Amide cyclic

Lactams are cyclic amides and are analogous to lactones which are cyclic esters Most lactams are known by their common names as the examples shown illustrate... 

Lactam (Section 20 15) A cyclic amide Lactone (Section 19 15) A cyclic ester Lactose (Section 25 14) Milk sugar a disacchande formed by a p glycosidic linkage between C 4 of glucose and C 1 of galactose... 

The Beckmann rearrangement of oximes of the thiophene series has been applied (besides the preparation of 2-acetamidothiophene ) to thiophenocycloalkenones (192) which gave the cyclic amide (193) hydrolyzable to the amine (194). The Beckmann rearrangement was... 

The whole concept of direct methylation has recently been critically reviewed and rejected by Gompper as a method to study tautomerism. The difference in the proportions of the two methyl derivatives produced w hen diazomethane is in excess, or the reverse, has now been ascribed to the relative importance of the Sn and Sn reactions of the tautomeric compound with diazomethane. The proportions of N- and 0-methyl derivatives formed by the reaction of cyclic amides with diazomethane has been related to the infrared vC—O frequencies. ... 

Heterocyclic compounds carrying potential hydroxyl groups are cyclic amides or vinylogs of amides. There is much physical evidence that acyclic amides exist almost entirely in the oxo form (for references see reference 6), and the apparent contradiction that ultraviolet spectral data appeared to favor the imidol formulation has now been explained on steric grounds. The value of pKr is estimated to be about 7 on the basis of pK measurements for acyclic amides. Extensive evidence, summarized in the following sections, shows that for a- and y-hydroxy heterocyclic compounds, the cyclic amide form usually predominates by a substantial factor, often ca. 10 . 

Quinoxalin-2-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

The reaction is effective with both acyclic and cyclic amides., or lactams, and is a good method for preparing cyclic amines. 

P-Lactamases (EC 3.5.2.6) produced by bacteria cleave the P-lactam ring and are responsible for their resistance to P-lactam antibiotics. Lactamases are useful catalysts for the enantioselective hydrolysis of P-lactams and other cyclic amides. P-lactams shown in Figure 6.40 were resolved by whole-cell systems containing an amidase [106]. 

Both 2-hydroxy- and 3-hydroxypyridine are hydroxylated to 2,5-dihydroxypyridine by strains of Achromobacter sp. (Houghton and Cain 1972). These metabolites are probably, however, formed by different reactions whereas 3-hydroxypyridine behaves as a true pyridine, addition of H2O across the Cg Nj bond would produce the 2,5-dihydroxy compound 2-hydroxypyridine is a cyclic amide and hydroxylation apparently occurs at the diagonal position. The degradation of 4-hydroxypyridine is also initiated by hydroxylation and is followed by dioxygenation before ring fission (Figure 10.12) (Watson et al. 1974). 

It has been found that a number of bidentate ligands greatly expand the scope of copper catalysis. Copper(I) iodide used in conjunction with a chelating diamine is a good catalyst for amidation of aryl bromides. Of several diamines that were examined, rra s-yV,yV -dimethylcyclohexane-l,2-diamine was among the best. These conditions are applicable to aryl bromides and iodides with either ERG or EWG substituents, as well as to relatively hindered halides. The nucleophiles that are reactive under these conditions include acyclic and cyclic amides.149... 

The stereochemical use of the Beckmann rearrangement in assigning configuration to ketoximes has already been referred to, and it also has a large-scale application in the synthesis of the textile polymer Nylon-6 from cyclohexanone oxime (78) via the cyclic amide (lactam, 79) ... 

PVCL is one of several nonionic water-soluble polymers that undergo heat-induced phase separation in water (Fig. 13). It has a repeating unit consisting of a cyclic amide, where the amide nitrogen is connected directly to the hydrophobic polymer backbone. 

With the Mo-catalyzed macrolactamization secured, we turned our attention to the problem of C2-C6 remote stereochemical control. Catalytic hydrogenation of unsaturated cyclic amide 76, in the presence of 10% Pd(C), resulted in the formation of 78 in 84% yield and with >98% diastereoselectivity. 

Lactams Lactams represent a special type of C=N system due to the tautomerization between the lactam (keto amine) and lactim (hydroxyimine) forms. The lactim form is much more favored for cyclic than for non-cyclic amides of carbocyclic acids. In the reaction of complex 2b with N-methyl-e-caprolactam, a simple ligand exchange reaction occurs and complex 87 can be isolated. With P-propiolactam, the alkenyl-amido complex 88 is formed, which indicates an agostic interaction. The reaction of complex 1 with e-caprolactam gives, after elimination of the alkyne and of molecular hydrogen, complex 89 with a deproto-nated lactam in a r]2-amidate bonding fashion [47]. 

Significant developments in this area have been reported by Overman as well As illustrated in Scheme 5, a Pd-catalyzed asymmetric Heck reaction leads to the formation of cyclic amide 24 subsequent treatment with aqueous acid delivers 29 in 84 % yield and 93 % ee151 Optically pure 25 is obtined after recrystallization (80% recovery). Follow-up functionalization, shown in Scheme 5, affords either physostigmine 26 or physovenine 27 It is difficult to imagine an alternative, and nearly efficient or selective, approach to the construction of these target molcules. 

In addition to its utility in the enantioselective formation of C-0 bonds (cf. Scheme 15), Trost s chiral ligand 102 has been used in the catalytic asymmetric synthesis of C-N bonds. An impressive application of this protocol is in the enantioselective total synthesis of pancrastatin by Trost (Scheme 17) H9i Thus, Pd-catalyzed desymmetrization of 112 leads to the formation of 113 efficiently and in > 95 % ee. The follow-up use of the N3 group to fabricate the requisite cyclic amide via isocyanate 117 demonstrates the impressive versatility of this asymmetric technology. 

This area has received much less attention in the literature than the reactivity of conjugated systems. As noted in CHEC-II(1996) <1996CHEC-II(8)345>, most of the examples studied contain one or two oxo groups in the six-membered ring and are cyclic amide tautomers of the corresponding hydroxyl compounds. 

Treatment of the cyclic amide 157 or the dihydro compound 159 with Lawesson s reagent gives the corresponding thioamides 158 and 160 (Equation 20) <1999JME1661>. Methylation of the cyclic amide 161 with diazomethane gives a mixture of 0,0- and TV,O-dimethyl products 162 and 163 in a ratio of 7 6 (Equation 21) <1996EJM651>. 

In systems with two oxo moieties, electrophilic attack occurs at the nitrogen of the cyclic amide. As an illustration, triazidiridine dione 32 was converted in good yield to the salt 16 upon treatment with Mel and followed by ion exchange (Equation 4) <2005H(65)1629>. Similar reactivity was observed with substrate 33, but in this case a 3/1 mixture of O-acylated and iV-acylated products 34 and 35 was obtained (Equation 5) <1997J(P1)2223>. 

In the case of a [l,2,3]triazolol,5- ]quinazolone derivative (closely related to 489) a direct one-step amination has been reported where the cyclic amide moiety is replaced by an amino substituted structural unit <2006OL2425>. 

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