Preparation of Ketones and Aldehydes

Aldehydes and ketones can be prepared by a variety of methods. Because these reactions are needed for many multistep syntheses, Section 21.6 briefly summarizes earlier reactions that synthesize an aldehyde or ketone. 

Aldehydes are prepared from 1° alcohols, e.sters, acid chlorides, and alkynes. 

Thus biacetyl is obtained by treating 2-butanone with isopentyl nitrite and hydrolysing the resultant diketone monoxime (without isolating it) with sulfuric acid.348 The intermediate need also not be isolated when malonic ester is converted into mesoxalic ester by nitrous gases.349 

The nitrosation of substituted ethylbenzenes was carried out by Kovendi and Kirez350 with ethyl or methyl nitrite the resulting benzophenone oxime was hydrolysed by boiling for 3-4 h with 20% hydrochloric acid and the acetophenone produced was extracted with benzene. 

Sachs351 devized a generally applicable method in which activated methylene groups are condensed with iV-dimethyl-p-nitrosoaniline and the resulting Schiff bases are cleaved by dilute mineral acid  

Mehr and his collaboratqrs used this method to convert 4 -substituted tetraphe-nylcyclopentadienes into the corresponding tetraphenylcyclopentadienones 352 

The diene is dissolved in benzene/methanol (3 1 or 3 4), treated with 3 molar equivalents of A,A-dimethyl-/ -nitrosoaniline, and heated to the b.p. Then a few drops of methanolic 10% sodium methoxide solution are added and the mixture is kept for 5-10 min just below the boiling point, next treated with concentrated hydrochloric acid and boiled for 5-10 min. The tetraphenylcyclopentadiene is extracted with benzene. 

We ve already discussed two methods of aldehyde synthesis oxidation of primary alcohols and oxidative cleavage of alkenes. 

Q Primary alcohols can be oxidized to give aldehydes (Section 17.7). The reaction is often carried out using pyridinium chlorochromate (PCC) in dichloro-methane solvent at room temperature. 

3 Alkenes with at least one vinjdic hydrogen undergo oxidative cleavage when treated with ozone, yielding aldehydes (Section 7.9). If the ozonolysis reaction is carried out on a cyclic alkene, a dicarbonyl compound results. 

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by dhsobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at —78 °C (dry-ice temperature) in toluene solution. 

For the most part, methods of ketone synthesis are similar to those for aldehydes. 

Problem 19.3 I How would you prepare pentanal from the following starting materials  

The reaction is often carried out using pyridinium chlorochromate (PCC) in dichloromethane solvent at room temperature  

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to for a more detailed explanation in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes  

For example, the partial reduction of an ester by diisobutylaluminum hydride (DIBAH) is an important laboratory-scale method of aldehyde synthesis. The reaction is normally carried out at -78°C (dry-ice temperature) in toluene solution. 

Organoboranes are used for ketone synthesis under basic conditions. The cyclic ketone 482 is prepared from alkenyl iodode 479. Hydroboration of terminal double bond, followed by carbonylation generates 480, and the cyclic ketone 482 is formed by intramolecular transmetallation of 480 to afford 481 [236], 

Organostannanes, such as aryl-, alkenyl- and alkynylstannanes, are useful for the ketone synthesis via transmetallation of acylpalladium with organostannanes and 

NiBr2 (90%) and NiCl2(Ph3P)2 (92%) can be used as the catalysts for the intramolecular carbonylation of 485 to give 486 [240]. 

The carbonylation of aryl iodide in the presence of terminal alkynes affords acyl alkynes. Bidentate ligands such as DPPF give good results [241]. When PI13P is used, phenylacetylene is mainly converted to diphenylacetylene. The alkynyl ketones 488 are prepared by the reaction of the alkenyl triflate 487 with phenylacetylene and CO [242], 

The acylpalladium is formed by CO insertion as the intermediate of the carbonylation. They can be prepared directly by the oxidative addition of acyl chlorides to Pd(0). Thus ketones can be prepared by the reaction of acyl halides with organozinc reagents and organostannanes. Benzoacetate (490) is obtained by the reaction of benzoyl chloride with the Reformatsky reagent 489 [243], The macrocyclic keto lactone 492 is obtained by intramolecular reaction of the alkenylstannane with acyl chloride in 491 [244]. 

Neither 3-pentanone nor 3-methyl-2-butanone possesses a y-hydrogen therefore, neither is able to undergo McLafferty rearrangement. 

How would you teU the difference between (a) 3-methyl-2-pentanone and 4-methyl-2-pentanone, and (b) 2-ethylcyclohexanone and 3-ethylcyclohexanone, using only mass spectrometry  

Several ways to prepare aldehydes and ketones have already beai desoibed in comieclion with the chemistry of other functional groups (see the Reaction Sunamary Road Map on pp. 780-781). This section reviews the methods that we have studied, pointing out special features and additional examples. Other routes to aldehydes and ketones will be desoibed in lato clupters. 

Laboratory syntheses of aldehydes and ketones use four common methods 

Air is the greenest oxidizing agent. There is currently much research effort aimed at achieving the oxidation of aicohois under mild aerobic conditions. 

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Ozonolysis has both synthetic and analytical applications m organic chemistry In synthesis ozonolysis of alkenes provides a method for the preparation of aldehydes and ketones... 

Preparation of Aldehydes and Ketones from Thio- and Selenoethers... 

IPreparation of Mldehydes Some important methods for the preparation of aldehydes and Ketones and ketones are as follows ... 

Addition of water to alkynes preparation of aldehydes and ketones... 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

Formylation and acetylation of a primary alkyl bromide.2 Detailed directions are available for preparation of disodium tctracarbonylferratesesquidioxanate, Na2Fe(CO)4(dioxanc), 5 (1), and for use of the reagent for preparation of aldehydes and ketones from alkyl bromides. 

Figure 12.1. Preparation of aldehydes and ketones on insoluble supports. M H, metal X leaving group.

A number of useful reactions for the preparation of aldehydes and ketones, such as ozonization of alkenes and hydration of alkynes, have been considered in previous chapters. These and other methods of preparation are summarized in Tables 16-7 and 16-8 at the end of the chapter. Only a few rather general methods that we have not discussed will be taken up here. 

This is a useful route for the preparation of aldehydes and ketones from alkenes, and is covered in this section. Photosensitized oxidative cleavage of alkenes occurs in reasonable yield using p-dimethoxybenzene in the presence of oxygen (equation 31)157. The products are aldehydes or ketones depending upon substrate structure. 

The Swem Oxidation of alcohols avoids the use of toxic metals such as chromium, and can be carried out under very mild conditions. This reaction allows the preparation of aldehydes and ketones from primary and secondary alcohols, resp. Aldehydes do not react further to give carboxylic acids. A drawback is the production of the malodorous side product dimethyl sulphide. 

The oxidising properties of ozone have led to the application of this gas to the bleaching of such substances as starch, flour, oils, and wax, delicate fabrics, etc. It has been used in the production of artificial silk and synthetic camphor. It has also been used to aid the ageing or maturing of wines, spirits, and tobacco. The action of ozone on unsaturated organic compounds provides a very convenient general method for the preparation of aldehydes and ketones, which has already been applied to the manufacture of vanillin for flavouring purposes and heliotropin for perfumery. 

Chromic acid also becomes a selective oxidant for the preparation of aldehydes and ketones when it is supported on an anion exchange resin (Amberlyst A-26 Table 16). The reaction appears to be general and highly tolerant of a wide range of solvents, unlike many resin-based oxidations where the availability of the oxidant is critically dependent upon the nature of the solvent. 

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