Hydrogen acid catalyzed

Two synthetic bridged nitrogen heterocycles are also prepared on a commercial scale. The pentazocine synthesis consists of a reductive alkylation of a pyridinium ring, a remarkable and puzzling addition to the most hindered position, hydrogenation of an enamine, and acid-catalyzed substitution of a phenol derivative. The synthesis is an application of the reactivity rules discussed in the alkaloid section. The same applies for clidinium bromide. 

These common features suggest that carbocations are key intermediates m alcohol dehydra tions just as they are m the reaction of alcohols with hydrogen halides Figure 5 6 portrays a three step mechanism for the acid catalyzed dehydration of tert butyl alcohol Steps 1 and 2 describe the generation of tert butyl cation by a process similar to that which led to its for matron as an intermediate m the reaction of tert butyl alcohol with hydrogen chloride... 

Although 2 methylpropene undergoes acid catalyzed hydration m dilute sulfuric acid to form tert butyl alcohol (Section 6 10) a different reaction occurs m more concentrated solutions of sulfuric acid Rather than form the expected alkyl hydrogen sulfate (see Sec tion 6 9) 2 methylpropene is converted to a mixture of two isomeric C Hig alkenes... 

We have seen this situation before m the reaction of alcohols with hydrogen halides (8ection 4 11) m the acid catalyzed dehydration of alcohols (8ection 5 12) and m the conversion of alkyl halides to alkenes by the El mechanism (8ection 5 17) As m these other reactions an electronic effect specifically the stabilization of the carbocation intermediate by alkyl substituents is the decisive factor The more stable the carbo cation the faster it is formed... 

DIBK can be produced by the hydrogenation of phorone which, in turn, is produced by the acid-catalyzed aldol condensation of acetone. It is also a by-product in the manufacture of methyl isobutyl ketone. Diisobutyl ketone ( 1.37/kg, October 1994) is produced in the United States by Union Carbide (Institute, West Virginia) and Eastman (Kingsport, Teimessee) (47), and is mainly used as a coating solvent. Catalytic hydrogenation of diisobutyl ketone produces the alcohol 2,6-dimethyl-4-heptanol [108-82-7]. 

Methyl Isopropyl Ketone. Methyl isopropyl ketone [563-80-4] (3-methyl-2-butanone) is a colorless Hquid with a characteristic odor of lower ketones. It can be produced by hydrating isoprene over an acidic catalyst at 200—300°C (150,151) or by acid-catalyzed condensation of methyl ethyl ketone and formaldehyde to 2-methyl-l-buten-3-one, foUowed by hydrogenation to the product (152). Other patented preparations are known (155,156). Methyl isopropyl ketone is used as an intermediate in the production of pharmaceuticals and fragrances (see Perfumes), and as a solvent (157). It is domestically available from Eastman (Longview, Texas) (47). 

Although not commercialized, both Elf Atochem and Rn hm GmbH have pubUshed on development of hydrogen fluoride-catalyzed processes. Norsolor, since acquired by Elf Aquitaine, had been granted an exclusive European Hcense for the propylene-hydrogen fluoride technology of Ashland Oil (99). Rn hm has patented a process for the production of isobutyric acid in 98% yield via the isomerization of isopropyl formate in the presence of carbon monoxide and hydrofluoric acid (100). 

Enantioselective addition of hydrogen cyanide to hydroxypivaldehyde (25), catalyzed by (lf)-oxynittilase, afforded (R)-cyanohydrin (26) in good optical yield. Acid-catalyzed hydrolysis followed by cyclization resulted in (R)-pantolactone in 98% ee and 95% yield after one recrystallization (56). 

The oxidation of cyclohexane to a mixture of cyclohexanol and cyclohexanone, known as KA-od (ketone—alcohol, cyclohexanone—cyclohexanol cmde mixture), is used for most production (1). The earlier technology that used an oxidation catalyst such as cobalt naphthenate at 180—250°C at low conversions (2) has been improved. Cyclohexanol can be obtained through a boric acid-catalyzed cyclohexane oxidation at 140—180°C with up to 10% conversion (3). Unreacted cyclohexane is recycled and the product mixture is separated by vacuum distillation. The hydrogenation of phenol to a mixture of cyclohexanol and cyclohexanone is usually carried out at elevated temperatures and pressure ia either the Hquid (4) or ia the vapor phase (5) catalyzed by nickel. 

Maltol. Otsuka Chemical Co. in Japan has operated several electroorganic processes on a small commercial scale. It has used plate and frame and aimular cells at currents in the range of 4500—6000 A (133). The process for the synthesis of maltol [118-71 -8], a food additive and flavor enhancer, starts from furfural [98-01-1] (see Food additives Flavors and spices). The electrochemical step is the oxidation of a-methylfurfural to give a cycHc acetal. The remaining reaction sequence is acid-catalyzed ring expansion, epoxidation with hydrogen peroxide, and then acid-catalyzed rearrangement to yield maltol, ie ... 

Kinetic Considerations. Extensive kinetic and mechanistic studies have been made on the esterification of carboxyHc acids since Berthelot and Saint-GiHes first studied the esterification of acetic acid (18). Although ester hydrolysis is catalyzed by both hydrogen and hydroxide ions (19,20), a base-catalyzed esterification is not known. A number of mechanisms for acid- and base-catalyzed esterification have been proposed (4). One possible mechanism for the bimolecular acid-catalyzed ester hydrolysis and esterification is shown in equation 2 (6). 

Manufacturing. Almost all the THE in the United States is currendy produced by the acid-catalyzed dehydration of 1,4-butanediol [10-63-4]. Only one plant in the United States still makes THE by the hydrogenation of furfural (29). Du Pont recendy claimed a new low cost process for producing THE from / -butane that they plan to commercialize in 1995 (30—32). The new process transport-bed oxidizes / -butane to cmde maleic anhydride, then follows with a hydrogen reduction of aqueous maleic acid to THE (30). 

Acid-catalyzed hydrogen exchange Halogenation Acylation and alkylation Mercuration Diazo coupling Nitrosation... 

Acid-catalyzed hydrogen exchange is used as a measure of the comparative reactivity of different aromatic rings (see Table 5). These reactions take place on the neutral molecules or, at high acidities, on the cations. At the preferred positions the neutral isoxazole, isothiazole and pyrazole rings are all considerably more reactive than benzene. Although the 4-position of isothiazole is somewhat less reactive than the 4-position in thiophene, a similar situation does not exist with isoxazole-furan ring systems. 

Migration to the developing electron sextet at nitrogen is not restricted to hydrogen. In (79) there is methyl migration with formation of methylamine and acetone in the acid-catalyzed decomposition of (80), phenyl migration leads to aniline and acetaldehyde. 

IR spectra, 5, 201 Pyrazole, 1-methyl-anodic oxidation, 5, 247 hydrogen exchange acid-catalyzed, 5, 239 2-oxide... 

Pyrazolino[2,3-c][l,2,3]triazoles, 5, 702 Pyrazolium hydroxide, l,2-dimethyl-3,5-diphenylanhydro-4-hydroxy-IR spectra, 5, 201 Pyrazolium salts dequatemization, 5, 269 H NMR, 5, 185 hydrogen exchange at ring carbon, 5, 245 mesoionic compounds, 5, 171 nitrodebromination, 5, 237 reactivity, 5, 217 reduction, 5, 68, 243 synthesis, 5, 156 UV spectra, 5, 199 Pyrazolium salts, amino-reactions, 5, 262 Pyrazolium salts, bromo-nucleophilic displacements, 5, 266 Pyrazolium salts, 1,2-dimethyl-deuteration, 5, 175, 245 hydrogen exchange, 5, 71 acid-catalyzed, 5, 239 reactions... 

This method of preparation is suitable for producing primary alkyl lactates but is unsatisfactory for /3-methallyl lactate because the strong mineral acid catalyzes the rearrangement of methallyl alcohol to isobutyraldehyde. Methyl lactate can be made conveniently (80-85% yield) by heating 1 mole of lactic acid condensation polymer with 2.5-5 moles of methanol and a small quantity of sulfuric acid at 100 for 1-4 hours in a heavy-walled bottle, such as is used for catalytic hydrogenation with a platinum catalyst. 

The preparation of neopentyl alcohol from diisobutylene herein described represents an example of acid-catalyzed addition of hydrogen peroxide to a branched olefin, followed by an acid-catalyzed rearrangement of the tertiary hydroperoxide formed. In addition to neopentyl alcohol, there are formed acetone and also small amounts of methanol and methyl neopentyl ketone by an alternative rearrangement of the hydroperoxide. 

A mercurinium ion has both similarities and differences as compared with the intermediates that have been described for other electrophilic additions. The proton that initiates acid-catalyzed addition processes is a hard acid and has no imshared electrons. It can form either a carbocation or a hydrogen-bridged cation. Either species is electron-deficient and highly reactive. 

The hydration reaction has been extensively studied because it is the mechanistic prototype for many reactions at carbonyl centers that involve more complex molecules. For acetaldehyde, the half-life of the exchange reaction is on the order of one minute under neutral conditions but is considerably faster in acidic or basic media. The second-order rate constant for acid-catalyzed hydration of acetaldehyde is on the order of 500 M s . Acid catalysis involves either protonation or hydrogen bonding at the carbonyl oxygen. 

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