Polyfunctional amino-compounds

III. Amines and polyfunctional amino-compounds (amino-acids etc.). Salts of amines. 

The chapters are organized for easy reference and incorporate tables by which information on specific compounds can be readily traced. Table entries on individual compounds are listed in order of their molecular formula. We suggest that a molecular formula check is the surest way of ascertaining if a particular compound is listed in the tabulation. Also, a molecular formula provides a convenient search term for locating specific information in Chemical Abstracts. It is clearly impossible to include the entries for polyfunctional compounds in each appropriate table so that in the case, for example, of a chloroamino compound the tabulation of both chloro- and amino compounds must be consulted. 

This is another, but simpler, case of the many which are clarified by writing a material balance and reducing it to a function of one variable. Many polyfunctional organic compounds, as well as inorganic compounds having an ampholyte ion, show low solubility in water but become more soluble in both acidic and basic solution. Amino acids and CaHP04 are examples. Data are available for... 

Except for some polyfunctional aromatic amino-compounds (e.g. aminophenols, some amino-acids, phenylenediamines) aromatic amines are not soluble in water. Most dissolve in dilute hydrochloric acid, but some weak bases, e.g. nitroanilines, diphenylamines and polyhalogeno-anilines dissolve only in concentrated acids. A few aromatic amines (e.g. naphthylamines) dissolve in concentrated hydrochloric acid and then slowly precipitate as their sparingly soluble hydrochlorides. In all cases of doubt as to the solubility of a suspected amine in hydrochloric acid, a little of the filtered solution should be treated with an excess of alkali, when the amine (if insoluble in water) should be regenerated as an oil or solid. Amino-phenols and amino-acids are amphoteric substances (see pages 14-76). 

It was only around 1850 that the first amines were discovered by Wurtz [2], who considered them as alkylated (or arylated) derivatives of NH3. Nowadays, it is well known that the amine function is widespread among biologically important compounds, but mostly it is present in polyfunctional molecules such as amino acids, alkaloids, etc. Simple amines are very rare in nature, with the exception of tri-ethylamine and the trimethylammonium ion which come from the putrefaction of proteins. 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

These reagents in the presence of a solvent (such as pyridine, acetonitrile, dimethylformamide) rapidly effect trimethylsilylation, often at room temperature, of hydroxyl, amino, imino, amido, thiol and carboxyl groups whether in mono- or polyfunctional compounds. Frequently a sample of the reaction mixture may be loaded directly on to the g.l.c. column, although in some cases removal of the small amount of solvent which is present may improve subsequent analysis of the chromatographic trace. Proprietary reagent formulations are available from Pierce Chemical Co., pioneers in this field and publishers of detailed procedures suited to particular groups of compounds. 

Based on the very different behaviors of lipases A (CAL-A) and B (CAL-B) from Candida antarctica towards polyfunctional compounds in non-aqueous media, Liljeblad et al82 reported a novel lipase-catalyzed method for the resolution of A -heterocyclic amino esters using methyl pipecolinate 69 as a model compound. For this purpose, the chemo-and enantioselective alcoholysis and transesterification reaction of 69 in the presence of CAL-B and the A-acylations using CAL-A were studied, (cf. fig. 37 and 38). 

As far as the shape and size of the molecules are concerned, direct Mannich synthesis or typical reactions of Mannich bases, such as amino group replacement, open up the possibility of producing derivatives that have the chemical structures 1-VII (Fig. 182). Examples of such derivatives are compounds 494—503, all selected from products that have properties with useful practical applications. Thus, nonsymmetrical molecules with different A and B functionalities (type I in Fig. 182), along with symmetrically disubstituted molecules (type II), cyclic or branched compounds (types III and IV), as well as polymeric or crosslinked derivatives (types V-VII), can be produced as the result of appropriate combinations of mono- or polyfunctional A and B reactants. 

By analogy to halolactonization, a methodology termed cyclocarbamation has been developed for the functionalization of double bonds. The stereoselective introduction of polyfunctional moieties, such as amino alcohols, starting from cyclic and acyclic substrates has been studied with the aim of synthesizing biologically active compounds. 

The exchange of halogen for the amino group is important in the formation of other polyfunctional compounds, particularly the amino acids. In several of these transformations with aqueous or liquid ammonia, it has been shown that the presence of ammonium salts minimizes the formation of secondary and tertiary aminesExcellent directions for the synthesis of a-amino acids (C,-C ) from a-halo acids and ammonia are given. The methods have been reviewed. Long-chain amino acids are prepared by this and other procedures. ... 

The sensitivity of Si chemical shifts to structural changes and the technique of silylating compounds for more favourable analysis or synthesis have been combined by several researchers to produce a powerful structure elucidation technique for monofunctional or polyfunctional compounds. (135-141) Specifically, the trimethylsilyl derivatives of imidophosphoryl compounds, (141) sugars, (138-140) steroids, (140) amines, amides, and urethanes, (135,136) and amino-, hydroxy-, and mercaptocarboxylic acids (137) have all been studied within the past three years. 

A polyfunctional organic molecule can contain many different kinds of functional groups, but for nomenclature purposes, we must choose just one suffix. It s not correct to use two sufhxes. Thus, keto ester 3 must be named either as a ketone with an -one. suffix or as an ester with an -oate suffix but can t be named as an -onoate. Similarly, amino alcohol 4 must be named either as an alcohol (-ol) or as an amine i-amine) but can t properly be named as an -olamine. The only exception to this rule is in naming compounds that have double or triple bonds. For example, the unsaturated acid H2C=CHCH2C00H is 3-butenoic acid, and the acetylenic alcohol HCSCCH2CH2CH2CH2OH is 5-hexyn-l-ol. 

The macrolide lactone antibiotics are isolated primarily from the genus Streptomyces. Their antibacterial activity is mostly in the Gm+ spectrum. They are classified on the basis of the size of the macrocyclic lactone rings, the aglycone component of the compound. These are 12-, 14-, or 16-membered rings, glycosidically linked to one or more amino sugars, thus making these polyfunctional compounds basic (Fig. 6-25). 

Some special derivatization methods that lead to the formation of cyclic products were recommended for alcohols with more than two hydroxyl groups in the molecule (polyols including carbohydrates), amino alcohols, and polyfunctional aromatic hydroxy compounds. An appropriate arrangement of two functional groups [(OH)2, (OH) + (NH2) or (OH) + (CO2H)] in 1,2 (vie) 1,3 or ortho (in aromatic series) positions is necessary for their realization (Table 8). 

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