Lactams, preparation from lactones

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

Macrocyclic 14-membered lactams, lactones, and thiolactones 211 have also been prepared from 3-amino-l,2,5-thiadiazole-4-carboxylic acids 210 (Equation 47) <1996CHE975>. 

Piperidones of two types have been prepared from saccharide derivatives. Those of one type are lactams, exemplified by 187, obtained by oxidizing255 5-azido-5-deoxy-2,3-0-isopropyidene-/3-D-ribo-furanose (185) to 186, reducing the lactone 186 to the amine, and cyclizing this to 187. The other type comprises the 4-piperidones such as 189 this is obtained256 by oxidizing methyl a-D-arabinopyrano-side (188) with periodate, and treating the product with methylamine and 3-oxopentanedioic acid the bicyclic compound obtained from the a-glycoside differs from that from the /3 anomer. 

The most general method of preparing 2-carbonyl derivatives is to react 3-aminopropanols with difunctional derivatives of carbonic acid.1 2-Oxo derivatives of tetrahydro-1,3-oxazine being both 8-lactams and 8-lactones differ in their chemical properties from those of tetra-hydro-1,3-oxazines. 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

Vinyloxiranes are used for facile 7i-allyl complex formation [14], The -allylic ferralactone complex 41 was prepared by oxidative addition of Fe2(CO)9 to the functionalized vinyloxirane 40 and CO insertion. Treatment of the ferralactone complex 41 with optically active a-methylbenzylamine (42) in the presence of ZnCl2 gave the 7r-allylic ferralactam complex 45 via 44. In this case, as shown by 43, the amine attacks the terminal carbon of the allylic system and then the lactone carbonyl. Then, elimination of OH group generates the 7r-allylic ferralactam complex 45. Finally the /1-lactam 46 was obtained in 64% yield by oxidative decomplexation with Ce(TV) salt. The <5-lactam 47 was a minor product (24%). The precursor of the thienamycin 48 was prepared from 46 [15,16]. This mechanistic explanation is supported by the formation of both 7r-allyllactone and lactam complexes (49 and 51) from the allylic amino alcohol 50 [17]. 

Note that the polymerizations of lactones and lactams give polyesters and polyamides, respectively, polymers that can also be synthesized by conventional step-growth polymerization from noncyclic monomers. Although the polymer prepared from cyclic monomers looks like a condensation polymery in strict terms it is not, because no small-molecule byproduct was pro-... 

Pyrrolidine (39 Z = NH) and thiolane (39 Z = S) can be prepared from tetramethylene dibromide 38, and tetrahy-drofuran (39 Z = O) is obtained from the diol 40. -Hydroxy and -thiol acids (41 Z = O, S) usually cyclize spontaneously to give lactones and thiolactones 42. -Amino acids (41 Z = NH) require heating to effect lactam formation (42 Z = NH) (Scheme 31). 

The lithium amides 98, prepared from 4-hydroxy—lactone and imines, rearranges in the presence of lithium chloride at low temperature to form -lactams 99 (Scheme 52) with cholesterol absorption inhibition properties <1999JOC3714, CHEC-III(2.01.3.10.10)69>. 

Similarly, urea TV, 0-acetal 64 undergoes condensation reaction with weak carbon acids to afford acyclic 1,1-enediamines with the elimination of alcohol and amine42,95. A number of active methyl compounds such as an aliphatic ketone, acetophenone, imino ester and thioacetoamide has been successfully converted to 1,1-enediamines. Lactones, lactams and thiolactams condense with 64 to give enediamines 65 in moderate yields (equation 24). Very weakly activated methyl groups are also reactive towards urea A, 0-acetal 64, and 1,1-enediamines 66-71 are prepared from the corresponding reactants42,95. 

Enamide 319, prepared from the lactone 318 and 3-pyrrolidinol, in several steps, was heated at 140°C to give the homogeneously cyclized lactam 320 in 51% yield this was then hydrogenated to afford 7-oxo-a-ly-corane (321) (151) (Scheme 116). 

Indium enolates, prepared conveniently by transmetalation of hfhium enolates with IriCl j, react wifh aldehydes to give fhe corresponding -hydroxy esters [80]. Ultrasound irradiation promotes fhe Reformatsky reaction of aldehydes and ethyl bromoacetate wifh indium [81]. Indium-mediated Reformatsky reaction of phenyl a-bromoalkanoates wifh ketones or aldehydes gives di-, tri-, and tetrasubstituted -lactones (Scheme 8.57) [82]. Indium-mediated reaction of imines with ethyl bromoacetate gives 3-unsubstituted -lactams (Scheme 8.58) [83]. An indium-Refor-matsky reagent prepared from 2-(chlorodifluoroacetyl)furan couples with aldehydes (Scheme 8.59) [84]. 

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. 

Provided that they have at least one hydrogen atom on the amide-nitrogen, the hydroxy carboxamides formed from lactones can be converted by heat into lactams. For example, the above o-(hydroxymethyl)-A -methylbenzamide (2) cyclizes to the lactam (3) at 160° however, the removal of water involved in the change (2) -> (3) competes with the loss of methylamine that leads back to phthalide, so that pressure is required in preparation of the lactam.786... 

Pyrrolidin-2-one, often called pyrrolidone, is the lactam of 4-aminobutyric acid. Pyrrolidone is prepared from butano-4-lactone and ammonia at 250°C. It is colourless, water-soluble, of mp 25°C and bp 250°C (decomp). Pyrrolidone is vinylated by acetylene. Poly-(A -vinylpyrrolidone) has proved useful as a plasma substitute in blood transfusion. 

Polymerization of cyclic ester amides with large rings (e.g., 11-, 13-, and 14-membered rings) has also been studied [6-8]. In addition, it is well known that random copolymers can be easily prepared from mixtures of lactones and lactams, and even several works have recently been focused on the preparation of block copolymers from these macrocycles [9-11]. 

Jt-Allyltricarbonyliron lactone complexe s are useful precursors for organic synthesis. They were first reported in 1964 [254] and have since been shown to be available from a variety of substrates [255]. For example, they may be prepared from alkenyl epoxides or various butenediols [256] and their derivatives by treatment with tetracarbonyl iron [257]. Work in our laboratories had shown that these were useful precursors for a wid5.,range of naturally occurring p and 5-lactones and lactams [258] (Scheme 123). 

Tricarbonyliron lactone complexes have also been used as precursors for /3-lactam preparation. Reaction of the complex (9), which is readily available from butadiene, with a protected amino-acid leads to a new lactam complex, which on oxidation gives a /3-lactam related to the nocardicins (Scheme 29). ... 

Azetidines.—ay-Dibromoesters, which are prepared from y-lactones react with amines to give azetidine carboxylic esters. Oxygenation of the dianions produced from the latter then leads to 2-azetidinones (jS-lactams) by an oxidative decarboxylation described earlier by the same group of authors (Scheme 55). 

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