Aminoalcohols secondary

In an analogous sequence, reductive alkylation of aminoalcohol, 46, with cyclohexanone affords the secondary amine (47). Acylation with benzoyl chloride affords hexylcaine (48) in a reaction that may again involve acyl migration. 

Treatment of the piperidine 74, obtainable from an aminonitrile such as 73, under N-methylation conditions leads to the dimethylamino derivative 75. The carbobenzoxy protecting group is then removed by catalytic hydrogenation. Reaction of the resulting secondary amine 76 with cyclohexene oxide leads to the alkylated trans aminoalcohol. There is thus obtained the anti-arrhythmic agent transcainide (77) [18]. 

Thioacylation of primary and secondary amines, including aminoacids and aminoalcohols, has been readily carried out from phosphonodithioacetate 28 (R = Et) and the resulting phosphorylated thio amides (thio carbamoyl-... 

These results support our hypothesis that there is a retroaldol like cleavage of 3-hydroxynitrosamines which occurs in biological systems. Our results agree with the data of Kruger, Preussmann, and Blattmann. The fact that the tertiary nitros-aminoalcohols undergo the cleavage as well as their secondary counterparts demonstrates that oxidation to a ketone is not a... 

This reaction can be carried out in good yield with a wide variety of alcohols, phenols and, according to Hettche also with secondary and primary amines. Diols, diamines, or aminoalcohols lead to l,l-spiro-X -phosphorins. 

One of the first reports dealing with the carbozincation of alkenes by allylic organozinc reagents was the addition of allylzinc bromide to the homoallylic amine 118 which occurred in refluxing THF. A secondary organozinc 119 was regioselectively produced and provided the amine 120 after hydrolysis. A small amount of aminoalcohol 121, resulting from oxidation of 119, was also isolated when the reaction mixture was exposed to air (equation 52)80,81. 

Enantiomerically pure aminoalcohols, which are readily available by reduction of a-amino acids, can be converted into alkoxycarbonylating reagents suitable for the solid-phase synthesis of oligocarbamates (Figure 16.26). Particularly convenient alkoxycarbonylating reagents are 4-nitrophenyl carbonates, which can be prepared from alcohols and 4-nitrophenyl chloroformate, and which react smoothly with aliphatic primary or secondary amines to yield the corresponding carbamates. 

In 1981, Hirao and others reported that the chiral borane-amine complex 25a, derived from (S)-prolinol and 1 equivalent of BH3 THF, enantioselec-tively reduced propiophenone to afford (R )-l -phenyl-1 -propanol (26) in 44% ee9 (Scheme 4.3h). The chiral complex 25b was even better than 25a, affording the same secondary alcohol in 60% ee. Two years after the initial disclosure, Hirao et al. uncovered a new catalyst system that improved the previous experimental conditions dramatically10 (Scheme 4.3i). When the chiral aminoalcohol 27, prepared from (S)-valine methyl ester hydrochloride and phenylmagnesium bromide, was used along with 2 equivalents of BH3 THF, the enantioselectivity of the alcohol 26 jumped to 94% ee. In addition, the reaction time was shortened to 2 hours. 

Nu cyanide alkoxydes thiolates azoles ammonia primary amines secondary amines amino acids aminoalcohols... 

Asymmetric addition of diorganozincs to aldehydes catalyzed by chiral -amino alcohols provides a general method for the preparation of chiral secondary alcohols. Oguni, Noyori, and co-workers found that the aminoalcohol, (2S)-3-exo-(dimethylamino)isobornenol ((2S)-DAIB), acts as a particularly efficient promoter for this asymmetric reaction [9, 10]. Reaction of benzalde-hyde with diethylzinc in the presence of 2 mol% of (2S)-DAIB gives, after aqueous workup, (S)-l-phenylpropanol in high yield with 99% ee as shown in Scheme 8. Detailed mechanistic and theoretical studies of the (2S)-DAIB-pro-moted asymmetric addition have been reported [11]. 

The mechanism of all of the above mentioned reactions is essentially the same. However, some steps in the mechanism are still not fully understood. The following steps are believed to be involved in the Eschweiler-Clarke methylation 1) formation of a Schiff-base (imine) from the starting primary or secondary amine and formaldehyde via an aminoalcohol (aminal) intermediate 2) hydride transfer from the reducing agent (e.g., formic acid, cyanoborohydride, etc.) to the imine to get the corresponding A/-methylated amine along with the loss of CO2 and 3) if the starting amine was primary, then steps 1 and 2 are repeated. 

This procedure enabled versatile hydrolysis of pyrrohdinones followed by decarboxylation (Scheme 12.191) [347]. It has been disclosed that a neutral organotin dimer [tBu2SnOH(Cl)]2 is an efficient catalyst for deacetylation (Scheme 12.192) [348]. When an MeOH solution of an acetate was heated at 30 °C in fhe presence of a catalytic amount of the organotin dimer deacetylation proceeded quite smoothly to furnish the parent alcohol, in which a variety of acid-labile functional groups remained intact. Acetates of primary alcohols and phenols underwent rapid deacetylation whereas acetates of secondary alcohols reacted only sluggishly. When fhis deacetylation procedure was apphed to acetates derived from tertiary alcohols fhey remained intact, and decomposed under harsher conditions. When nonracemic acetates derived from chiral alcohols and aminoalcohols were treated wifh [tBu2SnOH(Cl)]2 in MeOH, the desired deacetylation proceeded, and no racemization was observed. Exclusive deacetylation of primary alcohols in fhe reaction of peracetates of carbohy-... 

When a -aminoalcohol containing a secondary amino group was used the primary amine was obtained, with slight loss of optical purity (Scheme 13.54) [73 b]. 

Nitrogenous bases useful in my process include ammonia, either as liquid ammonia or as ammonium hydroxide, and hydrazine primary amines, such as ethylamine, glycine, propylamine, aniline, and the like, secondary amines, such as morpholine, diphenylamine, methylaniline, diethylamine, and the like aminoalcohols, such as 2-aminopropan-l-ol, isovalinol, ephedrine, 2-(N-benzylamino)-propan-l-ol, and the like. A specific aminoalcohol, l-(+)-2-aminopropan-l-ol, is especially usefully employed in my invention since its reaction with the mixed anhydride of d-lysergic and sulfuric acids produces the pharmacologically active... 

A new process for synthesis of 3-aminomethyl-3,5,5-trimethylcyclohexylamine (IPDA) has been investigated. The reaction was performed in two steps. In the first step bis (3-cyano-3,5,5 trimethylcyclohexylidene) azine (IPNA) was synthesized from 3-cyano-3,5,5 trimethyl- 1 oxo cyclohexane (IPN) and hydrazine hydrate in solvent. The reaction yield was nearly quantitative. In the second step the azine (IPNA) was hydrogenated under mild conditions on a Raney nickel or cobalt catalyst in the presence of a small amount of ammonia. Isophorone diamine (IPDA) was obtained at high yields (90-95 %). But the main interest of a such process is to minimize the production of byproducts (aminoalcohol, azabicyclic compound, secondary amine) and to use less severe pressure conditions than those generally employed. 

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