
1
3
(
s, 1H, CHO); C NMR (CDCl ) d 199.1 (PhC=O), 201.7 (HC=O).
3
5-Oxo-5-phenylpentanoic Acid (4)
Ozone in oxygen was bubbled through a solution of 1-phenylcyclopentene (5 g,
ꢁ
0
.1 mol) in 50 ml dichloromethane at ꢀ30 C until a blue color appeared. The
Scheme 1. Ozonolysis of alkenes mediated by sodium hydrosulfite.

WORKUP OF OZONOLYSIS REACTION
847
reaction mixture was then treated with sodium hydrosulfite (6.64 g, 0.11 mol) at ꢀ
ꢁ ꢁ
0 C, and the reaction was stirred at 25–30 C for 60 min. The reaction mixture
3
was extracted twice with 25 ml water. The aqueous layer was acidified with 1 N
hydrochloric acid, and the off-white precipitate that formed was filtered, washed
with water, and dried under vacuum to obtain spectroscopically pure off-white solid.
ꢁ
ꢀ1
Mp ¼ 121–123 C; IR (KBr) (v, cm ): 2400–3500 (br, ꢀOH), 1706 (C=O), 1686
1
(
PhC=O), 1256, 1244; H NMR (CDCl ) d 2.09 (m, 2H), 2.51 (t, 2H), 3.08 (t,
H), 7.25–8.00 (m, 5H); C NMR (CDCl ) d 178.8 (COOH), 199.5 (PhC=O).
3
1
3
2
3
Benzyloxy Acetaldehyde (5)
ꢀ1
Pale yellow oil; yield: 84%; IR (neat) (v, cm ): 3451, 3067, 3032, 2913, 2866,
825, 2247, 1732 (C=O), 1449, 1386, 1246, 1204, 1107, 1025, 891; 1H NMR (CDCl3)
2
d 4.07 (s, 2H), 4.60 (s, 2H), 7.27–7.38 (m, 5H), 9.68 (t, 1H).
3-(Benzyloxy)propanal (6)
ꢀ
1
Colorless oil; IR (neat) (v, cm ): 3488, 3238, 3204, 3078, 3054, 2990, 2944,
1
1
(
707 (C=O); H NMR (CDCl ) d 1.94 (m, 2H), 2.54 (td, 2H), 3.05 (t, 2H), 4.48
3
1
3
s, 2H), 9.77 (t, 1H); C NMR (CDCl ) d 22.5, 40.8, 69.0, 72.5, 127.6, 128.2,
3
1
38.0, 202.2.
(3-Oxocyclohexyl)acetaldehyde (7)
ꢀ
1
1
Light yellow oil; IR (neat) (v, cm ): 2939, 1704 (C=O), 1224, 724; H NMR
1
3
(
CDCl ) d 1.22–2.57 (m, 11H), 9.79 (s, 1H); C NMR (CDCl ) d 24.9, 31.0, 33.1,
3
3
3
4.3, 39.5, 41.0, 47.4, 50.0, 200.6, (HC=O), 210.2 (C=O).
Methyl(3S,4 R)-5-tert-butoxy-4-[(tert-
butoxycarbonyl)amino]-3-formyl Pentanoate (8)
1
Pale yellow liquid; yield: 84%; H NMR (CDCl ) d 1.45–1.79 (m, 15H),
3
2
1
5
.32–2.99 (m, 2H), 3.01–3.49 (m, 1H), 3.69 (s, 3H), 3.86–4.35 (m, 3H), 9.72 (s,
3
1
H); C NMR (CDCl ) d 22.3, 23.7, 26.4, 26.8, 28.0, 29.3, 29.7, 50.6, 50.9, 51.7,
3
6.1, 65.1, 65.4, 66.0, 80.8, 93.8, 172.1, 200.1.
Biphenyl-2,2’-dicarbaldehyde (9)
ꢁ
1
Light brown solid, yield: 52%, mp ¼ 51–52 C; H NMR (CDCl ) d 7.35 (dd,
3
1
3
2
1
H), 7.61 (m, 4H), 8.05 (m, 2H), 9.82 (d, 1H); C NMR (CDCl ) d 128.5, 128.7,
3
31.5, 133.3, 134.5, 141.1, 191.0.
2’-Formylbiphenyl-2-carboxylic Acid (10)
Ozone in oxygen was bubbled through a solution of phenanthrene (5 g,
ꢁ
0
.1 mol) in 50 ml dichloromethane at ꢀ30 C until a blue color appeared. The reac-
ꢁ
tion mixture was then treated with sodium hydrosulfite (8.13 g, 0.17 mol) at ꢀ30 C

848
V. TYAGI AND A. K. GUPTA
ꢁ
and the reaction was stirred at 25–30 C overnight. The reaction mixture was
extracted twice with 50 ml water. The aqueous layer was acidified with 1 N hydro-
ꢁ
chloric acid with vigorous stirring for 2 h at 5–10 C. The off-white precipitate was
formed, filtered, washed with water, and dried under vacuum to obtain spectrosco-
ꢁ
ꢀ1
pically pure cream color solid. Yield: 73%, mp ¼ 115–116 C; IR (KBr) (v, cm ):
1
2
7
1
500–3600 (br, ꢀOH), 1690 (C=O), 1597, 1398, 1285, 726; H NMR (CDCl ) d
3
1
3
.16–8.09 (m, 8H), 9.70 (s, 1H); C NMR (CDCl ) d 128.3, 127.5, 128.0, 130.0,
3
30.6, 131.7, 133.0, 133.6, 139.4, 171.4 (COOH), 191.6 (CHO).
ACKNOWLEDGMENTS
We are grateful to the analytical division of the Indian Institute of Technology,
Delhi, for their analytical and spectral data. Vipin Tyagi is thankful to Ch. Charan
Singh University, Meerut, Uttar Pradesh, India, for providing the necessary research
facilities.
REFERENCES
1. Bailey, P. S. Ozonation in Organic Chemistry; Academic Press: New York, 1978; vols. 1
and 2.
2. Padwa, A. In 1,3-Dipolar Cycloaddition Chemistry; John Wiley & Sons: New York, 1984;
vol. 2, chapter 11.
3. Bailey, P. S. The reactions of ozone with organic compounds. Chem. Rev. 1958, 58, 925.
4. Murray, R. W. The mechanism of ozonolysis. Acc. Chem. Res. 1968, 1, 313.
5. Belew, J. S. In Oxidation; R. L. Augustine (Ed.); Dekker: New York, 1969; vol. 1, pp.
259–335.
6
7
8
9
. Boger, D. L.; Mullican, M. D.; Hellberg, M. R.; Patel, M. Preparation of optically active,
functionalized cis-d-6-1-octalones. J. Org. Chem. 1985, 50, 1904.
. Pappas, J. J.; Keaveney, W. P.; Gancher, E.; Berger, M. A new and convenient method for
converting olefins to aldehydes. Tetrahedron Lett. 1966, 7, 4273.
. Yoshioka, M. Synthetic studies related to b-lactum antibiotics. Pure Appl. Chem. 1987, 59,
1041.
. Lorenz, O.; Parks, C. R. Ozonides from asymmetrical olefins reaction with triphenylpho-
sphine. J. Org. Chem. 1965, 30, 1977.
1
1
1
0. Carles, J.; Fliszar, S. Etude des oxyphosphoranes en tant qu’interm e´ diaires lors de la
r e´ duction de l’ozonide du styr e` ne par les phosphates. Can. J. Chem. 1972, 50, 2552.
1. Knowles, W. S.; Thompson, Q. E. A convenient method for reduction of hydroperoxide
ozonation products. J. Org. Chem. 1960, 25, 1031.
2. Ellam, R. M.; Padbury, J. M. Base-catalyzed dehydration of a-alkoxybenzyl hydroperox-
ide: Application to zwitterions trapping reaction in ozonolysis. J. Chem. Soc., Chem. Com-
mun. 1972, 1086.
1
1
3. Schreiber, S. L.; Claus, R. E.; Reagan, J. Ozonolytic cleavage of cycloalkenes to termin-
ally differentiated products. Tetrahedron Lett. 1982, 23, 3867.
4. Bertozzi, C. R.; Bednarski, M. D. The synthesis of 2-azido c-glycosyl sugars: Ozonolysis.
Tetrahedron Lett. 1992, 33, 3109.

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