Imines 3-amino

Recently, scandium triflate [Sc(OTf)3] was found to be stable in water and successful Lewis acid catalysis was carried out in both water and organic solvents [6-8]. Sc(OTf)3 coordinates to Lewis bases under equilibrium conditions, and thus activation of carbonyl compounds using a catalytic amount of the acid has been achieved [6,7]. In addition, effective activation of nitrogen-containing compounds such as imines, amino aldehydes, etc. has been performed successfully [8]. Encouraged by the characteristics and the usefulness of Sc(OTf)3 as a Lewis acid catalyst, a polymer-supported scandium catalyst was prepared. 

Amino complexes. The yd-H elimination from a coordinated amine has been observed for [Os(NH3)4L(NH2Pr)] + (L = CH3CN, MeOH) to give the imine hydrido species [OsH(NH3)4 r/ -NH2=CH(CH2CH3) ] +. The reverse reaction, insertion of the imine into the Os-H bond, is also observed and the equilibrium constant is estimated as A = [hydrido-imine]/[amino] = 10" at 25°C (Scheme 6.31) [101]. The structure of a related complex [Mo(H)(r7 -Me2C=NAr)(N PrAr)2] (Ar = 3,5-C6H3Me2) has been crystallographically determined [102]. 

The nucleophilicity of amine nitrogens is also differentiated by their environments. In 2,4,5,6-tetraaminopyrimidine the most basic 3-amino group can be selectively converted to a Schiff base. It is meta to both pyrimidine nitrogens and does not form a tautomeric imine as do the ortho- and /xira-amino groups. This factor is the basis of the commercial synthesis of triamterene. 

Rj = H, R2 = COOH) and isobetanidine (96, R2 = H, Rj = COOH). Furthermore, it would appear that all betacyanins or betaxanthins may simply be imine derivatives (with the appropriate amino acid) of betalamic acid (97). 

Chlorosulfonyl isocyanate is an excellent alternative to alkaline cyanates ia the preparation of hydantoias from stericaHy hindered or labile amino nitriles (62). Imino derivatives similar to (18) can also be obtained by addition of sonitnles to imines followed by treatment with a cyanate (63). 

The 6-methoxymethylene penicillanic acid [93040-42-7] (31, R = CH OCH (2)-isomer, R" = R " = 3) designed to mimic the amino acrylate species found usiag clavulanic acid and sulbactam. Upon the reaction of this compound with the enzyme, the potential exists for further Michael addition to inactivate the enzyme. The compound is indeed a -lactamase inhibitor but no synergy data have been reported. The related imine stmcture... 

Deuteration of C-methyl protons in simple methylpyrimidines and their amino and hydroxy derivatives has been studied under acidic and basic conditions. The exchange is acid/base catalyzed with, for example, a minimal rate at pH 4 for 1,4,6-trimethylpyrimidin-2(lH)-imine (67JCS(B)171). 

Ethoxymethylene- and aminomethylene-amino intermediates are also of use for preparation of 4-ones and 4-imines, e.g. (121) — (122) — (123) from o-aminopyridine esters (78KGS1671) and nitriles (e.g. 75JCS(P1)2182>. 

Amino Exist to a small extent only in the imine form Amide... 

In addition to (461), Dorn has described the imine (463) isolated from 5-amino-l-methylpyrazole and arenesulfonyl chloride (80CHE1). Upon heating, or in the presence of triethylamine, it undergoes rearrangement to the more stable 5-bis(arylsul-fonamido)pyrazoles (464). 5-Iminopyrazolines (461) react with acyl chlorides at the exocyclic nitrogen atom to afford amidopyrazolium salts (B-76MI40402). 

Ring expansion of haloalkyloxiranes provides a simple two-step procedure for the preparation of azetidin-3-ols (Section 5.09.2.3.2(f)) which can be extended to include 3-substituted ethers and O-esters (79CRV331 p. 341). The availability of 3-hydroxyazetidines provides access to a variety of 3-substituted azetidines, including halogeno, amino and alkylthio derivatives, by further substitution reactions (Section 5.09.2.2.4). Photolysis of phenylacylamines has also found application in the formation of azetidin-3-ols (33). Not surprisingly, few 2-0-substituted azetidines are known. The 2-methoxyazetidine (57) has been produced by an internal displacement, where the internal amide ion is generated by nucleophilic addition to an imine. 

Peptide synthesis via a three or tour component condensation (amino acid, imine and bocyanide)... 

Aminosalicylic acid (5-amino-2-hydroxybenzoic acid) [89-57-6] M 153.1, m 276-280 , 283 (dec), pK 2.74 (CO2H), pK 5.84 (NH2). Cryst as needles from H2O containing a little NaHS03 to avoid aerial oxidation to the quinone-imine. The Me ester gives needles from C6H6, m 96°, and the hydrazide has m 180-182° (From H2O). [Fallab et al. Helv Chim Acta 34 26 1951, Shavel J Amer Pharm Assoc 42 402 1953.]... 

As with simple imines, the identity of the rate-limiting step changes with solution pH.. s the pH decreases, the rate of the addition decreases because protonation of the amino compound reduces the concentration of the nucleophilic unprotonated form. Thus, whereas the dehydration step is normalfy rate-determining in neutral and basic solution, addition becomes rate-determining in acidic solutions. 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

Another type of bifunctional catalysis has been noted with a,cn-diamines in which one of the amino groups is primary and the other tertiary. These substituted diamines are from several times to as much as 100 times more reactive toward imine formation than similar monofunctional amines. This is attributed to a catalytic intramolecular proton transfer. 

Bell and Hall have incorporated an organometallic unit into a crown by using the ferrocenyl unit as part of the ring or as a third strand. The unit is incorporated either as the 1,1 -diformylferrocene or the corresponding acid. In the former case, the bis-imine is prepared and reduced to give the saturated crown (see structure 24). In the latter case, the acid is converted into its corresponding chloride and thence into the diamide by reaction with a diamine. Diborane reduction affords the saturated amino-crown. Structure 24 could be prepared by either of these methods but the dialdehyde approach was reported to be poor compared to the amide approach which afforded the product in ca. 60% yield . 

Similarly, 1-alkylpyrroles, indoles, furans, thiophenes [60], a-picoline [61], enols, malonates [76], and organometallic compounds [56, 62] react with acyl imines of trifluoropyruvates to give derivatives of a-trifluoromethyl a-amino acids... 

Hexafluoroacetone and certain perfluorinated or partially fluorinated ketones, aldehydes, and imines react with a-functionalized carboxylic acids (e.g., a-amino, a-At-methylamino [S3, 84], a-hydroxy [S5], and a-mercapto [Sd] acids) to give five-membered heterocyclic systems (equation 13). 

An example of a biologically important aldehyde is pyridoxal phosphate, which is the active form of vitamin Bg and a coenzyme for many of the reactions of a-amino acids. In these reactions the amino acid binds to the coenzyme by reacting with it to form an imine of the kind shown in the equation. Reactions then take place at the amino acid portion of the imine, modifying the amino acid. In the last step, enzyme-catalyzed hydrolysis cleaves the imine to pyridoxal and the modified amino acid. 

FIGURE 17.11 Imine formation between the aldehyde function of 11-c/s-retinal and an amino group of a protein (opsin) is involved in the chemistry of vision. The numbering scheme in retinal is specifically developed for carotenes and related compounds. 

Analogous compounds with a secondary amino group (a,j8-unsaturated secondary amines) can, in principle, exist in either the form of imines (6) or the tautomeric form of enamines (7). As they practically occur and react in the former structure, it is more convenient to use the group designation imines. ... 

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