Dehydrogenation of amino alcohol

Dehydrogenation of amino alcohols of type 40 affords even bicyclic compounds 41, the formation of which can be explained by nucleophilic attack of the hydroxyl group on the formed enamine salt (133,134). 

If other groups are present in the base subjected to the dehydrogenation, subsequent reactions can take place. Thus, dehydrogenation of amino-alcohols leads to aza-oxa compounds.182,183... 

Dialkylaminomethyl alkyl (and aryl) sulfides result from the treatment of a-halogeno-amines with mercaptans (thiophenols).325 Dehydrogenation of amino-alcohols with mercuric acetate182,328 is accompanied by the intramolecular nucleophilic addition of the alkoxyl group when formation of a five- or six-membered ring is possible, e.g. ... 

Some industrial organic synthesis reactions take place in the presence of aqueous caustic soda. A typical exanqile is the dehydrogenation of amino alcohols to amino carboxylic acid salts, which is typically conducted at 1.0 MPa and 393K-483K in a concentration of caustic up to 50wt%. Under such harsh conditions, most supported copper catalysts cannot be used due to dissolution of... 

The stability of the chromia promoted skeletal Cu in highly concentrated caustic solution at temperature around 400K indicates significant potential for use in organic synthesis reactions such as the dehydrogenation of amino alcohols to carboxylic acid salts. 

Symmetrical pyrazines may be accessed by the dimerisation of vicinal amino alcohols (Scheme 12.35). Milstein discovered that a ruthenium PNP pincer complex catalyses the acceptorless dehydrogenation of amino alcohols in toluene at reflux, likely inducing double condensation to a dihy-dropyrazine which may undergo an additional dehydrogenation to provide the observed products. A similar Ru-PNN pincer complex, possessing a hemi-labile amine arm, was found to catalyse the conversion of amino alcohols to diketopiperazines (see Section 12.2.2)... 

Scheme 12.34 Dehydrogenative condensation of amino alcohols with alcohols.

Amino alcohols (33) were transformed to ketones on copper.360 361 The transformation involves the dehydrogenation of the hydroxyl group, the elimination of dimethylamine, and the hydrogenation of the unsaturated ketone (Scheme 4.111). 

Figure 1. First order plots based on hydrogen evolution for the oxidative dehydrogenation of ethanolamine (EA), 2-(2-aminoethylamino)ethanol (AEAE), 3-amino-1-propanol (AP), 2-(methylamino)ethanol (MAE) and benzyl alcohol (BA) over chromia-promoted copper.

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). 

Conversion of dihydroxy compounds to diamines requires the repetition of all reaction steps (dehydrogenation, addition, elimination, hydrogenation). Selectivity is much higher when diols are transferred only to amino alcohols or amino alcohols to diamines. This difference is exemplified by the reaction of 1,6-hexanediol with di-methylamine over CU/AI2O3 [25]. Over 90% selectivity for the intermediate N,N-dimethyl-6-amino-l-hexanol was achieved at 180 °C in a continuous fixed-bed reactor. To complete the amination of the second OH group the reactor temperature had to be raised to 230 °C and the highest selectivity for diamine was only 65 %. 

Dehydrogenation of primary amino groups introduces, again in analogy to alcohols, a... 

Crabtree and co-workers discovered the dehydrogenative Paal-Knorr synthesis the reaction of 1,4-diols with primary amines in the presence of a Ru diphosphine diamine complex at 125 °C to afford 2,5-disubstituted pyrroles (Scheme 12.37)." Kempe and Milstein developed dehydrogenative conditions for the synthesis of pyrroles via C-N and C-C coupling of alcohols with vicinal amino alcohols (Scheme 12.37). These reactions require the use of KOfBu, which may facilitate a-deprotonation of the intermediate imine. 

Consequently, by choosing proper conditions, especially the ratios of the carbonyl compound to the amino compound, very good yields of the desired amines can be obtained [322, 953]. In catalytic hydrogenations alkylation of amines was also achieved by alcohols under the conditions when they may be dehydrogenated to the carbonyl compounds [803]. The reaction of aldehydes and ketones with ammonia and amines in the presence of hydrogen is carried out on catalysts platinum oxide [957], nickel [803, 958] or Raney nickel [956, 959,960]. Yields range from low (23-35%) to very high (93%). An alternative route is the use of complex borohydrides sodium borohydride [954], lithium cyanoborohydride [955] and sodium cyanoborohydride [103] in aqueous-alcoholic solutions of pH 5-8. 

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