Amide oximes reduction

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

A number of organic species, including amides, oximes, and nitriles, undergo reductive amination, a variety of reduction reactions that produce cimines. In general, these processes involve imines, R=N-R, or related species. Reduction processes include hydrogenation using Raney nickel as the catalyst (for nitriles), the reaction with sodium/EtOH (for oximes), and the use of lithium aluminum hydride, LiAlH (for amides or nitriles). Figure 13-16 illustrates the preparation of amphetamine by reductive amination. 

The reduction of a number of nitrogen derivatives such as amides, oximes, alkyl cyanides or nitro compounds, particularly with lithium aluminium hydride, provides useful ways of making amines. The value of these methods lies in the fact that these derivatives allow the nitrogen to be introduced into a compound at different oxidation levels (Scheme 2.30a). 

Amines may be prepared by the nucleophilic substitution of alkyl halides with ammonia or other amines, by the reduction of imines, nitriles, amides, oximes or nitro compounds or by the rearrangement of amides. 

Aromatic amide oximes are reduced in acid solution similarly to other reducible derivatives of hydroxylamine [1,99] the first step is a reductive loss of oxygen. The reduction of benzamide oxime thus yields benzamidine [1] ... 

The reduction of derivatives of hydroxylamine involves splitting of the N-O bond. It has been shown [229] that the cleavage of the N-O bond in oximes generally occurs prior to the saturation of the double bond. In alkaline solution at low temperature, however, some reduction of an aldoxime to a hydroxylamine takes place. A similar primary cleavage of an N-O bond is found in the reduction of amide oximes [229] and hydroxamic acids [236]. The reduction of oximes in acid solution has been formulated as Eq. (61) ... 

Metal Hydrides. A number of patents and publications have appeared describing the use of lithium aluminum hydride in the reduction of nitro compounds, nitriles, amides, oximes, and azides to amines. Moderate to high yields have been obtained. This process is useful in the selective reduction of compounds sensitive to catalytic hydrogenation, but is quite costly. 

PRACTICE PROBLEM 20.6 Show how you might utilize the reduction of an amide, oxime, or nitrile to carry out... 

Alcohols from oxo compds. 20 eqs. NaBH4 added to a soln. of 5 eqs. ZrC in THF at room temp, under N2, a soln. of 4 eqs. acetophenone in the same solvent added, and the mixture stirred at room temp, for 5 h - 1-phenylethanol. Y 96%. ZrCl4 is inexpensive, easy to use, and does not affect ar. nitro compds. and bromides. F.e., also reduction of carboxylic acids, esters and halides to prim, alcohols, and amides, oximes, alkoximes, nitriles, and imines to amines, s. S. Itsuno et al.. Synthesis 1988, 995-6. 

Preparation of amines through reduction of amides, oximes, and nitriles. 

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

Most aminothiophenes are prepared by the reduction of nitrothio-phenes. Aminothiophenes or their derivatives have also been obtained through the Hofmann rearrangement of the acid amides, which, however, fails with 2-thenamide, in contrast to the 3-isomer. The Beckmann rearrangement of the oxime of 2-acetylthiophene has been applied successfully to the preparation of 2-acetamidothiophene. The free aminothiophenes are very unstable compounds and it has not been possible to distil 3-aminothiophene. They are best stored as the stannic-chloride double salts and give stable acetyl derivatives. 

A variant on this structure, dioxyline, has much the same activity as the natural product but shows a better therapeutic ratio. Reduction of the oxime (113) from 3,4-dimethoxyphenyl-acetone (112) affords the veratrylamine homolog bearing a methyl group on the amine carbon atom (114). Acylation of this with 4-ethoxy-3-methoxyphenyl acetyl chloride gives the corresponding amide (115). Cyclization by means of phosphorus oxychloride followed by dehydrogenation over palladium yields dioxyline (116). ... 

Oxidative cleavage of amines 9-39 Reduction of amides 9-47 Reduction of nitro compounds 9-50 Reduction of nitroso compounds or hydroxylamincs 9-51 Reduction of oximes 9-52 Reduction of azides 9-53 Reduction of isocyanates, isothiocyanates, or N-nitroso compounds 9-55 Reduction of amine oxides 9-59 Reduction of azo, azoxy, or hydrazo compounds... 

Amide reduction with lithium aluminum hydride, 39, 19 Amine oxide formation, 39, 40 Amine oxide pyrolysis, 39, 41, 42 -Aminoacetanilide, 39, 1 Amino adds, synthesis of, 30, 7 2-Amino-4-anilino-6-(chloro-METHYl) -S-TRIAZINE, 38, 1 -Aminobenzaldehyde, 31, 6 hydrazone, 31, 7 oxime, 31, 7 phenylhydrazone, 31, 7 > -Aminobenzoic add, 36, 95 2-Aminobenzophenone, 32, 8 c-Aminocaproic acid, 32, 13 6-Aminocaproic acid hydrochloride,... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

---