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The behavior of aliphatic (cyclohexanecarboxylic) and aromatic (salicylic and isonicotinic) carboxylic acid hydrazides toward peroxide products of ozonolysis of a terminal alkene, non-1-ene, in protic (methanol) and aprotic solvents (THF, methylene chloride) has been studied. These hydrazides are capable of acting as reducing agents or decomposing intermediate peroxides. For the synthesis of N′-octylidene isoniazid derivative, it is advisable to carry out the reaction in methanol, whereas the use of THF as solvent favors formation of N′-octylidenecyclohexane-1-carbonydrazide. Salicylic acid hydrazide showed a low efficiency; in this case, mixtures of the corresponding hydrazone with octanoic acid or its methyl ester were formed in a low yield.

Optically active cyclobutanediyl- and cyclopropanediylbisalkylidene dihydrazides of isonicotinic and salicylic acids were synthesized when the peroxide products of ozonolysis of (–)-α-pinene and (+)-Δ3-carene were reduced with isonicotinic and salicylic acid hydrazides in methanol, methylene chloride or tetrahydrofuran. Using QSAR models, high antituberculosis activity in combination with low values ​​of acute toxicity and minimal inhibitory concentration was predicted for the obtained compounds.

Treatment of peroxide ozonolysis products of the bicyclic monoterpenes (–)-α-pinene and (+)-3-carene with 4-hydroxybenzohydrazide in methylene chloride or tetrahydrofuran gave the corresponding keto acids, whereas keto esters were formed in methanol.

Reduction of the peroxide ozonolysis products of (–)-α-pinene and (+)-3-carene by capric and benzoic acid hydrazides in CH2Cl2 or THF produced diacylhydrazones either pure or mixed with the corresponding ketoacids. The capric acid diacylhydrazone formed primarily in CH2Cl2; benzoic acid diacylhydrazone, in THF. The only reaction products formed in MeOH were the corresponding ketoesters.

The reaction of hydrazides of alicyclic capric and aromatic benzoic and p-hydroxybenzoic acids with the peroxide product of non-1-ene ozonolysis was studied. Capric acid hydrazide exhibits the strongest reducing properties in aprotic solvents (methylene chloride, THF) and leads to chemoselective and high-yield (~ 80%) formation of the corresponding acylhydrazone. p-Hydroxybenzoic acid hydrazide forms a similar derivative with a yield of 67% only in THF.

Controlled ozonolysis of (S)-(–)-limonene in the presence of Py gave 4-methyl-3-(3-oxobutyl)pent-4-enal or 4-methyl-3-(3-oxobutyl)pent-4-enoic acid depending on the solvent (CH2Cl2 or MeOH). Exhaustive ozonolysis produced 3-acetyl-6-oxoheptanoic acid. Ozonolysis of abietic acid in CH2Cl2 in the presence of Py formed stable epoxytrioxolaneabietic acid; in MeOH–Py, the epoxyketoaldehyde corresponding to cleavage of the C13–C14 bond.

An improved procedure for preparing 4Z-nonen-1-ol, a key intermediate in the synthesis of sex pheromones of cabbage moth and cotton bollworm, from the cyclic butadiene-isoprene dimer (1-methyl-1Z,5Z-cyclooctadiene) was developed. In this procedure, the peroxide product of regioselective partial ozonolysis (0.9 equiv of O3) of the codimer across the trisubstituted double bond is converted in one step to 9-hydroxy-5Z-nonen-2-one with NaBH(OAc)3, the reagent that does not affect the keto groups present in the structure or formed in the process.

A new version has been proposed for the synthesis of analogs of the known herbicides mecoprop (MCPP) and dichlorprop (2,4-DP) by ozonolysis of chloro derivatives of (pent-3-en-2-yloxy)benzene.

Reactions were studied of peroxide ozonolysis products obtained from linear and cyclic alkenes with hydroxylamine prepared in situ from NH2OH·HCl by hydrogen chloride neutralization with sodium acetate. A one-pot reactions sequence was performed: alkene oxidation with ozone → reduction to a carbonyl compound with hydroxylamine → condensation of the carbonyl compound with hydroxylamine providing a possibility of direct transformation of alkenes in keto- and aldoximes excluding the stage of preparation and isolation of the carbonyl compound.

Low-temperature ozonolysis of 2-alkenyl-1,1-dichlorocyclopropanes under different conditions (O3/MeOH–CH2Cl2–NaOH, O3/MeOH or O3/CH2Cl2–AcOH with subsequent treatment with semicarbazide hydrochloride) afforded the corresponding carbonyl and carboxy derivatives at different ratios, depending on the substrate structure and workup procedure. Peroxide products of ozonolysis of 1,1-dichloro-2-ethenylcyclopropane [3-(2,2-dichlorocyclopropyl)-1,2,4-trioxolane and (2,2-dichlorocyclopropyl)(methoxy)methyl hydroperoxide] turned out to be more stable than those derived from 1,1-dichloro-2-ethenyl-2-methylcyclopropane and were isolated in the pure state.

A one-pot procedure has been developed for the synthesis of phenylhydrazones by ozonolysis of olefins in methanol at 0°C and subsequent reduction of peroxide intermediate with excess 1: 2 mixture of phenylhydrazine hydrochloride and sodium acetate.

Tosylhydrazide was shown to be an effective reductant in protic solvents for the peroxide ozonolysis products of ∆3-carene, (–)-α-pinene, and (S)-limonene. Either α,ω-ditosylhydrazones or α,ω-ketotosylhydrazonoacids were formed depending on the nature of the trisubstituted cycloalkene.

Optically active isoniazid derivatives containing a cyclopropane or cyclobutane fragment have been synthesized by ozonolysis of (+)-Δ3-carene and (–)-α-pinene, followed by treatment of the ozonolysis products with isonicotinic acid hydrazide.

Transformations of peroxy products formed by ozonolysis of undecylenic acid derivatives (methyl ester and hydride reduction product, 10-undecen-1-ol) in various protic and aprotic solvents (MeOH, PriOH, tetrahydrofuran, 1: 5 AcOH–CH2Cl2 mixture), occurring under the action of such reductants as hydroxylamine and semicarbazide hydrochlorides, were studied. These reductants exhibit high performance and in some cases high chemoselectivity, which allowed the development of a number of one-pot procedures for the synthesis of acyclic α,ω-bifunctional compounds, the majority of which are widely used in medicine, perfumery, cosmetics, engineering, and chemical industry, e.g., as block synthons in targeted organic synthesis.

Peroxide products of oleic acid ozonolysis treated with semicarbazide and hydroxylamine hydrochlorides in methanol are predominantly converted into methyl nonanoate and dimethyl nonanedioate, in 2-propanol, into isopropyl nonanoate and monoisopropyl ester of nonanedioic acid, and also into nonanenitrile, in tetrahydrofuran and in a mixture of acetic acid with dichloromethane, into nonanoic and nonanedioc acids, and also in nonanal oxime and 9-(hydroxyimino)nonanoic acid.

Research from the last 20 years on the use of ozonolysis of cyclic and acyclic mono- and dienes and aromatic compounds in various steps of the total synthesis of insect pheromones and juvenoids was reviewed.

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.

Hydrochlorides of hydroxylamine and semicarbazide efficiently reduce peroxide products of olefin ozonolysis in a system CH2Cl2-AcOH leading to the formation of carboxylic acids and their derivatives. The application of water as the solvent component favors the increase in the fraction of nitrogen-containing organic compounds (semicarbazones, keto- and aldoximes, nitriles) and reduction in the yield of carboxylic acids.

Treatment with hydroxylamine and semicarbazide hydrochlorides of peroxide products obtained by ozonolysis of olefins in tetrahydrofuran gives mainly carboxylic acids and their derivatives.

In this work, we report the results of lowtempera� ture ozonolysis of benzyl and phenyl allyl ethers for the preparation of methyl benzyland phenoxyace� tates. The esters of arylacetic acids were prepared by two methods: in the methanol-methylene chloride system in the presence of alkali at -65°C or in methanol at -78°C followed by the treatment of intermediate per� oxide products with semicarbazide hydrochloride. The ozonolysis of benzyl and phenyl allyl ethers Ia and Ib in the presence of NaOH was found to lead in high yield and selectivity to esters IIa and IIb, respectively. Byproducts formed in small amounts are the corre� sponding alkoxyacetic aldehydes IIIa and IIIb. At the same time, the treatment of primary ozonation prod� ucts (peroxides) with semicarbazide hydrochloride gives a mixture of esters IIa and IIb and acetals IVa and IVb (Table 1).

Ozonolysis of (1R,3R)-p-menth-4-en-3-ol in methylene chloride or methanol in the presence of pyridine afforded a mixture of equimolar amounts of epimeric 1-[(2R,4S,6S)- and 1-[(2S,4S,6S)-6-hydroxy-4-methyltetrahydro-2H-pyran-2-yl]-2-methylpropan-1-ones. A probable reaction mechanism is discussed.

Hydroxylamine and semicarbazide hydrochlorides were shown to be efficient as reducing agents toward peroxide products of ozonolysis of various olefins with different degrees of substitution. The rate of the transformations aldehyde → aldehyde oxime → nitrile → ester upon treatment of peroxides with hydroxylamine hydrochloride in isopropyl alcohol was lower than in methanol.

Transformations of peroxide products of ozonolysis of various olefins with different degrees of substitution at the double bond by the action of hydroxylamine and semicarbazide hydrochloride in methanol in the presence of water as co-solvent were studied.

The results of ozonolysis of (R)-menth-4-en-3-one in methylene chloride, methanol, or their 1: 1 mixture in the presence of pyridine, triethylamine, or semicarbazide hydrochloride are reported. Probable schemes for the formation of ozonolysis products, including minor ones, are proposed. Nitrogen-containing organic compounds can act as reducing agents toward peroxides or catalyze their rearrangements.

Peroxide products generated by ozonolysis of non-1-ene, 3-carene, stereoisomeric α-pinenes, (−)-limonene, and castor oil were subjected to transformations by the action of semicarbazide and hydrazine-1,2-dicarboxamide in methanol.

Partial ozonolysis of (S)-(−)-limonene in cyclohexane-methanol yields 1-methyl-4-(prop1-en-2-yl)-7,8,9-trioxabicyclo[4.2.1]nonane as a mixture of diastereoisomers at a ratio of 2: 3. Nitrogen-containing organic compounds (semicarbazide and hydroxylamine hydrochlorides) favor cyclization of intermediate ozonolysisreduction products, whereas the reduction with dimethyl sulfide, NaBH4, and NaBH(OAc)3 follows conventional pattern.

Peroxide products of partial ozonolysis of (S)-(-)-limonene (ee 50%) in cyclohexane-methanol at 2–4°C were treated with a solution of HCl in methanol, which led to the formation of a 4: 1 mixture of methyl [(1S)-2,4-dimethoxy-2,4-dimethylcyclohexyl]acetate and [(1S)-2,4-dimethoxy-2,4-dimethylcyclohexyl]acetaldehyde, each being represented by a single pair of diastereoisomers at a ratio of 3: 1.

The review summarizes the main laws of olefin ozonolysis and also further transformation of the peroxide products in “splitting” reactions and at the treatment with oxidants and reducers.

Transformations of peroxide ozonolysis products of cyclic and acyclic natural olefins with different degrees of saturation by hydroxylamine and semicarbazide hydrochlorides were investigated.

Hydroxylamine hydrochloride efficiently reduces peroxide products of olefins ozonolysis into carbonyl compounds. Depending on the substrate character, solvent, and the treatment conditions the arising aldehydes transformed along the route aldehyde→aldoxime→nitrile→ester into individual compounds or their mixtures, or give the corresponding acetals.

Using RHF/3-21G, RHF/6-31G(d, p), MP2/6-31G(d, p), B3LYP/6-31G(fd, p) approximations the structure and 13C NMR spectra of 2-alkylsubstituted cyclohexene-2-ones and 2-alkylacroleins are studied and calculated. In the series of 2-alkylcyclohexene-2-ones the effect of the substituent on a deviation from coplanarity of the C=C-C=O fragment is more expressed in comparison with 2-alkylacroleins. This deviation (5°) is not enough to explain the observed properties of 2-alkylcyclohexene-2-ones due to disturbed conjugation. The particular behavior of (R)-4-mentenone in reactions of 1,4-addition and ozonolysis is explained by a more expressed +I-effect of the alkyl substituent in α-position.

Research from the last 20 years on the use of ozonolysis of cyclic and acyclic mono- and dienes and aromatic compounds in various steps of the total synthesis of insect pheromones and juvenoids was reviewed.

Ozonolysis and reduction of olefinic derivatives of ricinolic acid and L-menthol were studied using hydroxylamine hydrochloride and sodium trisacetoxyborohydride to reduce the peroxide products.

The possibility of functionalizing the alkyl part of ricinolic acid using the Barton reaction was investigated.

A synthesis of the promising optically pure synthon isopropyl-4R-methyl-6-iodohexanoate based on ozonolytic transformation of the product of regiospecific dehydratation of L-(-)-menthol, (R)-p-menth-3-ene, into 2,6R-dimethyl-8-hydroxyoctan-3-one was proposed.

A compound secreted from the mandibular gland of the queen honeybee (Apis mellifera L.) was identified as 9-oxo-2E-decenoic acid (I), a pheromone regulating the behavior and life activity of a bee colony [1]. However, the toxicity and pharmacological properties of compound I have not been studied so far. There are several possible pathways for the synthesis of acid I [1 – 3], most of these schemes being rather cumbersome and requiring expensive initial reactants. We have developed a practical scheme for the synthesis of compound I proceeding from oleic acid (II). The proposed method is based on selective conversions of 9,9-dimethoxynonanoic acid methyl ester (III). Compound III is obtained with a 67% yield via ozonolysis of acid II, followed by reduction and acid methanolysis of the intermediate product. In order to construct the molecule of pheromone I, we use a sequence of regio- and stereoselective conversions of acetal ester III. Sequential alkaline and acid treatments of compound III yield aldehydo acid IV. The carbon chain was elongated by means of cross-coupling of acid IV with a Grignard reagent. This reaction proceeds chemoselectively at the oxo group with the formation of 9-hydroxydecanoic acid (V). In order to form a double 2E-bond, we used -bromination followed by dehydrobromination. To this end, oxy acid V was converted into an acetoxy derivative (VI), then into chloroanhydride, and treated sequentially with bromine and ethanol. The resulting brominated ester VII was first subjected to soft dehydrobromination with calcium carbonate and then to complete alkaline hydrolysis, which led to 9-hydroxy-2E-decenoic acid (VIII). Finally, Acid VIII was oxidized by the Jones reagent to obtain the target acid I with an overall yield of 16% (calculated for the initial compound II).

A practical synthesis of biologically active 10-hydroxy- and 9-oxo-2E-decenoic acids, components of mandibular gland secretion of honeybee (Apis mellifera L.), is developed using ozonolysis-reduction of oleic acid and 1,9-diacetoxynon-1-ene in the key steps.

A new approach was proposed for the synthesis of 9-oxo-2E-decenoic acid, a multifunctional pheromone of queen honeybee (Apis mellifera L.), starting from the available telomer of butadiene and water (2E,7-octadien-1-ol) using in the key steps partial ozonolysis of the corresponding carbonyl compound, selective oxidation of the conjugated aldehyde into a carboxylic acid, and alkylation of acetoacetic ester to introduce the oxo group.

Hydroxylamine and semicarbazide hydrochlorides are found to be effective reducing agents towards peroxide products of ozonolysis of olefins with different degrees of substitution.

The review summarizes the main laws of olefin ozonolysis and also further transformation of the peroxide products in “splitting” reactions and at the treatment with oxidants and reducers.

A procedure was proposed for direct reduction of peroxide products resulting from ozonolysis of 1-methylcycloalkenes to the corresponding hydroxyketones by the action of sodium triacetoxohydridoborate.

The versatile chiral synthon methyl (R)-5,5-dimethoxy-3-methylpentanoate has been prepared for the first time via ozonolytic decyclization of (R)-4-menthenone, which is available from L-(-)-menthol. The optically pure juvenoid (S)-(+)-hydroprene can be prepared from the synthon

A method for the direct reduction of peroxide products of ozonolysis of 1-alkylcycloalkenes (with Δ3-carene and α-pinene as examples) to the corresponding ketols with NaBH(OAc)3 was proposed.