Interesting and Useful Amines

A great many simple and complex amines occur in nature, and others with biological activity have been synthesized in the lab. 

Many low molecular weight amines have very foul odors. Trimethylamine [(CH3)3N], formed when enzymes break down certain fish proteins, has the characteristic odor of rotting fish. Putrescine (NH2CH2CH2CH2CH2NH2) and cadaverine (NH2CH2CH2CH2CH2CH2NH2) are both poisonous diamines with putrid odors. They, too, are present in rotting fish, and are partly responsible for the odors of semen, urine, and bad breath. 

The word alkaloid is derived from the word a/ka/z because aqueous solutions of alkaloids are slightly basic. 

NH2 Histamine, a rather simple triamine first discussed in Section 17.8, is responsible for a wide 

Three common alkaloids— Atropine, nicotine, and coniine 

The CH3 group appears as a singlet at 2.7 ppm because there is no splitting by the adjacent NH proton. 

The five H atoms of the aromatic ring appear as a complex pattern at 6.6-T.2 ppm. 

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An interesting and useful property of enamines of 2-alkylcyclohexanones is the fact that there is a substantial preference for the less substituted isomer to be formed. This tendency is especially pronounced for enamines derived from cyclic secondaiy amines such as pyrrolidine. This preference can be traced to a strain effect called A or allylic strain (see Section 3.3). In order to accommodate conjugation between the nitrogen lone pair and the carbon-carbon double bond, the nitrogen substituent must be coplanar with the double bond. This creates a steric repulsion when the enamine bears a p substituent and leads to a... 

As a result of the hydridic nature of the hydrogen attached to boron, amine-boranes are interesting and useful reducing agents and have been employed in the reduction of numerous organic carbonyl compounds. They have been utilized in studying the kinetics and mechanism of hydride reactions and are precursors for the synthesis of substituted boranes, borazines, boronium ions, higher boron hydrides, and carboranes. 

Aldol reactions. In conjunction with an amine, dicyclohexylboron chloride is used to generate kinetic enolates from ketones. Some interesting and useful information concerns the stereoselectivity of the aldol reactions. ... 

The functionalizations of nucleosides are also of continuous interest when using amination technology, and Lakshman reported several interesting applications in this research area [167]. 

An interesting and useful property of enamines of cyclohexanones is the fact that there is a substantial preference for the less substituted isomer to be preferred. This tendency is especially pronounced for enamines derived from cyclic secondary amines. 

Although the emphasis in this chapter has been on tbe synthesis and mechanism of formation of simple enamines, brief mention will be made of the addition of amines to activated acetylenes to indicate the interest and activity in this area of substituted enamines. Since such additions tend to be stereospecific, inclusion in this section seems apropos. The addition of amines to acetylenes has been much studied 130), but the assigning of the stereochemistry about the newly formed double bond could not be done unequivocally until the techniques of NMR spectroscopy were well developed. In the research efforts described below, NMR spectroscopy was used to determine isomer content and to follow the progress of some of the reactions. 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

The coupling between an aryl halide or triflate and an amine is known as the Buchwald-Hartwig amination [138]. Originally it was described using a tributyltin amine [139,140] and was thus considered to be a coupling reaction. Subsequently, tributyltin amine was replaced by a standard amine and a strong base. It is a reaction of great academic and industrial interest [11]. 

The Schiff bases being derivatives of aldehydes or ketones and various amines have received considerable attention because of their interesting physical and chemical properties, involvement in biologically important reactions and widespread application of their metal complexes. Increasing interest in optically active Schiff bases is connected with the discovery at the beginning of the 1990s of the so-called Jacobsen catalysts used in several asymmetric reactions showing excellent enantioselectivity. 

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