Aldehydes reaction with hydroxylamine

The product (15-2) from aldol condensation of meto-nitrobenzaldehyde with the dimethyl acetal from ethyl 4-formylacetoacetate (15-1) provides the starting material for a dihydropyridine in which one of the methyl groups is replaced by a nitrile. Reaction of (15-2) with the eneamine from isopropyl acetoacetate gives the corresponding dihydropyridine hydrolysis of the acetal function with aqueous acid affords the aldehyde (15-3). That function is then converted to its oxime (15-4) by reaction with hydroxylamine. Treatment of that intermediate with hot acetic acid leads the oxime to dehydrate to a nitrile. There is this obtained nilvadipine (15-5) [16]. 

Nitriles. Aldehydes can be converted directly in satisfactory yield into nitriles by reaction with hydroxylamine hydrochloride at 90-140° when N-methylpyrrolidone is used as solvent. 

Reaction with hydroxylamine occurs on the aldehyde group of the more reactive minor tautomer 4.43 affording isoxazole 4.44. Methoxide-induced fragmentation as shown gives enolate 4.48 which is quenched by a proton in the workup to afford 2-cyanocyclohexanone 4.45. 

Aldehydes enter into important reactions of another type. The reaction with hydroxylamine is an example. When an aldehyde is warmed with an aqueous solution of this reagent a substance is formed which belongs to the class known as aldoximes. Acetaldehyde gives acetoxime —... 

Solution A characteristic of both ketones and aldehydes is the carbonyl functional group they possess. Thus, to characterize and identify ketones and aldehydes, reactions with the carbonyls are often done. Since oxygen is more electronegative, (electron-attracting) than carbon, the carbonyl carbon becomes susceptible to nucleophilic attack. Hydroxylamine, derived from its hydrochloride salt, can act as a nucleophilic reagent. 

Oxone has also been recently more thoroughly studied as reagent for the oxidation of aldehydes. Aryl- and aliphatic aldehydes can be efficiently converted directly to acids or esters depending on the choice of solvent (eq 34). They can also be converted to nitriles in one pot by reaction with hydroxylamine on alumina with microwave irradiation (eq 35). ... 

This reaction was initially reported by Granacher in 1922. It is the preparation of thionic acid by the treatment of Aldol Condensation product from an aldehyde and rhodanine with a base (e.g., NaOH). Therefore, this reaction is known as the Granacher synthesis or Granacher reaction." The prepared thionic acid in this reaction can be further converted into a variety of derivatives under different conditions. For example, it can be transformed into a-thiol acid under a basic sodium amalgam reduction, whereas aliphatic acid is formed under an acidic zinc amalgam reduction. In addition, when the thionic acid is treated with ammonia, a-keto acid is generated, and the thionic acid can be converted into af-carboxyl oxime in reaction with hydroxylamine, from which either cy-amino acid or aliphatic nitrile forms via the treatment of sodium amalgam reduction or acetic anhydride, respectively. 

In Section 18-16, we saw that amines attack ketones and aldehydes. When this nucleophilic attack is followed by dehydration, an imine (Schiff base) results. The analogous reaction of a hydrazine derivative gives a hydrazone, and the reaction with hydroxylamine gives an oxime. In Section 19-19, we will use these reactions to synthesize amines. 

Oximes prepared from aldehydes or ketones by reaction with hydroxylamine can be reduced to primary amines in high yields. One can use various reagents for the reduction step, including Ni-H2 in methanol or L1A1H4 in ether. Using a reduction reaction, carry out the following transformations ... 

This conversion is generally achieved by converting the aldehyde into oxime followed by its dehydration by a variety of reagents. One pot synthesis has also been developed , but these methods suffer from a number of drawbacks. In the microwave assisted reaction, the aldehyde is converted into oxime by reaction with hydroxylamine hydrochloride and potassium fluoride on alumina... 

Determination of carbonyl groups by reaction with hydroxylamine hydrochloride and titration of the liberated hydrochloric acid, or determination of aldehyde groups by oxidation with hypoiodite or chlorous acid and by reaction with diamines and subsequent fixation of dyes. 

Compounds such as hydroxylamine and hydrazine are similar to primary amines in that they have an NH2 group. Thus, like primary amines, they react with aldehydes and ketones to form imines—called imine derivatives because the substituent attached to the imine nitrogen is not an R group. The imine derivative obtained from the reaction with hydroxylamine is called an oxime, and the imine derivative obtained from the reaction with hydrazine is called a hydrazone. 

Diels-Alder reaction of 2-bromoacrolein and 5-[(ben2yloxy)meth5i]cyclopentadiene in the presence of 5 mol % of the catalyst (35) afforded the adduct (36) in 83—85% yield, 95 5 exo/endo ratio, and greater than 96 4 enantioselectivity. Treatment of the aldehyde (36) with aqueous hydroxylamine, led to oxime formation and bromide solvolysis. Tosylation and elimination to the cyanohydrin followed by basic hydrolysis gave (24). 

Oxime (Section 17.10) A compound of the type R2C=NOH, formed by the reaction of hydroxylamine (NH2OH) with an aldehyde or a ketone. 

To synthesize 3-substituted isoxazoles directly, Kochetkov and Khomutova have used the reaction of ethyleneacetals of )S-keto-aldehydes (readily available from jS-chlorovinylketones) with hydroxylamine. Owing to the comparative stability of the dioxolane group, this reaction yields unequivocally the pure 3-substituted isomers (22—>23). The use of noncyclic alkyl )S-ketoacetals in this reaction results in a mixture of 3- and 5-substituted isomers. ... 

The addition of (E)- and (Z)-crotylboronates 7 to aldoximes 6 has been realized in good yield by performing the reaction under 3-6 x 10° Torr pressure10. The resulting hydroxylamines 8 can easily be reduced to yield the primary amines. The addition of E-l leads preferentially to the anh-diastereomcr 8, while (Z)-crotylboronate 7 shows a modest selectivity towards formation of the vyy -diastereomer 8 (same sense as in the reaction with aldehydes). Some effort has been made to elucidate the mechanism, but this is not yet well understood. 

The reaction of 2-chloro-4,5-dihydroimidazole 347 with hydroxylamine-O-sulfonic acid gives 2-hydroxylamino-4,5-dihydroimidazolium-O-sulfonate 348, which reacts with aldehydes and cyclic ketones to give the imidazo[l,2-f] fused 4,5-dihydro-l,2,4-oxadiazoles 350 (Scheme 58). Mechanistically, the reaction may be explained by the reaction of an imidazoline NH with the carbonyl followed by intramolecular electrophilic amination of the anionic oxygen present in the resultant intermediate 349 and elimination of the sulfate group <2003JOC4791>. 

Table 2.5 Formation of optically active functionalized fS-hydroxy-nitroncs 95 by reaction of aldehydes 93 with activated carbonyl compounds 94 and substituted N -alkyl hydroxylamine hydrochloride in the presence of L-proline as the catalyst...

This procedure is an adaptation of that described by Emmons for the preparation of oxaziranes from imines using peracetic acid. Other procedures which may be more useful for oxazirane preparation in specific instances are the oxidation of imines with iw-chloroperbenzoic acid and the reaction of aldehydes or ketones with hydroxylamine 0-sulfonic acid in alkaline solution. 2-<-Butyl-3-phenyloxazirane has also been prepared by photolysis of a-phenyl-N-f-butylnitrone (a general reaction of considerable theoretical interest since it represents direct conversion of electromagnetic energy to chemical energy) and in low yields by ozonoly-sis of N-f-butylbenzaldimine. ... 

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