Dehydration of Aldehydes

Opnns, A D., Geuze, H J, and Slot, J W (1994) Cryosubstitution dehydration of aldehyde-fixed tissue, a favourable approach to quantitative immunocytochemistry J Histochem Cytochem 42,497—503... 

RCH = CHNOj, in alcoholic solution at 0° forms nitroamines, e.g., l-nitro-2-aminopropane (55%) and 2-nitro-3 aminobutane (60%). The reaction is general and is applied to numerous nitro olefins readily obtained by the dehydration of aldehyde-nitroparaffin condensation products. ... 

In the dehydration of aldehydes to form nitriles, Ley and colleagues used a polymer-supported hydrazine (Scheme 6.3). The immobilized hydrazine was reacted with aldehydes to give a hydrazone. Subsequent oxidation with mCPBA (meta-chloroperoxybenzoic acid) rendered the corresponding N-oxide, which spontaneously eliminated to form the desired nitrile [10]. Polyvinylpyridine was used as a scavenger for excess mCPBA. 

A summary of some typical processes for which borosilicates are of interest was provided by Holderich in 1986 (56). Advantages in their use were reported for double bond migrations in carbonyl containing compounds (aldehyde - ketone rearrangement), for the dehydration of aldehydes, for aldol... 

These systems are reported as cyclopentaoxazolidines and can be obtained by conventional azeotropic dehydration of aldehydes with amino alcohols <85TL5303> for example, (S)-5-Hydroxymethyl-2-pyrrolidinone (236) was condensed with benzaldehyde to obtain the corresponding chiral 5-oxo-2-phenylperhydropyrrolo[l,2-c]oxazole (237) in excellent yield <86JOC3140>. Similar treatment of enantiomerically pure amino ketone (238) with paraformaldehyde or formalin under a variety of Mannich conditions yielded (239) <84ja5360>. These reactions are shown in Scheme 41. 

The Polymerization of Aldehyde is readily effected. When aldehyde is warmed with a strong solution of an alkali, the solution becomes yellow in color and a resin-like substance precipitates. This is called aldehyde-resin. Its chemical composition is not known. It is probably formed as the result of polymerization and dehydration of aldehyde. It will be remembered that formaldehyde is not converted into a resin in this way. The reaction is, however, characteristic of other aldehydes. 

Catalysts used for dehydration of aldehyde are phosphoric acid or borophosphates. Recently, it was found that borosilicates with the structure of a pentasil zeolite are very useful for dehydration of aldehyde.The results are summarized in Table 4.16. ... 

Table 4.16 Dehydration of aldehydes to dienes over borosilicatcs...

Molisch s Test. Dissolve about 01 g. of the carbohydrate in z ml. of water (for starch use 2 ml. of starch solution ), add 2-3 drops of a 1 % alcoholic solution of i-naphthol (ignoring traces of the latter precipitated by the water) and then carefully pour 2 ml. of cone. H2SO4 down the side of the test-tube so that it forms a heavy layer at the bottom. A deep violet coloration is produced where the liquids meet. This coloration is due apparently to the formation of an unstable condensation product of i-naphthol with furfural (an aldehyde produced by the dehydration of the carbohydrate). 

A reaction of great synthetic val ue for carbon-carbon bond for mation Nucleophilic addition of an enolate ion to a carbonyl group followed by dehydration of the 3 hydroxy aldehyde yields an a p unsaturated aldehyde... 

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... 

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. 

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 ... 

Hoffmaim-La Roche has produced -carotene since the 1950s and has rehed on core knowledge of vitamin A chemistry for the synthesis of this target. In this approach, a five-carbon homologation of vitamin A aldehyde (19) is accompHshed by successive acetalizations and enol ether condensations to prepare the aldehyde (46). Metal acetyUde coupling with two molecules of aldehyde (46) completes constmction of the C q carbon framework. Selective reduction of the internal triple bond of (47) is followed by dehydration and thermal isomerization to yield -carotene (21) (Fig. 10). 

Activated alumina and phosphoric acid on a suitable support have become the choices for an iadustrial process. Ziac oxide with alumina has also been claimed to be a good catalyst. The actual mechanism of dehydration is not known. In iadustrial production, the ethylene yield is 94 to 99% of the theoretical value depending on the processiag scheme. Traces of aldehyde, acids, higher hydrocarbons, and carbon oxides, as well as water, have to be removed. Fixed-bed processes developed at the beginning of this century have been commercialized in many countries, and small-scale industries are still in operation in Brazil and India. New fluid-bed processes have been developed to reduce the plant investment and operating costs (102,103). Commercially available processes include the Lummus processes (fixed and fluidized-bed processes), Halcon/Scientific Design process, NIKK/JGC process, and the Petrobras process. In all these processes, typical ethylene yield is between 94 and 99%. 

Other syntheses of oxiranes which are occasionally useful and involve a species (64) are the dehydration of 1,2-diols (Scheme 69) (78TL5153, 7808(58)12) and the reductive coupling of aldehydes (Scheme 70) (B-73MI50500). 

AljO cdn be used both as a base for the Henry reaction and as a dehydrating agent Thus, nitro ilkenes are simply prepared by mixing of aldehydes and nitro ilkanes with ATO and subsequent warming at 40 C fEq 3 30 ... 

Furfuryl dimethyl amine is first produced. This may conveniently be accomplished by employing the Leuckart synthesis known to those skilled in the art, which involves the use of an aldehyde or a ketone, and formate of ammonia or an amine, or corresponding formamide derived by dehydration of formate of ammonia or an amine. 

Conversion of the aldehyde into a nitrile is accomplished by treatment of an aldose with hydroxvlamine to give an oxime (Section 19.8), followed by dehydration of the oxJme with acetic anhydride. The Wohl degradation does not give particularly high yields of chain-shortened aldoses, but the reaction is general for all aldopentoses and aldohexoses. For example, D-galactose is converted by Wohl degradation into n-lyxose. 

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

There is no way in which dehydration of alcohols can be used to prepare triple bonds gem-diols and vinylic alcohols are not normally stable compounds and vic-diols give either conjugated dienes or lose only 1 mol of water to give an aldehyde or ketone. Dienes can be prepared, however, by heating alkynyl alcohols with triphenyl phosphine. ... 

Example Ester (59) was needed for a photochemical synthesis of chrysanthemate ester (60), a component of the pyrethrin insecticides. The a,B disconnection (59a) gives synthon (61) and aldehyde (62). This 8,y-unsaturated compound could be made by dehydration of (63) as the double bond can appear in only the required position. On page T 149 we discussed the synthesis of (62) by the aldol dimerisation of (64), An alternative strategy is to work at the ester oxidation level (65) which means synthon (66) is needed to combine with (64). 

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