6,3-lactone amide

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

A closely related procedure results in formation of y-lactones. Amides are converted to AHodoamidcs by reaction with iodine and /-butyl hypochlorite. Photolysis of the AHodoamides gives lactones via iminolactone intermediates.372... 

Acids, Esters, Lactones, Amides, Imides, and Anhydrides... 

Biguanides [H2NC( = NH)NHC( = NH)NH2] react with lactones, amides, ortho esters, esters, acid anhydrides and acid chlorides to produce a wide range of 6-substituted 2,4-diamino-1,3,5-triazines (515) (59HC(l3)i). Biguanides with carbodiimides, isothiocyanates and ketones give corresponding melamines, thiones and dihydro derivatives, respectively. 

In this section the synthesis of coumalic acid (92), representing the a(2)-pyrone system, is described. a-Pyrones readily undergo a simple lactone-amide transformation, and the conversion of coumalic acid into the tautomeric 6-hydroxy-nicotinic acid (93) provides a further illustration of the conversion of a six-membered oxygen heterocycle into the corresponding nitrogen system. 

Substitution of chloride in a variety of heterocyclic chlorides by esters, lactones, amides and lactams has been shown to occur in toluene in the presence of hexam-ethyldisilazide (NaHMDS) acting as a base.52 An example using a chlorothiadiazole derivative is shown in Scheme 6. There has been a report53 of a mild and convenient method for the introduction of tetrafluoroethyl substituents into nitrogen heterocycles using the reaction of hexafluoropropane with azine and azole A-oxidcs. 

Esters are prepared by reaction of aldonic acids or lactones with an alcohol in the presence of hydrogen chloride 80 the reaction is slower with 1,4-lactones. Amides are readily formed from lactones by reaction with liquid ammonia followed by evaporation of the solvent.81 D-Gluconamide has also been prepared by treatment of D-glucono-1,5-lactone with concentrated ammonium hydroxide and subsequent precipitation with ethanol.82 A-Substituted aldonamides may be obtained by reaction of the aldono-lactones with ethanolamine, diethanolamine, and related species.83... 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

Hydrolysis Oxidation Photolysis Esters, lactones, amides, lactams, oximes, imides, and malonic ureas Amines, sulfides, disulfides, sulfoxides, phenol anions, thiols, nitriles, and catechols Aromatic hydrocarbons, aromatic heterocyclics, aldehydes, and ketones... 

Lithium aluminium hydride is highly reactive and can also reduce carboxylic acids, acid chlorides, anhydrides, esters, lactones, amides, lactams, imines, nitriles and nitro group. For example, -COCI, -CO2H, -C02Et, -CHO and >CO are reduced to -CH2OH or >CHOH, provided the correct solvent is used. 

Under these conditions esters, carboxylic acids, lactones, amides, nitriles, alkyl halides, and nilro compounds arc not reduced. Some of the groups are reduced, however, in refluxing 2-cthyHiexanol (I30 ). 

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. 

Methylenation of carbonyl groups from aldehydes, ketones, esters, lactones, amides by Ti reagents (see 1 st edition). 

It is claimed that styrene/butadiene diblock polymers bring about an improvement in the hardness, strength, and processability of polybutadiene elastomers (27), as well as an improvement in the ozone resistance of neoprene rubber (28). Styrene diblock polymers have also been made with isoprene, a-methyIstyrene, methyl methacrylate, vinylpyridine, and a-olefins. Block copolymers of ethylene, propylene, and other a-olefins with each other have been made as well. Heteroatom block copolymers based on styrene or other hydrocarbons and alkylene oxides, phenylene oxides, lactones, amides, imides, sulfides, or slloxanes have been prepared. 

Reduction of a, -unsaturated carbonyl compounds. This binuclear cluster compound reduces only the C C bond of ,j8-unsaturated ketones, aldehydes, esters, lactones, amides, and nitriles. Yields are usually >90%. A possible mechanism is suggested in the communication. ... 

Functional Group Reductions General. The chemoselecti-vity available with NaBHsCN is remarkably dependent on solvent and pH. Under neutral or slightly acidic conditions (pH > 5), only iminium ions are reduced in protic and ether (e.g. THF) solvents. Most other functional groups including aldehydes, ketones, esters, lactones, amides, nitro groups, halides, and epoxides are inert under these conditions. 

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