An IMPROVED PREPARATION OF Ω-Hydroxy ALIPHATIC ACIDS AND THEIR ESTERS

Abstract

Iied~~cti\.e cleavage of the ozonides of aliphatic acids and their esters by sodiuru boroh3-clridc or by hydrogenation produces w-hydroxy aliphatic acids and w-hydrosy aliphatic esters, respectively, in high yields. INTRODUCTIOSw-Difunctional aliphatic compounds have found 1nuc11 ernplo>-~nent in the synthesis of higher aliphatic compounds. Among these, substances having two different terminal functions are the most favored, and probably the most important reagents for chai~l extension are the esters of the w-halogeno acids. These compounds, in various chainlengths, were required for condensation with ~nalonic ester derivatives in the preparation of branched alkanedioic acids (1, 2, 3, 4) in this laboratory. With the exception of those members of the series of very short chain-length, only one w-bromo acid, ll-bromoundecanoic, is easil), available and this substance is best prepared by the peroxiclecatal>,zed addition of hydrogen bromide to 10-unclecenoic acid ( 5 ) . The latter compound is unique among the terminal unsaturated acids in that it is available in quantity ancl this method of preparation cannot be regarded as a neth hod of general applicability. Use of the more common unsaturated acids with non-terminal olefinic linkages as starting materials for the preparation of w-hydroxy acids and w-bromo acids was first explored b>-Adams ( G , 7), who ozonized the esters and isolated w-aldehydo esters. These compounds were then reduced to give the esters of the w-hydroxy acids. A practical difficulty in preparations of this type is the inevitable oxidation of a portion of the aldehydo ester to the half ester of the corresponding dicarboxylic acid. contamination of intermediates with substances in the dicarboxylic acid series is undesirable as such compounds are usually high nlelting and insoluble and therefore difficult to remove. I t is desirable, therefore, to obviate the sensitive aldehyde intermediate by exploitation of the new metal hydride reagents (8) and by selective reductive cleavage of the ozonide-ester prepare the hydrosy ester without isolatioil of the aldehyde. A similar observation on the preparation of primary alcohols by the borohydride cleavage of ozonides appeared while this work mas in progress (9).We have compared the high-pressure 11)-drogenolysis of certain ozonides with their reductive cleavage by sodium borohydricle and the results are su~n~narized in Table I.Yields of hydroxy ester were found to be superior lvllen the borohydride was usecl and the products were also of higher purity as indicated by a narrow boiling range and ease of crystallizatioil of the phenylurethane. When the scale of the preparation was increased, the yield by borohydride cleavage remained the same but the yield b y high-pressure hydrogenation diminished. Sodium borohydride is still an expensive reagent and it may therefore be more ecoilomical to use the hydrogenation method on a large scale.

Reactions of Ozonides: Iii. Ozonolysis of Ethyl 10-Undecenoate in Ethanol

“…50%) (4-7), and alcohols (ca. soy0, by pressure hydrogenolysis) (19) have been reported. In some cases improved yields have been attributed to the use of alcohols for the ozonization solvent (17).…”

“…Decomposition of ozonolysis products under the appropriate conditions has resulted in the preparation of satisfactory yields of carboxylic acids (90-100%) (15, IG), aldehydes (80-90%) (17), and alcohols (7590%) by organohydride reductions (18,19) while moderate yields of amines (40-6070) (11,12), esters (ca. 50%) (4-7), and alcohols (ca.…”

“…In two previous investigations, the implication has been that elevated temperatures increased side reactions (11,17) and direct evidence that the side reactions were significant was obtained from reductive amination experiments where by-products such as aldehydes (12), acids (12), and esters (11) were identified. Since high temperatures were also employed in the ozonolysispressure reduction of ethyl 10-undecenoate (19), reinvestigation of this reaction, using product analysis by g.l.c., demonstrated that the product was a mixture of ethyl 10-hydroxydecanoate and diethyl sebacate. The ratio of the products was dependent upon the activity of the Raney nickel catalyst and also upon the rate of heating of the pressure autoclave.…”

“…By the previo~isly described method, a solution of ethyl 10-undecenoate (20 g) in ethanol (200 ml) was ozonized and hydrogenated using an aged sample of Raney nickel catalyst (19). Hydrogenation was initially carried out a t 2 000 p.s.i.…”

The solid phase synthesis of monoester monoamides and monoester monoalcohols from symmetrical diacid chlorides

“…Ruzicka and Stoll (8) prepared long chain w-hydroxyacids in low yield b y the Baeyer-Villiger oxidation on poorly accessible macrocyclic ketones. Ozonolysis o f naturally occurring olefinic acids followed by reduction with NaBH, gives o-hydroxyaliphatic acids in high yield a s shown by Diaper and Mitchell (9) and Lyncan a n d Adams (10) provided an inexpensive long chain olefinic acid is available. Hydroxymethylbenzoic acids have been ilsually made from unsymmetrical precursors such as p-toluic acid chloride (1 l ) , bromobenzyl bromide (12), or p-cyanotoluene (13).…”