Oxidation secondary amine

Figure 4 Representative illustrations of primary amine oxidation (A), secondary amine oxidation (B), tertiary amine oxidation (C), and xenobiotics that undergo N-hydroxylation or oxidation reactions (D).

Deoxynortryptoquivaline is also a secondary amine, oxidation of which leads to (105). 

Similarly, the secondary amine oxides formed with oxygen and/or peroxide, having rearranged to the corresponding hydroxylamines are subsequently oxidized further with, for example, silver oxide (Ag20) in ether, to produce stable free... 

Primary and secondary amines are susceptible to oxidation and replacement reactions involving the N—H bonds. Within the development of peptide synthesis numerous protective groups for N—H bonds have been found (M, Bodanszky, 1976 L.A. Carpino, 1973), and we shall discuss five of the more general methods used involving the reversible formation of... 

Acetylene is also protected as propargyl alcohol (300)[2H], which is depro-tected by hydrolysis with a base, or oxidation with MnOi and alkaline hydrolysis. Sometimes, propargyl alcohols are isomerized to enals. Propargyl alcohol (300) reacts with 3-chloropyridazine (301) and EtiNH to give 3-diethylami-noindolizine (303) in one step via the enal 302[2I2]. Similarly, propargyl alcohol reacts with 2-halopyridines and secondary amines. 2-Methyl-3-butyn-2-ol (304) is another masked acetylene, and is unmasked by treatment with KOH or NaOH in butanol[205,206,213-2l5] or in situ with a phase-transfer cata-lyst[2l6]. 

Metal Catalysis. Aqueous solutions of amine oxides are unstable in the presence of mild steel and thermal decomposition to secondary amines and aldehydes under acidic conditions occurs (24,25). The reaction proceeds by a free-radical mechanism (26). The decomposition is also cataly2ed by V(III) and Cu(I). 

Primary and secondary amines are oxidized to the respective hydroxyl amines, and further oxidation to the nitro compound occurs ia the case of primary amines. 

Ethoxylation and Propoxylation. Ethylene oxide [75-21-8] or propylene oxide [75-56-9] add readily to primary fatty amines to form bis(2-hydroxyethyl) or bis(2-hydroxypropyl) tertiary amines secondary amines also react with ethylene or propylene oxide to form 2-hydroxyalkyl tertiary amines (1,3,7,33—36). The initial addition is completed at approximately 170°C. Additional ethylene or propylene oxide can be added by using a basic catalyst, usually sodium or potassium hydroxide. 

Ammonia, and Amines. Isopropanolamine is the product of propylene oxide and ammonia ia the presence of water (see Alkanolamines). Propylene oxide reacts with isopropanolamine or other primary or secondary amines to produce A/- and A/,A/-disubstituted isopropanolamines. Propylene oxide further reacts with the hydroxyl group of the alkanolamines to form polyether polyol derivatives of tertiary amines (50), or of secondary amines ia the presence of a strong base catalyst (51). 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

N-Unsubstituted pyrazoles and imidazoles add to unsaturated compounds in Michael reactions, for example acetylenecarboxylic esters and acrylonitrile readily form the expected addition products. Styrene oxide gives rise, for example, to 1-styrylimidazoles (76JCS(P1)545). Benzimidazole reacts with formaldehyde and secondary amines in the Mannich reaction to give 1-aminomethyl products. 

Primary and secondary amines, double bonds, aldehydes, sulfides and certain aromatic and dihydroaroraatic systems are also oxidized by chromium VI reagents under standard hydroxyl oxidizing conditions. Amines are commonly protected by salt formation or by conversion to amides. Aldehydes and... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

The most versatile method for preparing enamines involves the condensation of aldehydes and ketones with secondary amines [Eq. (1)]. Mannich and Davidsen (/) discovered that the reaction of secondary amines with aldehydes in the presence of potassium carbonate and at temperatures near 0° gave enamines, while calcium oxide and elevated temperatures were required to cause a reaction between ketones and secondary amines, although usually in poor yield. The introduction by Herr and Heyl 2-4) of the removal of the water produced in the condensation by azeotropic distillation with benzene made possible the facile preparation of enamines from ketones and disubstituted aldehydes. 

The cyclic thioketone, 3-oxotctrahydrothiophene (11), gives a mixture of enamines (12,13) when caused to react with a secondary amine such as piperidine or pyrrolidine (31). The enamine mixture can be reduced to the 3-aminotetrahydrothiophene using formic acid or oxidized to the 3-amino-thiophene using diisopentylsulfide. 

The reduction was studied in more detail by Cook and Schulz (52). They demonstrated conclusively that reduction of iminium salts by secondary amines is possible as illustrated in Eqs. (7) and (8). The oxidation... 

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