Ozonolysi

VI,14. OXIDATION OF UNSATURATED COMPOUNDS WITH OZONISED OXYGEN (OZONOLYSIS)... 

Nickel(O) forms a n-complex with three butadiene molecules at low temperature. This complex rearranges spontaneously at 0 °C to afford a bisallylic system, from which a large number of interesting olefins can be obtained. The scheme given below and the example of the synthesis of the odorous compound muscone (R. Baker, 1972, 1974 A.P. Kozikowski, 1976) indicate the variability of such rearrangements (P. Heimbach, 1970). Nowadays many rather complicated cycloolefins are synthesized on a large scale by such reactions and should be kept in mind as possible starting materials, e.g. after ozonolysis. 

Versatile [3 + 2]-cydoaddition pathways to five-membered carbocydes involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). Palladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n -2-methylene-l,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e. g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopcntane derivatives is accessible. 

Conventional synthetic schemes to produce 1,6-disubstituted products, e.g. reaction of a - with d -synthons, are largely unsuccessful. An exception is the following reaction, which provides a useful alternative when Michael type additions fail, e. g., at angular or other tertiary carbon atoms. In such cases the addition of allylsilanes catalyzed by titanium tetrachloride, the Sakurai reaction, is most appropriate (A. Hosomi, 1977). Isomerization of the double bond with bis(benzonitrile-N)dichloropalladium gives the y-double bond in excellent yield. Subsequent ozonolysis provides a pathway to 1,4-dicarbonyl compounds. Thus 1,6-, 1,5- and 1,4-difunctional compounds are accessible by this reaction. 

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 final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

The oxidative generation of o-aminophenylacetaldehydes can be done by ozonolysis (retrosynthetic path d in Scheme 2.2) but this requires an elec-... 

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). 

The two stage reaction sequence is called ozonolysis and is represented by the gen eral equation... 

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... 

When the objective is analytical the products of ozonolysis are isolated and identi lied thereby allowing the structure of the alkene to be deduced In one such example an alkene having the molecular formula C Hig was obtained from a chemical reaction and was then subjected to ozonolysis giving acetone and 2 2 dimethylpropanal as the products... 

The same reaction that gave 2 4 4 trimethyl 2 pentene also yielded an isomeric alkene This second alkene produced formaldehyde and 4 4 dimethyl 2 pentanone on ozonolysis Identify this alkene... 

Cleavage occurs here on ozonolysis each doubly bonded carbon becomes the carbon of a C=0 unit... 

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... 

The structures of these two CsHie alkenes were deter mined by ozonolysis as de scribed in Section 6 19... 

Alkenes are cleaved to carbonyl compounds by ozonolysis This reaction IS useful both for synthesis (preparation of aldehydes ketones or car boxyhc acids) and analysis When applied to analysis the carbonyl com pounds are isolated and identified allowing the substituents attached to the double bond to be deduced... 

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" ... 

The sex attractant by which the female housefly attracts the male has the molecular formula C23H46 Catalytic hydrogenation yields an alkane of molecular formula C23H4g Ozonolysis yields... 

A certain compound of molecular formula Ci9H3g was isolated from fish oil and from plank ton On hydrogenation it gave 2 6 10 14 tetramethylpentadecane Ozonolysis gave (CH3)2C=0 and a 16 carbon aldehyde What is the structure of the natural product" What is the structure of the aldehyde" ... 

CH3(CH2)ioCH CH3(CH2)4CH and HCCH2CH on ozonolysis What is the constitution of this matenal" ... 

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

Carboxylic acids are produced when alkynes are subjected to ozonolysis... 

Ozonolysis is sometimes used as a tool m structure determination By identifying the carboxylic acids produced we can deduce the structure of the alkyne As with many... 

A certain hydrocarbon had the molecular formula C16H26 and contained two triple bonds Ozonolysis gave CH3(CH2)4C02H and HO2CCH2CH2CO2H as the only products Suggest a reasonable structure for this hydrocarbon ... 

Carbon-carbon triple bonds can be cleaved by ozonolysis The cleavage products are carboxylic acids... 

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