Hydroxy, dehydration from unsaturated acids

Notes. (1) Cyclohex-1-en-l-ylacetic acid may be prepared from ethyl l -hydroxy-cyclohexylacetate (Expt 5.170) by dehydration to the unsaturated ester followed by acidic hydrolysis to the unsaturated acid. An alternative method from cyclohexanone has been described.191... 

The lactone (31), obtainable in three steps from cholanic acid, served as the starting point in a different approach. Phosphorus oxychloride-pyridine dehydration of the corresponding hydroxy-methyl ester afforded a complex mixture of unsaturated esters in which the cis and trans non-conjugated esters (32) predominated Hydrolysis of the entire mixture and treatment of the mixture of free acids with iV-bromosuccinimide gave the new buf-20(22)-enolide (33). DDQ dehydrogenation of (33) could be controlled to yield either the desired bufa-... 

The j8-hydroxy esters obtained by Reformatzki syntheses are very readily dehydrated, so that water is often lost on distillation and hydrolysis then dehydration is completed by heating with acetic anhydride, acetyl chloride, potassium hydrogen sulfate, formic acid, or sulfuric acid. Depending on the nature of the substituents present on the /9-carbon atom, the products are oc,P- or /9,y-unsaturated acids or mixtures of both.43 In a few exceptional cases <%,/ - or /9,y-unsaturated acids can be obtained at will from /9-hydroxy acids by choice of a suitable dehydrating agent an example of this is (1-hydroxy-cyclohexyl)acetic acid (1) which, according to Wallach,44 is converted by potassium hydrogen sulfate or phosphorus(v) oxide into (1-cyclohexenyl)-acetic acid (2) but by acetic anhydride into the isomer, cyclohexylideneacetic acid (3) ... 

MJnsaturated acids are rarely formed from -hydroxy acids by means of dehydrating agents, which, instead, afford lactides and anhydrides or, with loss of formic acid, aldehydes. However,, / -unsaturated nitriles can be obtained from a-hydroxy nitriles (cyanohydrins) by means of thionyl chloride45 or phosphorus(v) oxide,46 and are readily hydrolysed to the corresponding <%,/ -unsaturated acids. 

When /8-propiolactone is heated under pressure with anhydrous ammonia, /3-hydroxypropionamide is obtained. A mole of /3-propiolactone (72 g) is heated under pressure with 5.87 moles (100 g) of ammonia for 16 hr at 100 C to obtain a 50 per cent yield of crude /3-hydrox5rpropionamide, which can be purified by vacuum distillation. By a dehydration reaction, the amination of the lactone of a y-hydroxycarboxylic acid yields a stable cyclic amide or lactam, as is the case when y-butyrolactone is converted to a-pyrrolidone. However, owing to the instability of the four-membered ring, a lactam cannot be formed from ammonia and the lactone of a /8-hydroxycarboxylic acid, such as -propiolactone. When hydroxy-propionamide is dehydrated, no lactam is formed. Only unsaturated acid derivatives can be obtained, as shown in the equation below. 

The most important reactions taking place on the hydroxy groups of alcohols are 0-H bond cleavage and C-O bond cleavage. With the O-H bond cleavage, reactions with strong acids proceed, as do oxidations of primary alcohols to aldehydes, secondary alcohols to ketones and reactions with organic acids (formation of esters). In foods the last three reactions are particularly important, and are usually enzymatically catalysed. Other important reactions are dehydration and the opposite reaction, hydration, which yield unsaturated hydrocarbons from alcohols and isomeric alcohols from unsaturated hydrocarbons, respectively. These reactions are particularly important in terpenic alcohols. In oleochemistry, oxidation and esterification reactions are used for the production of various lipid derivatives. 

We recall that an aldol condensation occurs by attack of a carbanion derived from an aldehyde or ketone on the carbonyl carbon atom of a second molecule of an aldehyde or ketone. The product is a (3-hydroxy carbonyl compound, or an a,P-unsaturated carbonyl dehydration product. Aldol-type condensations also occur when the carbanion is derived from carboxylic acid derivatives. 

A terpene yielding isofenchyl alcohol on hydration, which Wallach considers to be one of the fenchenes, was artificially prepared by converting nopinone into a hydroxy ester by means of bromoacetic ester and zinc-dust. The hydroxy ester is dehydrated by potassium bisulphate, and so yields an unsaturated ester, which on saponification yields an acid from which the terpene results by distillation. This fenchene has the following characters —... 

Dehydration of the aldol products of a Refoimatsky reaction does not normally occur under the usual reaction conditions but is often accomplished in a separate step to prepare unsaturated esters. Acid-promoted dehydration of -hydroxy esters can give significant amounts of nonconjugated unsaturated esters by either kinetic or thermodynamic control. Mirrington and cowoikers found that acetates can be prepared directly from Refoimatsky reaction mixtures by addition of acetyl chloride. Base-promoted elimination of the acetates produced conjugated esters in high yield. For the reaction shown in Scheme 14, the thermodynamic ratio of products (32) (33) is 40 60 and four different acid-promoted dehydration procedures gave at best a 68 32 ratio of products. ... 

Of particular synthetic importance are the subsequent transformations of the initially formed adducts (103) and analogs thereof. For example, hydrolysis of (106) provides the 3-hydroxy-a-amino acid ester (107) together with Val-OMe (Scheme 43). On the other hand, dehydration of (108) with thionyl chloride in the presence of 2,6-lutidine furnishes a mixture (4 1) of (109) and (110) hydrolysis of the former led to the unsaturated amino acid (111 Scheme 44). a-Alkenylglycine methyl esters may be also prepared from the silyl derivatives (112 Scheme 45). An alternative route to a-alkenylglycines features the addition of the metallated derivative of (101) to thioketones followed by S-methylation to provide adducts (113), which undergo elimination of methanethiol upon reaction with Raney nickel (Scheme 46). ... 

Malonyl-ACP, formed from acetyl-CoA (shuttled out of mitochondria) and CO2, condenses with an acetyl bound to the Cys—SH to yield acetoacetyl-ACP, with release of CO2. This is followed by reduction to the n-/3-hydroxy derivative, dehydration to the trans-t -unsaturated acyl-ACP, and reduction to butyryl-ACP. NADPH is the electron donor for both reductions. Fatty acid synthesis is regulated at the level of malonyl-CoA formation. 

Water is removed with especial ease from alcohols whose hydroxyl group is in a /9-position to an oxo, alkoxycarbonyl, nitrile, or nitro group. For example, on aldolization of acetaldehyde the acid present in the reaction medium suffices for dehydration of the product to the unsaturated carbonyl compound, i.e., to crotonaldehyde. One hour s boiling with dilute sulfuric acid suffices for preparation of 3-hepten-2-one from 4-hydroxy-2-heptanone 39... 

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