Amines => lactams

Early infrared (IR) spectroscopy studies were inconclusive some37 38 were considered to indicate that cytosine exists in the amine-lactim form (1) in the solid state, others39-41 that it exists in the amine-lactam form (2 or 3). More recent studies42-50 (for reviews, see refs. 51, 52) on cytidine, 5-halodeoxycytidines, sodium cytidylate, and polycytidylic acid in neutral H20 or D20 solution advocate, however, the structure 2 for the cytosine residue. 

Table VI collects the theoretical quantities appropriate to the description of the tautomeric stability of cytosine, computed by methods including both -n- and cr-electrons. We have added to it the results of a 77-SCF MO approach (including cr-polarization effects) on heats of atomization of different tautomeric forms of cytosine. Bodor et al.liB have related the heat of atomization to the stability of the tautomers, and found that the most stable structure of the molecule is the amine-lactam 2 having the greatest heat of atomization (59.707 eV). They predict on this basis the following order of stability 2 > 3 > 6 > 1.

The X-ray crystallographic studies show that thiouracils and 2-thiocytosine exists in the crystalline state in forms 51 and 52, respectively, and that isocytosine exists as a mixture of two amine-lactam forms, 42 and 43. Several experimental studies on these pyrimidines in solution confirm the conclusions from the crystal. However, studies on the tautomerism of the minor pyrimidine bases are few. In a number of cases the conclusions about the dominant structures are intuitive rather than proved. We present the essential experimental data on the structure of the minor pyrimidine bases. 

IR studies38,40,510 suggested that this molecule exists in the solid state as well as in solution in the amine-lactam form 42 and 43, or as a mixture of the two forms. These studies were not able to distinguish... 

Using the phthalimide/methylthioether-pair, a variety of photochemical transformations resulting in medium- and macrocyclic sulfur containing amines, lactams, lactones, and crownether analogues, respectively, with a maximum ring-size of 38 atoms have been described [26,27]. Scheme 10 summarizes some selected examples. 

Amines lactams. Simple acyloxyboranes are known to react with amines to form amides, but in low yield. This reaction has been improved by use of catecholborane (equation I). It can be extended to synthesis of lactams. Thus addition of catecholborane to a suspension of an w-amino acid in pyridine (80°) results in a lactam. Yields are high (85-95%) for 3- and 5-membered lactams. Yields are low (—6 (.) in the case of medium-size lactams, but improve to 10-15% in the synthesis of 14- and 16-mcmbcrcd lactams. (Dimers are formed preferentially.) Yields are... 

Shi Q, Chen K, Brossi A, Verdier-Pinard P, Hamel E, McPhail AT, Lee KH. Antitumor agents 184. Syntheses and antitubulin activity of compounds derived from reaction of thiocolchicone with amines lactams, alcohols, and esters analogs of allothio-colchicinoids. Helv. Chim. Acta 1998 81 1023-1037. 

Diphenylphosphinoyl)hydroxylamine (Eq. 137),143 azo esters (Eq. 138),460 and arenesulfonyl azides (Eq. 139)339 have been used to aminate lactam enolates. In the azidation of the lactam 70,461 the diazo compound 73 predominates over azide 72 even though trisyl azide is used as the animating agent amination with di(ferf-butyl) azodicarboxylate was unsuccessful. The closely related lactam 71462 reacts normally with trisyl azide (Eq. 140). 

Thus, we first discuss thermodynamics, paying attention to features that are important for polymer synthesis (e.g., dependence of equilibrium monomer concentration on polymerization variables) then we describe kinetics and thermodynamics of macrocyclization, trying to combine these two related problems, usually discussed separately. In particular we present the new theory of kinetic enhancement and kinetic reduction in macrocyclics. Thereafter, we describe the polymerization of several groups of monomers, namely cyclic ethers (oxiranes, oxetanes, oxolanes, acetals, and bicyclic compounds) lactones, cyclic sulfides, cyclic amines, lactams, cyclic iminoethers, siloxanes, and cyclic phosphorus-containing compounds, in this order. We attempted to treat the chapters uniformly we discuss practical methods of synthesis of the corresponding polymers (monomer syntheses and polymer properties are added), and conditions of reaching systems state and reasons of deviations. However, for various groups of monomers the quality of the available information differ so much, that this attempt of uniformity can not be fulfilled. 

The Painter group developed another approach to tetramates (e.g., 320) that involved the reductive amination of y-oxobutenoates (e.g., 319) in the presence of primary amines (Scheme 81 2002S869). Unsaturated dicarbonyl 319 was prepared in three steps by the phosphine-catalyzed Michael addition of benzyl alcohol to butynoate 318, desilylation, and oxidation of the resulting primary alcohol with 2-iodoxybenzoic acid (IBX). Treatment of 319 with tert-butylamine followed by sodium borohydride gives the O-benzyl tetramate 320 via a reductive amination—lactamization. 

Amination-lactamization cascade for the preparation of valuable lactams, (a) 6-Methyl-piperidin-2-one, (b) 4-phenylpyr-rolidin-2-one, and (c) synthesis of niraparib precursor. 

---