Hydroxy, dehydration lactones from

In general, dehydration means loss of water molecules from chemical substances, irrespective of their structure. Even if all cases where water is bonded in hydrate form are excluded, a number of reactions remain which also include formation of nitriles from amides, lactones from hydroxy acids etc. However, the present treatment will concentrate on the heterogeneous catalytic decomposition of alcohols in the vapour phase, which can be either olefin-forming or ether-forming reactions, and on the related dehydration of ethers to olefins. 

The synthesis of lactones from saturated aldehydes under the conditions of the Koch synthesis as described by Himmele [660] could proceed either via the mechanism of the Koch synthesis with dehydration of the hydroxy... 

A reaction analogous with that of cyclic-anhydride-formation is the formation of lactones from 7-hydroxy acids and from 7-halogen acids. (Cf. page 39.) A related reaction is the dehydration of acids possessing a carbonyl group in the gamma position. 

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

It has been postulated that secophthalideisoquinoline ene lactams and hydroxy lactams are most probably artifacts of isolation resulting from the reaction of enol lactones or keto acids with ammonia during the extraction process. The hydroxy lactams are probably formed initially and then undergo dehydration to give ene lactams (5,8). For this reason, this section covers the hydroxy lactams in addition to the ene lactams. The hydroxy lactams are... 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

Viridifloric /3-lactone, 143, has been identified as one of the pheromone components of a complex mixture of volatiles released by the pheromone glands of the male Idea leuconoe butterfly during courtship <1996BMC341>. A racemic mixture of both diastereoisomers was synthesized in four steps from the dilithio salt of 3-methylbutyric acid 144 alkylation with ethanal, dehydration of the secondary alcohol with phosphorus pentoxide, dihydroxylation of the C-C double bond with osmium tetraoxide, and finally formation of the /3-lactone by cyclization with sulfonyl chloride. By comparison with the sample isolated from I. leuconoe, the absolute configuration was established to be (2V,3V)-2-hydroxy-2-(l-methylethyl)-3-butanolide 143. 

Decarboxylative dehydration of 3-hydroxycarboxylic acids, f/ireo-S-Hydroxy-carboxylic acids (1) undergo lactones derived from 1. ... 

The equilibrium between a hydroxy acid and its lactone is catalyzed by hydrogen ion. This equilibrium favors lactone formation from y- and S-hydroxy acids removal of the water fornied completes the reaction. /S-Lactones are not obtained directly by this method. Under forced conditions y-lactones are formed from certain /S-hydroxy acids, presumably by dehydration of the latter to olefinic acids followed by lactonization according to method 324. Direct lactonization of hydroxy acids having the hydroxyl group in the epsilon or a more remote position in the chain is difficult. Competing interesterification reactions occur which lead to dimers and polyesters.. Under certain conditions, however, e-caprolactone has been obtained in 63% yield. ... 

Further degradation of [n, R = H and R = CH3] has been achieved as follows. Oxidation of [ii, R = H] with osmium tetroxide afforded 6-y-hydroxy-13-(a /hdihydroxyethyl)-octahydromethyhnorphenol [iv, R = H] which was converted to 6-y-hydroxy-13-aldehydooctahydromethylmorphenol [v, R = H], which resisted all attempts at direct oxidation to the acid. However the oxime [vi, R = H] was dehydrated to 6-y -acetoxy-13 - cyano octahydromethylmorphenol [vii, R = Ac] hydrolysis of which afforded 6-y-hydroxy-13-carboxyoctahydromethylmorphenol [vni, R = H]. This sequence of reactions was repeated with [ii, R = CH3] giving [iv, R = CHS]-[vi, R — CH3] and with 6-a-hydroxy- and 6-a-methoxy- 13-vinyloctahydro-methylmorphenol obtained from a-tetrahydrocodeimethine. [vin, R = H] could not be lactonized. 

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-... 

Scheme 8 Alcohol (94), prepared from (72, was converted to hydroxy hemiacetal (95) upon treatment with potassium carbonate in aqueous isopropanol. Selective oxidation and acetylation yielded ester (96), whose conversion to lactone (97) was achieved without dificulty. Dehydration of (97), followed by cuprate addition, provided (98), whose conversion to phytuberin has already been accomplished.

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. 

Another aspect of the 8-lactone chemistry is the interconversion between 8-lac-tone and 5-hydroxy fatty acid. Under basic aqueous conditions, the equilibrium favors the formation of the 5-hydroxy fatty acids. In contrast, catalytic amounts of acid will cause rapid cyclization/dehydration of the 5-hydroxy fatty acid into the 8-lactone. By utilizing the equilibrium between these two species, 5-hydroxy fatty acids were synthesized directly from meadowfoam oil (Scheme 13). 

Trunk wood of Mezilaurus synandra one of the species of Mezilaurus belonging to the same subtribe as Clinostemon, was shown to contain a similar y-lactone, (2/ ,3, 4S)-2-dodec-cu-enyl-3-hydroxy-4-methylbutanolide (41) (mp 72-76°C, [a]o -7.5 ) (115). The butenolide (42) from the same source is considered to be an artificial dehydration product of the 3-hydroxy-lactone (41). All of the above aliphatic y-lactones were isolated from Lauraceae 2-hy-droxy-4-(heptadec-8 -enyl)butanolide (43) obtained as an oil from the bark of Garcinia mannii (Guttiferae) is the only compound of this type found in other families (53). 

Raw or gently pasteurised milk (e.g. for 10 seconds at 73 °C) has a fine characteristic odour and sweet taste. Typical components present in low concentrations are dimethylsulfide, biacetyl, 2-methylbutan-l-ol, (Z)-hept-4-enal and ( )-non-2-enal. Milk pasteurised at higher temperatures and Ultra High Temperature (UHT) milk present the so-called cooked flavour, the appearance of which is the first measurable manifestation of the chemical changes that occur in heated milk. The substances responsible for the cooked off-flavour are sulfane and other sulfur compounds. Of particular importance are dimethylsulfide, dimethyldisulfide and dimethyltrisullide that are produced from proteins contained in the membranes of fat particles and from thiamine. Also relevant are alkane-2-ones (methylketones) generated by thermal decarboxylation of P-oxocarboxylic acids (mainly hexane-2-one, heptane-2-one and nonane-2-one), y-lactones and 5-lactones produced by dehydration of y- and 5-hydroxycarboxylic acids (mainly 8-decalactone and y- and 8-dodecalactones). Important carbonyl compounds include biacetyl, hexanal, 3-methylbutanal, (Z)-hept-4-enal and ( )-non-2-enal. In the more intensive thermal treatment of milk (sterilisation), products of the Maillard reaction play a role, such as maltol and isomaltol, 5-hydroxymethylfuran-2-carbaldehyde, 4-hydroxy-2,5-dimethyl-2 f-furan-3-one (furaneol) and 2,5-dimethylpyrazine. 

---