2-cycloheptanone

VI,34. RING ENLARGEMENT WITH DIAZOMETHANE CYCLOHEPTANONE FROM CYCLOHEXANONE... 

For cyclopentanone, cyclohexanone, and cycloheptanone, the K values for addition are 48, 1000, and 8 M , respectively. For aromatic aldehydes, the equilibria are affected by the electronic nature of the aryl substituent. Electron donors disfavor addition by stabilizing the aldehyde whereas electron-accepting substituents have the opposite effect. 

Experimental evidence, obtained in protonation (3,6), acylation (1,4), and alkylation (1,4,7-9) reactions, always indicates a concurrence between electrophilic attack on the nitrogen atom and the -carbon atom in the enamine. Concerning the nucleophilic reactivity of the j3-carbon atom in enamines, Opitz and Griesinger (10) observed, in a study of salt formation, the following series of reactivities of the amine and carbonyl components pyrrolidine and hexamethylene imine s> piperidine > morpholine > cthyl-butylamine cyclopentanone s> cycloheptanone cyclooctanone > cyclohexanone monosubstituted acetaldehyde > disubstituted acetaldehyde. 

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Enamines formed in this way may be distilled or used in situ. The ease of formation of the enamine depends on the structure of the secondary amine as well as the structure of the ketone. Thus pyrrolidine reacts faster than morpholine or piperidine, as expected from a rate-controlling transition state with imonium character. Six-membered ring ketones without a substituents form pyrrolidine enamines even at room temperature in methanol (20), and morpholine enamines are generated in cold acetic acid (21), but a-alkylcyclohexanones, cycloheptanone, and linear ketones react less readily. In such examples acid catalysis with p-toluenesulfonic acid or... 

Thus, the condensation product of cyclohexanone and ethyl cyanoacetate (125) affords the intermediate (126) for the synthesis of cyclobarbital (112) on alkylation with ethyl bromide. The condensation product of cycloheptanone (127) affords the starting... 

A solution of 100 g of sodium bisulfite in 200 ml of water is added, and the stirring is continued for 10 hours with exclusion of air. A thick precipitate separates after a few minutes. The bisulfite compound is collected by suction filtration, washed with ether until colorless, and then decomposed in a flask with a lukewarm solution of 125 g of sodium carbonate in 150 ml of water. The ketone layer is separated, and the aqueous layer is extracted four times with 30-ml portions of ether. The combined organic layers are dried over anhydrous magnesium sulfate, the ether is removed at atmospheric pressure, and the residual oil is fractionated under reduced pressure through a short column. The cycloheptanone, bp 64-65°/ 2 mm, is obtained in about 40% yield. 

This reaction is nicely applied to total synthesis of Claviilarin A" " as shown in Scheme 7.3. The key reactions involve a high enandoselecdve adchdon-eliminadon process" and stereose-lecdve synthesis of cii -2,3-chsubsdmted cycloheptanones." ... 

Cycloheptanone Cyanoacetic acid methyl ester Ethyl bromide Hydrogen chloride... 

Quingestanol acetate Cycloheptanone Heptabarbitol Cyclohexan-1,3-d lone Molindone Cyclohexanone Cyclobutyrol... 

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. 

A1( -octalone, 45, 80 N-nitioso-N-phenylglycine to N-phenylsydnone, 45, 96 Cyclobutanecarboxylic acid, reaction with hydrazoic acid, 47, 28 Cyclobutene, 1,2,3,4-tetrasiethyl-3,-4-dichloro-, 46, 34 reactions of, 46, 36 Cyclobutylamine, 47, 28 Cyclobutyl isocyanide, 46, 77 Cycloheptanone, 45, 31... 

Posner recently reported a very simple and fast way to activate epoxides towards nucleophilic opening by ketone lithium enolate anions by use of BF3 Et20 (1 equiv.) [73]. The application of this procedure to the nucleophilic opening of propene oxide with the lithium enolate of 2-cycloheptanone, obtained by the conjugate addition of trimethylstannyllithium to 2-cycloheptenone, afforded the stan-... 

Addition of enantiomerically pure cnamines derived from (.Y -jmethoxymethyfipyrrolidine (SMP) and ketones (cyclohexanone, cycloheptanone, propiophenone) to AGY-dimethylmethylene-iminium tetrachloroaluminate11,42 give the corresponding Mannich bases in moderate to good yields (56 -79%) and low to moderate enantioselectivities (30-66% ce)12, l3. The (-)-isomer is the major enantiomer in each case. The absolute configuration of the major enantiomer has not been determined. The auxiliary can be recovered. 

Pimelic Acid (Heptanedioic Acid or 1,5-Pentane-dicarboxytlc Acid). HOOC.(CH2)s.COOH mw 160.17 white prisms mp 106° bp 272° at 100mm (subl), and 212° at 10mm d 1.329 g/cc at 15°. Sol in w, ethanol, eth and hot benz. Prepn is by oxidn of cycloheptanone, capric acid or oleic acid treatment of salicylic acid with Na in amyl ale, or by decarboxylating 1,1,5,5-pentanetetracarboxylic acid with heat Pimelic acid has been combined with cis and trans-, 4-cyclohexanediol to give polyesters, and with m-xylene-ce,ol -diamine or poly-methylenediamines to form polyamides. With diperoxides, the acid forms resins. It is also used as the parent compd to form the expls presented below... 

Auf gleiche Weise liefert Benzaldehyd trans-Stilben (85% d.Th.) und Cycloheptanon Bi-cycloheptyliden (95% d.Th.). ji-Carotin ist mit 85% aus Retinal zuganglich. 

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