Patent GB-1024483-A (GB)
Title: Process for the production of ª‡, ª‰-unsaturated aldehydes and ketones
Inventor: WITTIG GEORG
IPC: C07C45/51
Filed: 1963-04-05
Abstract: a ,b -Unsaturated aldehydes or ketones are made by a process which comprises reacting an adldehyde or ketone with a Schiff's base in the presence of or after previous addition of a hydroxide, an amide or alcoholate of an alkali or alkaline earth metal, or an alkali or alkaline earth organo metallic compound, and preferably in the absence of water, the reaction product being first dehydrated and then hydrolysed in a known manner, preferably without first being isolated, or vice versa, or simultaneously, said Schiff's base being obtained from the condensation of an aldehyde or ketone having at least one methyl or methylene group adjacent to the carbonyl group, with a primary amine.  The preferred aldehyde or ketone used as starting material has at least one double bond in conjugation with carbonyl group, or further the Schiff's base contains in its aldehyde or ketone grouping a double bond in conjugation to the CN group. Both the aldehydes or Schiff's bases may contain two carbonyl or two C = N groups in the molecule.  Particularly suitable Schiff's bases are formed by acetaldehyde, propionaldehyde, crotonaldehyde, beta-methylcrotonaldehyde and acetone as one reactant, and cyclohexylamine as the other reactant.  Suitable organometallic compounds are, for example, methyl lithium, phenyl lithium, phenyl sodium, alkali metal acetylides and Grignard compounds. Of the numerous other condensing agents listed typical are lithium amide, sodamide, and lithium piperidide.  Suitable solvents for the reaction include ethers, hydrocarbons, both aliphatic and aromatic, liquid ammonia, dimethylformamide, N-methylpyrrolidone and dimethylsulphoxide. A long list of named aldehydes and ketones which may be used as starting materials include formaldehyde, acetaldehyde, acetone, methoxyacetone, citral, vitamin A aldehyde, beta-ionine, glyoxal, maleindialdehyde. In Example 1 cinnamaldehyde is prepared by condensing ethylidinecyclohexylamine with benzaldehyde using lithium di-isopropyl amide in ether, and hydrolysing the intermediate with sulphuric acid.  Example 2 described the condensation of benzophenone with ethylidenecyclohexylamine using methyl lithium, the isolation of N - (3,3 - diphenyl - 3 - hydroxypropylidene) - cyclohexylamine and its subsequent conversion to beta-phenylcinnamaldehyde. Other intermediates prepared in this example include N-(3,3-diphenyl - 3 - hydroxy - 2 include N-(3,3-diphenyl - 3 - hydroxy -2 - methylpropylidine) - cyclohexylamine from benzophenone and propylidene cyclohexylamine, N - (5,5 - diphenyl - 5 - hydroxypentene-(2) - ylidene - (1) - cyclohexylamine from benzophenone and crotylidenecyclohexalamine, N -(3 - phenyl - 3 - hydroxypropylidene) - cyclohexylamine from benzaldehyde and ethylidenecyclohexylamine, N - [5 - (21,61,61 - trimethylcyclohexene - (11) - yl - (11) - 3 - methyl - 3 -hydroxypentene - (4) - ylidene - (1)] - cyclohexylamine from beta - ionone and ethylidenecyclohexylamine and N - (3 - phenyl - 3 - hydroxybutylidene - (1)) - cyclohexylamine from acetophenone and ethylidenecyclohexyl amine.  The condensation of beta-ionone with ethylidenecyclohexylamine followed by hydrolysis and dehydration yields beta-ionylideneacetaldehyde, ethylidenecyclohexylamine condensed with cyclohexanone after hydrolysis and dehydration of the intermediate beta-[11-hydroxycyclohexyl - (11)] - ethylidene - cyclohexylamine gives cyclohexylideneacetaldehyde, and ethylidenecyclohexylamine condensed with acetophone and subsequently hydrolysed and dehydrated gives beta-phenylcrotonaldehyde. Named products include 6-methyl-octatrien - (3,5,7) - one(2), b -ionone, and cyclocitral.