Pyridine from crotonaldehyde

The first synthesis of sorbic acid was from crotonaldehyde [4170-30-3] and malonic acid [141-82-2] in pyridine in 32% yield (2,17,18)- The yield can be improved with the use of malonic acid salts (19). One of the first commercial methods involved the reaction of ketene and crotonaldehyde in the presence of boron trifluoride in ether at 0°C (20,21). A P-lactone (4) forms and then reacts with acid, giving a 70% yield. 

Sorbic acid has been prepared from crotonaldehyde 1 5 or aldol6 and malonic acid in pyridine solution by hydrogen peroxide oxidation of the condensation product of crotonaldehyde and pyruvic acid 7 and by the action of alkali on 3-hydroxy-4-hexenoic acid,8 9 /3,5-disulfo-w-caproic acid,10 and parasorbic acid.1112... 

Helv. Chim. Acta 2, 338 (1919) from 3-acetyl-1,4-dimethyl -1,2,5,6-tetrahydropyridine Prelog, Komzak, Ber. 74, 1705 (1941) from 7-methylnicotinic acid Rabe, Jantzen, Ber. 54, 925 (1921) from fl-ethy (pyridine KLoenigs, Hoffmann, Ber. 58, 194 (1925) from crotonaldehyde and ammonia Tschi-tschibabin, Oparina, Ber. 60, 1877 (1927). 

Add 4 g. of malonic acid to 4 ml. of pyridine, and then add 3 1 ml. of crotonaldehyde. Boil the mixture gently under reflux over an asbestos-covered gauze, using a small Bunsen flame, for 40 minutes and then cool it in ice-water. Meanwhile add 2 ml. of concentrated sulphuric acid carefully with shaking to 4 ml. of water, cool the diluted acid, and add it with shaking to the chilled reaction-mixture. Sorbic acid readily crystallises from the solution. Filter the sorbic acid at the pump, wash it with a small quantity of cold water and then recrystallise it from water (ca, 25 ml.). The colourless crystals, m.p. 132-133°, weigh ro-i-2 g. 

The bicyclic nature of the labile adduct (79) from 3-methyl-pyridine was established by Acheson and Taylor who found that hydrogenation, yielding (80), followed by oxidation gave pyridine-3,4,5-tricarboxylic acid. This conclusion is consistent with Diels and Alder s observations that acid hydrolysis of the labile pyridine adduct gave pyridine and some crotonaldehyde, whereas alkaline hy-... 

Much work in the review period has concerned enantioselective substitution in five-membered heterocyclics. The enantioselective alkylation of some pyrroles by unsaturated 2-acylimidazoles catalysed by the bis(oxazolinyl)pyridine-scandium(in) triflate complex (31) has been reported.39 Compound (33) is formed in 98% yield and 94% ee from the 2-acylimidazole (32) and pyrrole at —40 °C. A series of enantiomer- ically pure aziridin-2-ylmethanols has been tested as catalysts in the alkylation of /V-mclhylpyrrolc and (V-methylindole by ,/l-unsalura(cd aldehydes.40 Enantiomeric excesses of up to 75% were observed for the alkylation of /V-mcthylpyrrole by ( >crotonaldehyde using (2.S ,3.S )-3-mclhylazirin-2-yl(diphenyl)methanol TFA salt as catalyst to form (34). 

Naturally occurring sorbic acid may be extracted as the lactone (parasorbic acid) from the berries of the mountain ash Sorbus aucuparia L. (Fam. Rosaceae). Synthetically, sorbic acid may be prepared by the condensation of crotonaldehyde and ketene in the presence of boron trifluoride by the condensation of crotonaldehyde and malonic acid in pyridine solution or from 1,1,3,5-tetraalkoxyhexane. Fermentation of sorbaldehyde or sorbitol with bacteria in a culture medium has also been used. 

Pyridine was first isolated, like pyrrole, from bone pyrolysates the name is constrncted from the Greek for fire, pyr , and the suffix idine , which was at the time being used for all aromatic bases - phenetidine, toluidine, etc. Pyridine and its simple alkyl derivatives were for a long time produced by isolation from coal tar, in which they occur in quantity. In recent years this source has been displaced by synthetic processes pyridine itself, for example, can be produced on a commercial scale in 60-70% yields by the gas-phase high-temperatnre interaction of crotonaldehyde, formaldehyde, steam, air and ammonia over a silica-alumina catalyst. Processes for the manufacture of alkyl-pyridines involve reaction of acetylenes and nitriles over a cobalt catalyst. 

Tricyclohexylborane (prepared from cyclohexene and borane), crotonaldehyde, and excess pyridine in toluene stirred 8 days at room temp, under Ng 3-cyclo-hexylbutanal. Y 97%. F. e. s. K. Utimoto et al., Tetrah. Let. 1973, 787. 

A soln. of 3-mercaptobutanal in pyridine containing triethylamine stirred 20 min. at room temp, under Ng, a soln. of crotonaldehyde in pyridine added, stirring continued 20 min. at room temp., and refluxed 14 hrs. 5,6-dihydro-2,6-di-methyl-2H-thiopyran-3-aldehyde. Y 94%. F. e., also from phosphonium salts, s. J. M. McIntosh and H. Khalil, Can. J. Chem. 54, 1923 (1976). 

Acetaldehyde once was widely used as raw material for a variety of large-volume chemical products such as acetic acid and butanol. U.S. usage peaked in 1969 at 1.65 billion lb. Today, most of the former uses have been superseded by routes based on C or other chemistry such as methanol carbonylation to acetic acid and butanol from propylene by oxo chemistry. Of the remaining uses, which totaled about 650 million lb in the United States in 1986, acetic acid still is the major consumer at 50 percent. It also is used as a raw material for pyridine and substituted pyridines, peracetic acid, lactic acid, crotonaldehyde, and 1,3-butylenc glycol. 

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