Amines amide reduction

Fig. 17.66. Amide -> amine reduction (top) and lactam -> cycloamine reduction (bottom) with LiAlH..

The two specific examples shown in Figure 17.66 illustrate the general concept of the amide — amine reduction depicted in Figure 17.65. The reduction of a diamide to a diamine is shown on top, and the reduction of a lactam to a bicyclic amine is shown on bottom. 

R4N= BnEtsN or BU4N Heterocylces 1980, 14, 1437, 1441 reduction of amides to amines reduction of nitriles to amines... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Conversion of Amides into Amines Reduction Like other carboxylic acid derivatives, amides can be reduced by LiAlH.4. The product of the reduction, however, is an amine rather than an alcohol. The net effect of an amide reduction reaction is thus the conversion of the amide carbonyl group into a methylene group (C=0 —> CTbV This kind of reaction is specific for amides and does not occur with other carboxylic acid derivatives. 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Amides, macrobicyclic, reduction of, 54, 89 Amine oxides, anhydrous, 50,... 

An amide on reduction is changed to the corresponding amine and the order of the reactivity is RCONR2 > RCONHR > RCONH2. 

The amides on reduction with lithium aluminium hydride yield amines. 

Amines are prepared by aminolysis of alkyl halides, and also reductive amination (reduction in the presence of ammonia) of aldehydes and ketones (see Section 5.7.19). They are obtained conveniently from Hofmann rearrangement of amides. 

Notes A reducing agent. Alcohols are generated from aldehydes, ketones, esters and acid chlorides. Nitriles can be converted to aldehydes. Tosylates will be replaced by -H halides are inert. Amides are reduced to amines. Reduction of lactones can provide a useful synthetic strategy ... 

An alternative approach to synthesis of this ring system involves insertion of CO into the brominated secondary base (43), by treatment with carbon monoxide, lead tetra-acetate, and triphenylphosphine in tributylamine, the product being the amide (44), reduction of which affords the amine.81 Govadine (42 R1 = R4 = OMe, R2 = R5 = OH, R3 = H) has been synthesized by the conventional ring-closure, with formaldehyde, of the diphenolic base (45), or of its dibenzyl ether, in acid solution.82 Tetrahydroberberines, together with N-benzyltetrahydroisoquinolines, have also been obtained by the electrolytic reduction of 3,4-dihydroisoquinolines of structure (46).83... 

Oxidation-reduction (redox) reactions, along with hydrolysis and acid-base reactions, account for the vast majority of chemical reactions that occur in aquatic environmental systems. Factors that affect redox kinetics include environmental redox conditions, ionic strength, pH-value, temperature, speciation, and sorption (Tratnyek and Macalady, 2000). Sediment and particulate matter in water bodies may influence greatly the efficacy of abiotic transformations by altering the truly dissolved (i.e., non-sorbed) fraction of the compounds — the only fraction available for reactions (Weber and Wolfe, 1987). Among the possible abiotic transformation pathways, hydrolysis has received the most attention, though only some compound classes are potentially hydrolyzable (e.g., alkyl halides, amides, amines, carbamates, esters, epoxides, and nitriles [Harris, 1990 Peijnenburg, 1991]). Current efforts to incorporate reaction kinetics and pathways for reductive transformations into environmental exposure models are due to the fact that many of them result in reaction products that may be of more concern than the parent compounds (Tratnyek et al., 2003). 

Amides. An amide on reduction with lithium aluminum hydride is converted in good yield into the corresponding amine. The order of reuctivily Is RC ONR, > nr rfNHB > RCONH.. in a arocodura bv Maffiatl" for reduction of S.S dlmethyl ... 

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