Transformations of (-)-α-pinene peroxide ozonolysis products by hydrazines of HCL and H2SO4

Article abstract of DOI:10.1007/s10600-016-1851-9

The reactivities of hydrazines of HCl and H₂SO₄ for (-)-α-pinene peroxide ozonolysis products were studied. It was shown that these reagents were less effective and selective than semicarbazide hydrochloride for transformations into cis-pinonic acid and its esters.

Full text of DOI:10.1007/s10600-016-1851-9

DOI 10.1007/s10600-016-1851-9
Chemistry of Natural Compounds, Vol. 52, No. 6, November, 2016
TRANSFORMATIONS OF (–)-ꢀ-PINENE PEROXIDE OZONOLYSIS
PRODUCTS BY HYDRAZINES OF HCl AND H SO
2
4
Yu. V. Legostaeva, L. R. Garifullina, I. S. Nazarov,
*
A. A. Kravchenko, and G. Yu. Ishmuratov
The reactivities of hydrazines of HCl and H SO for (–)-ꢀ-pinene peroxide ozonolysis products were studied.
2
4
It was shown that these reagents were less effective and selective than semicarbazide hydrochloride for
transformations into cis-pinonic acid and its esters.
Keywords: (–)-ꢀ-pinene, peroxide and non-peroxide ozonolysis products, hydrazine sulfate, hydrazine hydrochloride.
The use of chiral building blocks for targeted synthesis of biologically active compounds is an important and promising
thrust in organic chemistry. ꢀ-Pinene (1), which is isolated from resin and turpentine of various Pinus species, is an available
source of such molecules owing to its native optical activity.
Hydrazine derivatives (2,4-dinitrophenylhydrazine, semicarbazide, and phenylhydrazine, semicarbazide, and
thiosemicarbazide hydrochlorides) are effective reductants for peroxide ozonolysis products of olefins and their derivatives.
Thus, cis-pinonic acid (2) [1] and its methyl [2] and isopropyl [3] esters and disemicarbazone [4] were produced from
ꢀ-pinene using these reagents.
In continuation of research in this area, we studied the reactivities of hydrazine hydrochloride and sulfate toward
peroxide ozonolysis products of 1.
Hydrazine hydrochloride formed intermediate peroxides from 1 that were converted depending on the solvent into
methyl (3) or isopropyl (5) ketoesters or into ketoacid 2, like previously used semicarbazide hydrochloride [1–3]. Hydrazine
hydrochloride was noted to be less reactive and selective than semicarbazide hydrochloride. The peroxides were completely
reduced in alcohols after 1–3 weeks whereas four days were required to convert them into ketoacid 2 in AcOH–CH Cl .
2
2
Furthermore, a mixture of ketoester 3 and ketoacetal 4 was formed if the reaction was carried out in MeOH.
O
O
+
CH(OMe)
CO Me
2
a
d
2
3
, 84%
4, 36%
3, 50%
O
O
i
i
CH(OH)(OPr )
CO Pr
2
b
e
+
+
2, 20%
5
, 56%
6, 13%
5, 73%
1
O
f
c
CO H
2
2
, 84%
2, 88%
a–c: NH NH 4HCl; d–f: NH NH 4H SO ; a, d: O –MeOH, 0°C, 1 week;
2
2
2
2
2
4
3
i
b, e: O –Pr OH, 0°C, 3 week; c, f: O –AcOH–CH Cl , 0°C, 4 days
3
3
2
2
Ufa Institute of Chemistry, RussianAcademy of Sciences, 71 Prosp. Oktyabrya, Ufa, 450054, e-mail: insect@anrb.ru.
Translated from Khimiya Prirodnykh Soedinenii, No. 6, November–December, 2016, pp. 877–879. Original article submitted
March 25, 2016.
©
1020
0009-3130/16/5206-1020 2016 Springer Science+Business Media New York

Changing the acid did not significantly alter the behavior of the hydrazine-based reductants. The main products for
hydrazine sulfate were esters 3 or 5, depending on the solvent, or carboxylic acid 2. Also, ketoacid 2 and ketohemiacetal 6
were obtained via work up of the peroxide ozonolysis products of 1 in i-PrOH.
cis-Pinonic ketoacid 2 was obtained in high yields and is a key compound in the synthesis of the pheromone of the
citrus mealy bug Planococcus citri (Risso), a hazardous citrus pest [4].
The formation of both carbonyl and carboxylic derivatives could be explained by competing transformations of
hydroperoxides 7, i.e., reduction to ketoaldehyde 9, which was isolated as acetals 4 and 6, or dehydration to esters 8, which
could in turn be hydrolyzed to ketoacid 2.
O
+
H O, H
2
+
H
2
CO R
2
-H O
2
O
O
3
OOH
OR
8
9
CH
O
[H]
1
AlkOH
7
CHO
4, 6
i
i
R = Me, Pr , Ac; Alk = Me, Pr
Thus, hydrazine hydrochloride or sulfate transformed peroxide ozonolysis products of 1 into the corresponding ketoacid
or its esters, depending on the solvent. However, these reagents were less reducing and selective than semicarbazide
hydrochloride.
EXPERIMENTAL
General comments were published [2]. Equipment at the Khimiya Center for Collective Use and ꢀ-pinene (Acros
Organics, 97% pure) were used. Elemental analyses of all compounds agreed with those calculated. The ozonator output was
40 mmol O /h.
3
General Method for Ozonolysis of (–)-ꢀ-Pinene (1). An O /O mixture was bubbled through a solution of 1 (1 g,
3
2
7.35 mmol) in MeOH or i-PrOH (25 mL) or a mixture ofAcOH (4.2 mL) and CH Cl (20 mL) at 0°C until 8 mmol of O were
2
2
3
absorbed. The reaction mixture was purged with Ar, stirred, treated at the same temperature with reductant [25.7 mmol;
NH NH 4H SO (3.34 g) or NH NH 4HCl (1.76 g)], and stirred at room temperature until the peroxide disappeared (monitored
2
2
2
4
2
2
using I –starch). The solvent was distilled off. The residue was dissolved in CHCl (150 mL), washed with H O (4 ꢁ 15 mL),
2
3
2
dried over Na SO , and evaporated.
2
4
Work up of Peroxide Ozonolysis Products of 1 by NH NH 4HCl. Ozonolysis in MeOH. Chromatography (SiO ,
2
2
2
hexane, hexane–MTBE, 10:1ꢂ1:1) of the residue (1.6 g) produced ketoester 3 (0.72 g, 50%) and ketoacetal 4 (0.57 g, 36%).
23
Methyl [(1R,3R)-3-Acetyl-2,2-dimethylcyclobutyl]acetate (3). R 0.44, [ꢀ] –24.8° (c 0.73, CH Cl ). The IR and
f
D
2
2
NMR spectra were identical to those published earlier [2].
1-[(1R,3R)-3-(2,2-Dimethoxyethyl)-2,2-dimethylcyclobutyl]ethanone (4). 1.14 g (72%), R 0.40. IR and NMR
f
spectra were identical to those published earlier [5].
Ozonolysis in i-PrOH. Chromatography (SiO , hexane–MTBE, 10:1ꢂ1:1) of the residue (1.3 g) produced
2
ketoisopropyl ester 5 (1.20 g, 73%).
Isopropyl [(1S,3S)-3-Acetyl-2,2-dimethylcyclobutyl]acetate (5). R 0.62. IR and NMR spectra were identical to
f
those published earlier [3].
Ozonolysis in CH Cl –AcOH. Chromatography (SiO , hexane–MTBE, 10:1ꢂ1:1) of the residue (1.30 g) produced
2
2
2
ketoacid 2 (1.19 g, 88%).
20
[(1R,3R)-3-Acetyl-2,2-dimethylcyclobutyl]acetic Acid (2). R 0.21 (hexane–MTBE, 4:1), [ꢀ] –40.0° (CH Cl ,
f
D
2
2
0.8164). IR and NMR spectra were identical to those published earlier [1].
Work up of Peroxide Ozonolysis Products of 1 by NH NH 4H SO . Ozonolysis in MeOH. Chromatography
2
2
2
4
(SiO , hexane, hexane–MTBE, 10:1ꢂ1:1) of the residue (1.40 g) produced ketoester 3 (1.22 g, 84%).
2
1021

Ozonolysis in i-PrOH. Chromatography (SiO , hexane–MTBE, 10:1ꢂ1:1) of the residue (1.70 g) produced
2
ketoisopropyl ester 5 (0.90 g, 56%), ketoacid 2 (0.13 g, 20%), and hemiacetal 6 (0.11 g, 13%).
–1
1-[3-(2-Hydroxy-2-isopropoxyethyl)-2,2-dimethylcyclobutyl]ethanone (6). R 0.37. IR spectrum (KBr, ꢃ, cm ):
f
1
cis
1110 (іΖÑ), 3392 (ÎÍ). Í NMR spectrum (500 MHz, CDCl , ꢄ, ppm, J/Hz): 0.82 (3Í, s, C H ), 1.23 (6Í, d, 2CH ),
3
3
3
trans
1.32 (3Í, s, C
H ), 1.83–2.05 (1Í, m, Í-4), 2.08 (3Í, s, ÑÍ Ñ(Î)), 2.15 (2Í, m, ÑÍ ÑÍ), 2.25–2.35 (1Í, m, Í-1), 2.90
3 3 2
13
(1Í, m, Í-3), 4.02 (1Í, m, ÑÍ(ÑÍ ) ), 4.9 (1Í, m, ÑÍÎÍ), 5.7 (1Í, br.s, ÎÍ). C NMR spectrum (75.47, CDCl , ꢄ, ppm):
3 2
3
22.12 (q, ÑÍ ), 23.23 (q, ÑÍ ), 24.77 (q, 2ÑÍ ), 29.98 (t, Ñ-4), 30.16 (q, ÑÍ Ñ(Î)), 38.09 (t, ÑÍ ), 38.37 (d, Ñ-3), 43.16 (s,
3
3
3
3
2
Ñ-2), 53.79 (d, Ñ-1), 67.54 (d, ÑÍ(CH ) ), 103.45 (d, CÍ(OÍ)OCH(CH ) ), 208.03 (s, Ñ=Î).
3 2
3 2
Ozonolysis in CH Cl –AcOH. Chromatography (SiO , hexane–MTBE, 10:1ꢂ1:1) of the residue (1.35 g) produced
2
2
2
ketoacid 2 (1.13 g, 84%).
ACKNOWLEDGMENT
The work was sponsored by a Grant of the Republic of Bashkortostan to Young Scientists and Young Scientific
Groups (No. 48, Feb. 18, 2016).
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