Cyclic amides, preparation

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

Complexes of the lanthanides with a few cyclic amides are known. Miller and Madan have reported the complexes of 7-butyrolactam with lanthanide nitrates (60) and perchlorates (61). Complexes of lanthanide perchlorates and lighter lanthanide nitrates with BuL have a L M of 8 1. However, complexes of heavier lanthanide nitrates have a L M of only 3 1. By changing the solvent used for the crystallization of the abovementioned complexes, complexes of the formula [La(BuL)4(N03)3] and [Gd(BuL)3(N03)3] could be prepared (60). Complexes of NMBuL (61, 62) and CLM (63-66) have also been reported. 

Turning our attention first to alkyl carbamates of cyclic amides, we find interesting attempts to improve the pharmaceutical and pharmacokinetic properties of 5-fluorouracil (8.152, R = H) [194-196], This antitumor agent, while clinically useful, suffers from poor water solubility, unsatisfactory delivery properties and low tissue selectivity. A variety of prodrug candidates were prepared, in particular the alkyl and aryl carbamates presented in Table 8.12. With the exception of the more-lipophilic derivatives, these compounds exhibited somewhat improved water solubility. More importantly, both rectal and oral bioavailability were markedly improved. The activation... 

The five-membered cyclic amide pyrrolidone has achieved widespread attention in the area of heterocyclic polymers since the first preparation and polymerization reactions of l-vinylpyrrolidin-2-one (1) were reported in the early 1940s. Poly(vinylpyrrolidone) (2) and its copolymers are among the most thoroughly studied heterocyclic addition polymers (B-74MI11100). Monomer (1) is readily polymerized (B-77MI11100) both free radically and ionically (Scheme 1). The former method is by far the most important, and allows the preparation of a wide variety of copolymers. Interestingly, in the homopolymerization of vinylpyrrolidone (1), the molecular weight of the polymer obtained does not appear to be influenced by the initiator concentration or the reaction temperature. 

Cyano compounds liquid crystals, 12, 278 in silver(III) complexes, 2, 241 Cyanocuprates, with copper, 2, 186 Cyano derivatives, a-arylation, 1, 361 Cyanosilanes, applications, 9, 322 Cyclic acetals, and Grignard reagent reactivity, 9, 53 Cyclic alkenes, asymmetric hydrosilylation, 10, 830 Cyclic alkynes, strained, with platinum, 8, 644 Cyclic allyl boronates, preparation, 9, 196 Cyclic allylic esters, alkylation, 11, 91 Cyclic amides, ring-opening polymerization, via lanthanide catalysis, 4, 145... 

Several blue tetra- and octanuclear Pt complexes, prepared upon reaction of cis-[Pt(NH3)2(H20)2]2+ with open and cyclic amides, as well as cyclic imides and a uracil nu-cleobase, and comprised of binuclear building blocks interacting through Pt-Pt bond formation, have been isolated and structurally characterized in recent years. Without exception, the average Pt oxidation state in these compounds is 2.25. Nevertheless, the structure and mode of action as antitumor agents of the Platinum Pyrimidine Blues , as prepared by Rosenberg in the early 70 s, remain elusive. This account represents a summary of our present knowledge on cationic Platinum Blues , with a focus on those blues obtained from cis-[Pt(NH3)2(H20)2]2+ and pyrimidine nucleobases, and presents speculations on reasonable alternative structures. 

A major problem, that of reproducibility, soon became evident. Preparation of a class I blue , to which this discussion is restricted, typically involved incubation of an aqueous solution of CD -[Pt(NH3)2(H20)2](N03)2 (prepared from cisplatin and AgN03) with a pyrimidine-2,4-dione or a cyclic amide over a period of 3 - 5 days in air, 37 °C, with the pH kept constant (at 7) by repeated addition of NaOH. Various fractions of products were then obtained upon cooling the solution and/or after addition of ethanol. Consequently, these fractions differed in color (dark blue, light blue, green, purple), as did elemental analysis data. If the pH was not kept at 7 but rather allowed to drop, products were likewise different. In particular,... 

Cyclic amides can be used like the thioamides of the previous section. l-(2-Chloroethyl)imidazolidine-2-one 61 with potassium hydroxide affords the tetrahydroimidazo[2,l-A oxazole 62 (Scheme 38) <1957JA5276>. The bicyclic imidazo[2,l-A]oxazole 64 can be prepared by the cyclization of 63 (Scheme 39) <1999H1081>. A similar methodology was applied to the synthesis of oxazolo[3,2- ]benzimidazole 66 by heating 2-chloro-l-phenacylbenzimidazole 65 with sodium benzoate in DMF (Scheme 40) <2001CHE1179, CHEC-III(11.04.9.1.1)151>. 

A series of 12- to 15-membered C-substituted cycles was prepared according to Scheme 12. Amide-benzylimines 70 were reductively coupled to the cycles 71 in a moderate yields and the cyclic amides were reduced with borane to give the free amines 72 <1995JOC3980>. Similarly, some other C-substituted derivatives were obtained <1995JOC3980>. 

In principle, any compound prepared by a ring-closure reaction in Section 14.11.5.3 and substituted with a removable substituent on ring nitrogen atoms can serve as a protected cycle. This is particularly true of a full range of the cyclic amides and sulfonamides (mostly tosylamides). Examples of the approach are 172 and 173 prepared by the tosylate method from tosylated and benzylated precursors <1995T1197>. Protected 16-membered tram 1,9-dibenzyl-l,5,9,13-tetraazacyclohexadecane was also obtained in this way <1998SC285>. 

The preparation of crown ethers differs principally owing to the presence or absence of nitrogen. The preparation of all-oxygen heteromacrocycles has largely involved the Williamson ether synthesis. The preparation of aza-, diaza-, or triazacrowns has usually required the formation of cyclic amides, followed by reduction. The latter method applies to cryptands as well and has been used for that purpose since 1969. The methods are well known and shown in the lower panel of Figure 4. 

The preparative value of this reaction is limited to a few special cases. Oximes of cyclopentanone and cyclohexanone are rearranged by concentrated sulfuric acid to cyclic amides of w-amino acids (cf. method 248). 

A different synthetic strategy for the preparation of triazoles with a carboxylic acid or related functional sidechain starts from oxazolinones or thiazolinones, i.e. cyclic amides, to provide the carboxylic function. An ArNj or ArNHN= functional group is attached to the reactive position to obtain amidrazones with endocyclic amide and exocyclic hydrazide moieties. Note that in the examples, which are not intended to exhaust variations of this approach, 4-ones as well as 5-ones may be used. 

Other amido acids may be prepared via formaldehyde amidocarbonylation using dicobalt octacarbonyl in the presence of A -substituted acyclic amides or cyclic amides. Amidocarbonylation of 2-pyrrolidone and -caprolactam [22] affords N-(2-pyrrolidone)-2-acetic acid and A-(e-caprolactam)-2-acetic acid, respectively (eqs. (12) and (13)). The side products shown can be recycled and eventually converted to the desired amido acetic acids. 

In addition to step and chain polymerizations, another mode of polymerization is of importance. This is the ring-opening polymerization of cyclic monomers such as cyclic ethers, esters (lactones), amides (lactams), and siloxanes. Examples of commercially important types are given in Table 10.1. Of those listed, only the polyalkenes are composed solely of carbon chains. Those that have enjoyed the longest history of commercial exploitation are polyethers prepared from three-membered ring cyclic ethers (epoxides), polyamides from cyclic amides (lactams), and polysiloxanes from cyclic siloxanes. 

Cyclic amides have been prepared by reaction of isophthalic acid chloride with 1,2-phenylendiamine in toluene [73], Complex formation between the cyclic hexamer and CaCI3 or Ca2Cl4 could be shown by X-ray crystallography. 

Figure 12.4-11 gives a survey of the substrates accepted by the different dihy-dropyrimidinase or D-hydantoinase preparations The differences between the en-zyme preparations from mammalian and microbial sources are discussed in more detail in reference13, but D-hydantoinases or dihydropyrimidinases, respectively, seem to have the following in common (i) a wide substrate specificity, (ii) metal dependence and (iii) that they are strictly D-specific. Preferably, cyclic amides are hydrolyzed at pH values around 8.5. Furthermore, most of the enzymes are also described to be able to catalyze the hydantoin formation the optimal pH of this reaction is neutral or weakly acidic. 

The reaction between primary amines and simple ester groups to form amides has been known since the beginning of organic chemistry. The formation of cyclic amides by this process was known before crown ethers were discovered. As an example, benzodiazepinone was prepared by a cyclic amide formation reaction as shown (Archer and Sternbach, 1966). 

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