Amino Group Transformations

A library of di- and trisubstituted 5-amino-l 77-1-benzazepine derivatives was assembled through attachment of a preformed 1-benzazepine unit to an aminomethylated polystyrene resin. The initial solution phase synthesis of the 1-benzazepine moiety was based on an intramolecular Dieckmann cyclization (type d) followed by a ketone to primary amino group transformation via reduction ( NaBH3CN) of an imine intermediate <2007JC0487>. 

The employment of non-protic electrophiles for the foregoing type of cyclizations as illustrated in Scheme 8 has the particular merit of leaving a useful point of departure for further transformations. Comparable cyclizations of 2-allyl-3-aminocyclohexenones with mercury(II) acetate are preceded by dehydrogenation to the corresponding 2-allyl-3-aminophenol as shown in Scheme 9 82TL3591). The preferred direction of cyclization depends upon the nucleophilicity of the amino group. 

FIGURE 27.5 Tyrosine is the biosynthetic precursor to a number of neurotransmitters. Each transformation is enzyme-catalyzed. Hydroxy-lation of the aromatic ring of tyrosine converts it to 3,4-dihydroxy phenylalanine (L-dopa), decarboxylation of which gives dopamine. Hy-droxylation of the benzylic carbon of dopamine converts it to norepinephrine (noradrenaline), and methy-lation of the amino group of norepinephrine yields epinephrine (adrenaline). 

It has been found that the fusion of the pyrazole with the pyrrole ring is difficult, probably for steric reasons. All attempts to cyclize 3-amino- and 5-amino-4-acetylenylpyrazole have failed. For example, upon prolonged heating of 5-amino-4-acetylenylpyrazole 68 in DMF in the presence of Cul and (or) CuC=CPh, side transformations andresinification occurred. The side processes were suppressed by acylation of the amino group and substitution of DMF by inert cyclohexane. However, 80-90% of the starting compounds was recovered after heating acylamine... 

With 1-hydroxytryptophan derivatives, similar substituent effects are observed (99H2815). In order to realize better yields of 5-substituted tryptophans, car-boxy and amino groups are transformed to ester and/or amide groups, choosing the 1-methoxy moiety as a leaving group. As a result, ( )-Ab-acetyl-5-chlorotryptophan methyl ester (219, 52%) is obtained together with 220 (7%) from ( )-218 by the reaction with aqueous HCl (Scheme 32). ( )-5-Bromo-Ab-methoxycarbonyltryptophan methylamide (222, 50%) becomes readily available... 

Amide-induced pyridine-pyrimidine transformation is also reported with 2-bromo-l, 5-naphthyridine. 2-Methyl-4-amino-l, 3,5-triazanaphtha-lene is obtained, together with its 4-amino derivative The presence of the amino group at position 4 is certainly due to a SnH amino-dehydrogenation in preformed 2-methyl-l,3,5-triazanaphthalene (63RTC997, 73RC459, 94MI1). 

The C-coordinated thiazolium complexes are the result of the proton-induced cyclization reactions (980M513). Thus, complex 1 on protonation with tetrafiuoroboric acid yields the C-coordinated thiazolium structure 2. In turn, the nitrile complex 3 under these conditions is transformed to the thiazolium cationic species 4. Protonation of the amido complex 5 with tetrafiuoroboric acid also results in a cyclization but it proceeds differently. The amino group of the CONH2 moiety is lost and BF3-framework is coordinated via the carbonyl oxygen in an overall neutral complex 6. 

Tiazofurine (142) is an antimetabolite with antineoplastic activity. It preferentially affects leukemic lymphocytes over normal cells due to selective activation by formation of its adenine dinucleotide by transformed cells. Of the syntheses available, one starts by conversion of iniidate 138 to methyl 2,5-anhydroallonothioate (139). Next, condensation with ethyl 2-amino-2-cyanoac-etate leads to the thioamide which undergoes thiol addition to the nitrile function to produce the amminothiazolecarboxyester system of 140 directly. Sodium nitrite in aqueous hypophosphorus acid eliminates the superfluous amino group via the diazonium transformation to give 141. This synthesis of tiazofurine (142) concludes by ester amide exchange in methanolic ammonia [48]. 

In subsequent studies,22 Sheehan et al. demonstrated that the action of diisopropylcarbodiimide on penicilloate 24, prepared by protection of the free primary amino group in 23 with trityl chloride (see Scheme 6b), results in the formation of the desired -lactam 25 in a very respectable yield of 67 %. In this most successful transformation, the competing azlactonization reaction is prevented by the use of a trityl group (Ph3C) to protect the C-6 amino function. Hydrogenolysis of the benzyl ester function in 25, followed by removal of the trityl protecting group with dilute aqueous HC1, furnishes 6-aminopenicillanic acid (26), a versatile intermediate for the synthesis of natural and unnatural penicillins. 

Transformation of the Nitrile Groups of PAN into Amino Groups ... 

Fourier transform infrared (FTIR) spectroscopy is the most popular method for determining the imidization process in the solid state and identifying specific substituents on the macromolecular backbone (e.g., CN, SO3H, CO, SO2).131 A method for calculating the diermal imidization extent based on FTIR data has been reported by Pride.132 Raman spectroscopy was used on the model study of PMDA-ODA condensation, and the possible formation of an inline bond by reaction of an amino group with an imide carboxyle was evidenced.133... 

Atrazine is successively transformed to 2,4,6-trihydroxy-l,3,5-triazine (Pelizzetti et al. 1990) by dealkylation of the alkylamine side chains and hydrolytic displacement of the ring chlorine and amino groups (Figure 1.3). A comparison has been made between direct photolysis and nitrate-mediated hydroxyl radical reactions (Torrents et al. 1997) the rates of the latter were much greater under the conditions of this experiment, and the major difference in the products was the absence of ring hydroxylation with loss of chloride. 

Isoxazolidines can be converted easily to tetrasubstituted cyclobuty-lamines. This transformation involves a one-pot, two-stage reaction involving hydrogenolysis of the isoxazolidine ring on Pd/C in AcOEt and the N-tert-butoxicarbonylation of the resulting amino group (Scheme 4.144).542... 

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