4-Picoline, 3-amino-, amination

The reaction of isothiocyanate 2 and 30 with 2-amino-4-picoline has also been reported.55 Dorn and coworkers56"59 reported the synthesis of a number of substituted thioureido derivatives by treatment of isothiocyanates 2 and 5 with 2-phenylethylamine, bis(2-chloroethyl)amine, and 2-(4-ethoxyphenyl)-1 -phenylethylamine. 

Hydro acylation of alkenes was achieved in the presence of Wilkinson s catalyst and microwave irradiation under solvent-free conditions. As an example, benzaldehyde was reacted with dec- 1-ene to give 1-phenylundecan- 1-one in 83%yield within 30 min. Both domestic microwave ovens and single-mode reactors have been used for this reaction. The presence of an amine such as 2-amino-3-picoline or aniline and a carboxylic acid is crucial for the success of the reaction, showing that the formation of an imine plays an important role as an intermediate in the mechanism of this reaction29. 

A primary alcohol and amines can be used as an aldehyde precursor, because it can be oxidized by transfer hydrogenation. For example, the reaction of benzyl alcohol with excess olefin afforded the corresponding ketone in good yield in the presence of Rh complex and 2-amino-4-picoline [18]. Similarly, primary amines, which were transformed into imines by dehydrogenation, were also employed as a substrate instead of aldehydes [19]. Although various terminal olefins, alkynes [20], and even dienes [21] have been commonly used as a reaction partner in hydroiminoacylation reactions, internal olefins were ineffective. Recently, methyl sulfide-substituted aldehydes were successfully applied to the intermolecu-lar hydroacylation reaction [22], Also in the intramolecular hydroacylation, extension of substrates such as cyclopropane-substituted 4-enal [23], 4-alkynal [24], and 4,6-dienal [25] has been developed (Table 1). 

This two-step synthesis of ketones has been improved from the aldehyde into one-step synthesis with the cocatalyst system of the rhodium complex and 2-amino-3-picoline, which reacts with an aldehyde to give an aldimine in situ. The ketimine produced is easily converted to a ketone by in situ hydrolysis with H20, which is formed in the step of condensation of the aldehyde with the amine (Eq.56) [125]. 

The effect of temperature and pressure on the amination of 3-picoline is shown in Fig. 1. It is seen that the higher temperature gave lower yields of 2-amino-5-methylpyridine (53). This was probably due to thermolysis playing an important role. 

Butylamination of 3-picoline is shown in Scheme 35. The ratio of the 2-amino-5-isomer (89) to the 2-amino-3-isomer (90) was 16 L The yield of both isomers was 72%, which is about the same as obtained with sodium amide. The predominance of 89 is due most likely to steric hindrance caused by the bulkiness of the aminating agent. The situation is similar to the amination with sodium amide of 3-substituted pyridines at atmospheric pressure, in which the bulk of the 3-substituent directs the amount of 2-amino-5-isomer formed (Section IV), except that in this case, it is the size of the aminating group that decides the ratio of isomers. Additional alkylaminations of 3-substituted pyridines are shown in Table III. 

Another intramolecular synthesis of carbazoles 270 employed amino biaryls 269 as the starting materials with 2-picolinic acid as a directing group to facilitate a net C—H amination reaction under copper catalysis in the presence of Mn02 and acetic acid. The directing group is removed spontaneously after the initial amination (140L2892). 

Poly [ (amino) phosphazenes] have been synthetised by the replacement of chlorine atoms in poly[(dichloro)phosphazene] by amines (Allcock et al, 1966). Drug molecules bearing an amino-group are substituted in the same way, such as the anesthetic molecules procaine, benzocaine, chloroprocaine, butyl-p-aminobenzoyl and 2-amino-4-picoline (Allcock et al, 1982). The poly [(diamino) phosphazene] is not water soluble but this can be achieved by cosubstitution with methylamine, procaine or 2-amino-4-picolino. 

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