Ozonolysis of

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

The only example involving the 4-5 double bond in a 1-3 dipolar addition is given by the ozonolysis of the optically active 2-aminothiazOle (176) reported by Lardicci et al. (Scheme 112) (17). 

Ozonolysis of 2-styryl-4-methylthiazole followed by oxidation of the intermediate carbonyl compound with peracetic acid yields 4-methyl-2-thiazolecarboxylic acid (30). 

As mentioned previously, aldehydes can be prepared by Stephen s method of reduction of nitriles by stannous chloride (37, 91). Polaro-graphic reduction of thiazolecarboxylic acids and their derivatives gives lower yields of aldehydes (58). Ozonolysis of styrylthiazoles, for example, 2-styryl-4-methylthiazole, followed by catalytic reduction gives aldehyde with 47% yield of crude product (30). 

Ozonolysis has both synthetic and analytical applications m organic chemistry In synthesis ozonolysis of alkenes provides a method for the preparation of aldehydes and ketones... 

FIGURE6 15 Ozonolysis of 2 4 4 trimethyl 2 pentene On cleavage each of the doubly bonded carbons becomes the carbon of a carbonyl (C=0) group... 

Dehydration of 2 2 3 4 4 pentamethyl 3 pentanol gave two alkenes A and B Ozonolysis of the lower boiling alkene A gave formaldehyde (H2C=0) and 2 2 4 4 tetramethyl 3 pentanone Ozonolysis of B gave formaldehyde and 3 3 4 4 tetramethyl 2 pentanone Identify A and B and suggest an explanation for the formation of B in the dehydration reaction... 

Compound A (C7Hi3Br) is a tertiary bromide On treatment with sodium ethoxide in ethanol A IS converted into B (C7H12) Ozonolysis of B gives C as the only product Deduce the struc tures of A and B What is the symbol for the reaction mechanism by which A is converted to B under the reaction conditions ... 

Sabinene and carene are isomeric natural products with the molecular formula CjoHig (a) Ozonolysis of sabinene followed by hydrolysis in the presence of zinc gives compound A What IS the structure of sabinene" What other compound is formed on ozonolysis" (b) Ozonoly SIS of A carene followed by hydrolysis in the presence of zinc gives compound B What is the structure of A carene" ... 

Consider the ozonolysis of tram 4 5 dimethylcyclohexene having the configuration shown... 

Hydrolysis of cinenn I gives an optically active carboxylic acid (+) chrysanthemic acid Ozonolysis of (+) chrysanthemic acid followed by oxidation gives acetone and an optically active dicarboxyhc acid (—) caronic acid (C7H10O4) What is the struc ture of (—) caronic acid" Are the two carboxyl groups cis or trans to each other What does this information tell you about the structure of (+) chrysanthemic acid" ... 

Preparation. The industrial production of malonic acid is much less important than that of the malonates. Malonic acid is usually produced by acid saponification of malonates (9). Further methods which have been recendy investigated are the ozonolysis of cyclopentadiene [542-92-7] (10), the air oxidation of 1,3-propanediol [504-63-2] (11), or the use of microorganisms for converting nitriles into acids (12). 

By-products include ozonides (17). Other peroxidic products including polymeric peroxides and polymeric ozonides can form, depending on reaction conditions, solvent, and olefin used. A variety of cycHc diperoxides (4) have been obtained by ozonolysis of olefins. Both cis- and... 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Ozonolysis of vitamin D2 gave 2,3-dimethylbutanol, showing the side chain to contain the 22 double bond and a C24 methyl group. 

Rhodium catalyst is used to convert linear alpha-olefins to heptanoic and pelargonic acids (see Carboxylic acids, manufacture). These acids can also be made from the ozonolysis of oleic acid, as done by the Henkel Corp. Emery Group, or by steam cracking methyl ricinoleate, a by-product of the manufacture of nylon-11, an Atochem process in France (4). Neoacids are derived from isobutylene and nonene (4) (see Carboxylic acids, trialkylacetic acids). 

Another method that appears to have commercial potential is the ozonolysis of cyclooctene. Ozonolysis is carried out using a short chain carboxyHc acid, preferably propanoic acid, as solvent. The resultant mixture is thermally decomposed in the presence of oxygen at about 100°C to give suberic acid in about 60—78% yield (38—40). Carboxylation of 1,6-hexanediol using nickel carbonyl as catalyst is reported to give suberic acid in 90% yield (41). 

Other methods have been described to produce dodecanedioic acid. Cyclododecene is prepared from cyclododecatriene by partial hydrogenation. Ozonolysis of the cyclododecene followed by oxidation of the intermediate ozonides gives dodecanedioic acid (72). Hydrogenation of riciaoleic acid gives 12-hydroxystearic acid, which upon treatment with caustic at high temperatures, 325—330°C, gives a mixture of undecanedioic and dodecanedioic acids. 

Examples are given of common operations such as absorption of ammonia to make fertihzers and of carbon dioxide to make soda ash. Also of recoveiy of phosphine from offgases of phosphorous plants recoveiy of HE oxidation, halogenation, and hydrogenation of various organics hydration of olefins to alcohols oxo reaction for higher aldehydes and alcohols ozonolysis of oleic acid absorption of carbon monoxide to make sodium formate alkylation of acetic acid with isobutylene to make teti-h ty acetate, absorption of olefins to make various products HCl and HBr plus higher alcohols to make alkyl hahdes and so on. 

For practical use in ozonolysis of compounds it is convenient to recalculate these data to show the time required to produce 0.1 mole of ozone at a specified rate of flow and voltage. This is illustrated by Table II. 

Azelaic acid is made by the ozonolysis of another natural product, oleic acid ... 

From their structures, it appears that the hydrolytic stability of macrocyclic lactones must necessarily be inferior to macrocyclic polyethers. Ease of synthesis of the cyclic esters is therefore one of the aspects which commend them to interest. It is probably for this reason that such lactones have not been made more often by the interesting approach of Kdgel and Schroder . These workers report the ozonolysis of dibenzo-18-crown-6 in a mixture of methanol and dichloromethane at —20°. Reduction of the ozon-ide at —75° using dimethylsulfide followed by warming and addition of acetone led to formation of 6 in 14% yield. The bis-oxalate had mp 164—165° from acetone, very similar to that of the starting crown. The transformation is illustrated below in Eq. (5.9). 

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