Dehydration ketones

Benzoxazoles.—Benzoxazole is cleaved by thiophosgene to the isocyanate (546). The chlorobenzoxazolium salt (547) transforms cyanhydrins RCH(OH)CN into the corresponding chloro-compounds RCHCICN " and it dehydrates ketones RCH2COAr to the acetylenes RC=CAr/ ... 

Reformatski reaction Aldehydes and ketones react with a-bromo- fatty acid esters in the presence of zinc powder to give -hydroxy-esters which may be dehydrated to give a-, 0-unsaturated esters. a-Chloroesters will react if copper powder is used in conjunction with the zinc. 

Metallic sodium. This metal is employed for the drying of ethers and of saturated and aromatic hydrocarbons. The bulk of the water should first be removed from the liquid or solution by a preliminary drying with anhydrous calcium chloride or magnesium sulphate. Sodium is most effective in the form of fine wire, which is forced directly into the liquid by means of a sodium press (see under Ether, Section II,47,i) a large surface is thus presented to the liquid. It cannot be used for any compound with which it reacts or which is affected by alkalis or is easily subject to reduction (due to the hydrogen evolved during the dehydration), viz., alcohols, acids, esters, organic halides, ketones, aldehydes, and some amines. 

Pinacol upon dehydration with acid catalysts e.g., by distillation from 6A sulphuric acid or upon refluxing for 3—4 hours with 50 per cent, phosphoric acid or hydrated oxalic acid) is transformed into methyl ter<.-butyr ketone or plnacolone ... 

Dehydration of the intermediate p-alkoxy- or p-hydroxy ketone can also serve to drive the reaction to the right. 

The reaction product is cooled to room temperature, is washed with 10 ml of H2O to the purpose of removing lithium iodide and is then dehydrated over NaiS04. 3.57 g is obtained of dimethoxy-phenylacetone (III), as determined by gas-chromatographic analysis with an inner standard of 4,4 -dimethoxybeniophenone. The yield of ketone (III) relative to the olefin ( ) used as the starting material is of 87.1%. 

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Both o-aminobenzyl aldehydes and ketones rapidly cyclize and undergo dehydration to indoles. The generation of these carbonyl compounds therefore represents a quite reliable route to indoles. The complication is that while there... 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Secondary amines are compounds of the type R2NH They add to aldehydes and ketones to form carbmolammes but their carbmolamme intermediates can dehydrate to a stable product only m the direction that leads to a carbon-carbon double bond... 

Section 20 18 Nitnles are prepared by nucleophilic substitution (8 2) of alkyl halides with cyanide ion by converting aldehydes or ketones to cyanohydrins (Table 20 6) or by dehydration of amides... 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Perchloric acid Acetic acid, acetic anhydride, alcohols, antimony compounds, azo pigments, bismuth and its alloys, methanol, carbonaceous materials, carbon tetrachloride, cellulose, dehydrating agents, diethyl ether, glycols and glycolethers, HCl, HI, hypophosphites, ketones, nitric acid, pyridine, steel, sulfoxides, sulfuric acid... 

Reactions with Aldehydes and Ketones. The base-catalyzed self-addition of acetaldehyde leads to formation of the dimer, acetaldol [107-89-1/, which can be hydrogenated to form 1,3-butanediol [107-88-0] or dehydrated to form crotonaldehyde [4170-30-3]. Crotonaldehyde can also be made directiy by the vapor-phase condensation of acetaldehyde over a catalyst (53). 

Trifluoromethanesulfonic acid is miscible in all proportions with water and is soluble in many polar organic solvents such as dimethylformamide, dimethyl sulfoxide, and acetonitrile. In addition, it is soluble in alcohols, ketones, ethers, and esters, but these generally are not suitably inert solvents. The acid reacts with ethyl ether to give a colorless, Hquid oxonium complex, which on further heating gives the ethyl ester and ethylene. Reaction with ethanol gives the ester, but in addition dehydration and ether formation occurs. 

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

Membranes and Osmosis. Membranes based on PEI can be used for the dehydration of organic solvents such as 2-propanol, methyl ethyl ketone, and toluene (451), and for concentrating seawater (452—454). On exposure to ultrasound waves, aqueous PEI salt solutions and brominated poly(2,6-dimethylphenylene oxide) form stable emulsions from which it is possible to cast membranes in which submicrometer capsules of the salt solution ate embedded (455). The rate of release of the salt solution can be altered by surface—active substances. In membranes, PEI can act as a proton source in the generation of a photocurrent (456). The formation of a PEI coating on ion-exchange membranes modifies the transport properties and results in permanent selectivity of the membrane (457). The electrochemical testing of salts (458) is another possible appHcation of PEI. 

Methyl Isoamyl Ketone. Methyl isoamyl ketone [110-12-3] (5-methyl-2-hexanone) is a colorless Hquid with a mild odor. It is produced by the condensation of acetone and isobutyraldehyde (164) in three steps which proceed via the keto-alcohol dehydration to 5-methyl-3-hexen-2-one, and hydrogenation to 5-methyl-2-hexanone. 

Methyl vinyl ketone can be produced by the reactions of acetone and formaldehyde to form 4-hydroxy-2-butanone, followed by dehydration to the product (267,268). Methyl vinyl ketone can also be produced by the Mannich reaction of acetone, formaldehyde, and diethylamine (269). Preparation via the oxidation of saturated alcohols or ketones such as 2-butanol and methyl ethyl ketone is also known (270), and older patents report the synthesis of methyl vinyl ketone by the hydration of vinylacetylene (271,272). 

In typical processes, the gaseous effluent from the second-stage oxidation is cooled and fed to an absorber to isolate the MAA as a 20—40% aqueous solution. The MAA may then be concentrated by extraction into a suitable organic solvent such as butyl acetate, toluene, or dibutyl ketone. Azeotropic dehydration and solvent recovery, followed by fractional distillation, is used to obtain the pure product. Water, solvent, and low boiling by-products are removed in a first-stage column. The column bottoms are then fed to a second column where MAA is taken overhead. Esterification to MMA or other esters is readily achieved using acid catalysis. 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

Hydroxyall l Hydroperoxyall l Peroxides. There is evidence that hydroxyalkyl hydroperoxyalkyl peroxides (2, X = OH, Y = OOH) exist in equihbrium with their corresponding carbonyl compounds and other a-oxygen-substituted peroxides. For example, reaction with acyl haUdes yields diperoxyesters. Dilute acid hydrolysis yields the corresponding ketone (44). Reduction with phosphines yields di(hydroxyalkyl) peroxides and dehydration results in formation of cycHc diperoxides (4). 

Polymeric OC-Oxygen-Substituted Peroxides. Polymeric peroxides (3) are formed from the following reactions ketone and aldehydes with hydrogen peroxide, ozonization of unsaturated compounds, and dehydration of a-hydroxyalkyl hydroperoxides consequendy, a variety of polymeric peroxides of this type exist. Polymeric peroxides are generally viscous Hquids or amorphous soHds, are difficult to characterize, and are prone to explosive decomp o sition. 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

Pyrrohdinone (2-pyrrohdone, butyrolactam or 2-Pyrol) (27) was first reported in 1889 as a product of the dehydration of 4-aminobutanoic acid (49). The synthesis used for commercial manufacture, ie, condensation of butyrolactone with ammonia at high temperatures, was first described in 1936 (50). Other synthetic routes include carbon monoxide insertion into allylamine (51,52), hydrolytic hydrogenation of succinonitnle (53,54), and hydrogenation of ammoniacal solutions of maleic or succinic acids (55—57). Properties of 2-pyrrohdinone are Hsted in Table 2. 2-Pyrrohdinone is completely miscible with water, lower alcohols, lower ketones, ether, ethyl acetate, chloroform, and benzene. It is soluble to ca 1 wt % in aUphatic hydrocarbons. 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

A three-step process involving the oxidation of acetophenone, hydrogenation of the ketone to a-phenylethanol, and dehydration of the alcohol to styrene was practiced commercially by Union Carbide (59) until the early 1960s. Other technologies considered during the infancy of the styrene industry include side-chain chlorination of ethylbenzene followed by dehydrochlotination or followed by hydrolysis and dehydration. 

Anhydrous stannous chloride, a water-soluble white soHd, is the most economical source of stannous tin and is especially important in redox and plating reactions. Preparation of the anhydrous salt may be by direct reaction of chlorine and molten tin, heating tin in hydrogen chloride gas, or reducing stannic chloride solution with tin metal, followed by dehydration. It is soluble in a number of organic solvents (g/100 g solvent at 23°C) acetone 42.7, ethyl alcohol 54.4, methyl isobutyl carbinol 10.45, isopropyl alcohol 9.61, methyl ethyl ketone 9.43 isoamyl acetate 3.76, diethyl ether 0.49, and mineral spirits 0.03 it is insoluble in petroleum naphtha and xylene (2). 

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