Hydrogenation to Aldehydes

Maki and Yokoyama have recently developed an effective catalyst system consisting of Zr02 and a modifier, such as chromium ion, for vapor-phase hydrogenation of both aliphatic and aromatic carboxylic acids and esters to the corresponding aldehydes.25-27 The metal ions used as modifiers markedly improved the activity and life of Zr02 catalyst. As an example, benzoic acid was hydrogenated to benzaldehyde in 

TABLE 10.3 Vapor-Phase Hydrogenation of Carboxylic Acids and Esters to Aldehydes over Modified Zr02 Catalyst0  

Carboxylic Acid or Ester Conversion (%) Selectivity for Aldehyde (%) 

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Ozone converts nitro compounds, where R is alkyl or hydrogen, to aldehydes and ketones... 

Acid chloride hydrogenation to aldehydes is an important synthetic reaction conveniently carried out using some improved procedures. 

In the Rosenmund reaction (Eq. 5-84), acid chlorides are hydrogenated to aldehydes. The catalyst is a supported palladium catalyst (5 % Pd/BaS04) poisoned by sulfur compounds such as quinoline, tiourea, or thiophene to prevent further reduction of the aldehyde. 

IR absorption at 2050-2150 cm followed by hydrogenation to aldehydes and then decarbonylation with hydrocarbon formation (Scheme 7.46). 

Rare earth oxides have been studied to a lesser extent than alkaline earth oxides. However, they show characteristic selectivity in the dehydration of alcohols. Secondary alcohols form 1-olefins, whereas the same reaction over an acid catalyst produces the thermodynamically more stable 2-olefin (312). An example of an industrially important rare earth oxide catalyst is Zr02. It has several applications, including the reduction of aromatic carboxylic acids with hydrogen to aldehydes (314), the dehydration of 1-cyclohexyl ethanol to vinyl cyclohexane (315), and the production of diisobutyl ketone from isobutyraldehyde (316). The extensive use of Zr02 is mainly due to its resistance to poisoning by H2O and CO2, and its inherent catalytic activity is a result of its bifunctional acid-base properties. It contains both weakly acidic and basic sites, neither of which is susceptible to poisoning. The acid-base functionality of Zr02 is displayed in the reaction of alkylamine to nitrile (278) (Fig. 33). To form nitriles from both secondary and tertiary amines, both acid and base sites are required. 

The acyl cobalt carbonyls are very probably then hydrogenated to aldehydes and cobalt hydrocarbonyl, in analogy to the described mechanism for the olefins. As Yokokawa, et al. [298] found, the yield depends strongly on the reaction temperature. At higher temperatures (see table 23), isomerization of the epoxides to the corresponding ketones and aldehydes frequently occurs first. Further reaction gives a large number of polymeric products. 

It is a curious whim of nature that the same coenzyme which in the yeast makes alcohol by attaching hydrogen to aldehyde also occurs in the liver to remove from alcohol the same hydrogen, so that the alcohol becomes aldehyde again, which is then oxidized further. 

By (he direct addition of hydrogen cyanide to aldehydes and ketones, giving cyanhydrins ... 

The Pd-catalyzed hydrogenoiysis of acyl chlorides with hydrogen to give aldehydes is called the Rosenmund reduction. Rosenmund reduction catalyzed by supported Pd is explained by the formation of an acylpalladium complex and its hydrogenolysis[744]. Aldehydes can be obtained using other hydrides. For example, the Pd-catalyzed reaction of acyl halides with tin hydride gives aldehydes[745]. This is the tin Form of Rosenmund reduction. Aldehydes are i ormed by the reaction of the thio esters 873 with hydrosilanes[746,747]. 

The reduction of acyl halides with hydrogen to form aldehydes using Pd catalyst is well known as the Rosenmund reduction[756]. Some acyl chlorides give decarbonyiation products rather than aldehydes under Rosenmund conditions. The diene 890 was obtained by decarbonyiation in an attempted Rosenmund reduction of acetyloleanolic acid chloride (889)[757], Rosenmund reduction of sterically hindered acyl chlorides such as diphenyl- and tnpheny-lacetyl chloride (891) gives the decarbonylated products 892[758],... 

The slow oxidation of primary alcohols, particularly MeOH, is utilized for the oxidation of allylic or secondary alcohols with allyl methyl carbonate without forming carbonates of the alcohols to be oxidized. Allyl methyl carbonate (564) forms 7r-allylpalladium methoxide, then exchange of the methoxide with a secondary or allylic alcohol 563 present in the reaction medium takes place to form the 7r-allylpalladium alkoxide 565, which undergoes elimination of j3-hydrogen to give the ketone or aldehyde 566. The lactol 567 was oxidized selectively with diallyl carbonate to the lactone 568 without attacking the secondary alcohol in the synthesis of echinosporin[360]. 

The most obvious way to reduce an aldehyde or a ketone to an alcohol is by hydro genation of the carbon-oxygen double bond Like the hydrogenation of alkenes the reac tion IS exothermic but exceedingly slow m the absence of a catalyst Finely divided metals such as platinum palladium nickel and ruthenium are effective catalysts for the hydrogenation of aldehydes and ketones Aldehydes yield primary alcohols... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitnles arises both from the reactivity of the C=N bond, and from the abiHty of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxyHc acids and esters, aldehydes, ketones, large-ring cycHc ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy pubHshed (10). 

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). 

Reduction Reactions. Aldehydes can be hydrogenated to the corresponding alcohol using a heterogeneous catalyst, for example... 

Often the aldehyde is hydrogenated to the corresponding alcohol. In general, addition of carbon monoxide to a substrate is referred to as carbonylation, but when the substrate is an olefin it is also known as hydroformylation. The eady work on the 0x0 synthesis was done with cobalt hydrocarbonyl complexes, but in 1976 a low pressure rhodium-cataly2ed process was commerciali2ed that gave greater selectivity to linear aldehydes and fewer coproducts. 

In the early 1920s Badische Arulin- und Soda-Fabrik aimounced the specific catalytic conversion of carbon monoxide and hydrogen at 20—30 MPa (200—300 atm) and 300—400°C to methanol (12,13), a process subsequendy widely industrialized. At the same time Fischer and Tropsch aimounced the Synth in e process (14,15), in which an iron catalyst effects the reaction of carbon monoxide and hydrogen to produce a mixture of alcohols, aldehydes (qv), ketones (qv), and fatty acids at atmospheric pressure. 

Ru(1PP)2(00)2, at 2000 ppm mthenium and 1-hexene as substrate, gives only an 86% conversion and a 2.4 1 linear-to-branched aldehyde isomer ratio. At higher temperatures reduced conversions occur. High hydrogen partial pressures increase the reaction rate, but at the expense of increased hydrogenation to hexane. Excess triphenylphosphine improves the selectivity to linear aldehyde, but at the expense of a drastic decrease in rate. 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Fig. 6. Campholenic aldehyde (81) reacts with 2-butanone to produce ketones that are hydrogenated to alcohols having the odors indicated.

When the a,P-unsaturated ketone is hydrogenated to the alcohol, a product with an intense sandalwood odor is produced (162). Many other examples of useful products have been made by condensation of campholenic aldehyde with ketones such as cyclopentanone and cyclohexanone. 

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