Carbon dioxide heterocyclics

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

A new heterocyclic system, 3 ,4-dihydro-3//-benzo[4,5]imidazo[l,2-f]oxazol-l-one 462, was synthesized by reaction of 4,4-dimethyl-5-methylene-l,3-dioxolan-2-one with o-phenylenediamine in the presence of copper bromide as catalyst in carbone dioxide at 60-80 °C under high pressure (Equation 217) <1999CHC216>. 

The formation of a double bond during anodic oxidations can result from eliminations of protons, carbon dioxide or acylium cations. The electrooxi dative aromatization of dihydropyridine derivatives and heterocycles containing nitrogen atom (di-hydroquinoxalines, tetrahydrocinnolines) involves an ECE mechanism as previously... 

Example Even a moderate voltage drop between nozzle and skimmer can cause the elimination of weakly bonded substituents such as CO2 in case of carbon dioxide-protected deprotonated A-heterocycles. In particular SnMes-substituted anions such as 2-(trismethylstannyl)pyrrole-A-carbamate exhibit variations in the [A-C02]7A ratio of up to a factor of 30 (Eig. 11.10). [76]... 

In laboratory-scale homogeneous catalysis applications, in the last decade further investigations have been carried out in which a less soluble organo-metallic catalyst system was utilized for metathesis reactions [46]. Under RCM-conditions, it was possible to convert substrates with functional groups that were problematic due to their potential to inactivate the rutheniiun catalyst here, the conversion in supercritical carbon dioxide avoids the protection of critical amino groups as an additional synthetic step. Consequently, it was possible to synthesize a number of carbo- and heterocyclic products with varying ring size (C4 to Cie). 

The reductive ring opening of six-membered nitrogen-containing heterocycles was studied with A-phenyltetrahydroisoquinoline (391). Its lithiation with lithium and a catalytic amount of DTBB (4.5%) afforded the benzylic intermediate 392, which was allowed to react with electrophiles giving, after hydrolysis, functionalized amines 393 (Scheme 110) . It is noteworthy that in the reaction with carbon dioxide, instead of the corresponding lactam, amino acid 393 with X = CO2H was exclusively isolated. 

The carbon dioxide/DBU procedure has been used synthetically for the synthesis of 5-heterocyclic substituted 2,4-quinazolinediones 820, although in this case it was necessary to operate at a much higher pressures than for the standard method <2006H(67)489>. 

Phosphites and 2,2-bis(trifluoromethyl)-5(2//)-oxazolone 71 react with elimination of carbon dioxide to give 2-aza-4-phospha-l,l-bis(trifluoromethyl)-l,3-butadiene 72 that can be used as a synthon for the previously unknown hydrogen-substituted nitrile ylide 72a in [3 + 2]-cycloaddition reactions. Examples of cycloadditions of 72a with dipolarophiles to give heterocyclic compounds 12t-ll are shown in Scheme 7.18. 

Mesoionic oxazolones (munchnones) 297 can be generated by cyclodehydration of N-substituted a-amino acids 295 or by alkylation of oxazolones 296 (Scheme 7.98). These compounds are reactive and versatile 1,3-dipoles that undergo cycloaddition reactions with dipolarophiles to generate a variety of heterocyclic systems. In particular, this is an extremely versatile methodology to prepare pyrroles that result from elimination of carbon dioxide from the initial cycloadduct. Numerous examples have appeared in the literature in recent years and several have been selected for discussion. The reader should consult Part A, Chapter 4 for an extensive discussion and additional examples. 

The most important reactions of alkyl substituents a and y to the ring heteroatom are those which proceed via base-catalyzed deprotonation. Treatment of 2- and 4-alkyl heterocycles with strong bases such as sodamide and liquid ammonia, alkyllithiums, LDA, etc., results in an essentially quantitative deprotonation and formation of the corresponding carbanions. These then react normally with a wide range of electrophiles such as alkyl halides and tosylates, acyl halides, carbon dioxide, aldehydes, ketones, formal-dehyde/dimethylamine, etc., to give the expected condensation products. Typical examples of these transformations are shown in Scheme 17. Deprotonation of alkyl groups by the use of either aqueous or alcoholic bases can also be readily demonstrated by NMR spectroscopy, and while the amount of deprotonation under these conditions is normally very small, under the appropriate conditions condensations with electrophiles proceed normally (Scheme 18). 

This chapter covers the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions from 1993 to early 2005. In addition, technical development in carbonylation processes with the use of microwave irradiation as well as new reaction media such as supercritical carbon dioxide and ionic liquids are also discussed. These carbonylation reactions provide efficient and powerful methods for the syntheses of a variety of carbonyl compounds, amino acids, heterocycles, and carbocycles. 

The apparently quite broad structural requirements for anticonvulsant activity, noted earlier in this chapter, extend to yet another class of five-membered heterocycles that include an imide function. Imidazo-2,4-diones, better known as hydan-toins, have comprised some of the most widely used drugs for treating severe motor and psychomotor epileptic seizures. The general reaction used to prepare this heterocyclic system involves the treatment of a carbonyl compound with ammonium carbonate and potassium cyanide. The first step in the complex sequence can be visualized as the addition of the elements of ammonia and hydrogen cyanide to give an a-aminonitrile (88-2). Addition of ammonia to the cyano group would then lead to an amidine (88-3). Carbon dioxide or carbonate ion present in the reaction... 

Phenyl ethylenesulfonate, 241 Tin(IV) chloride, 300 Containing one sulfur 2,4-Bis(4-me thoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide, 38 Titanium(IV) chloride-Zinc, 310 Other five-membered heterocycles Carbon dioxide, 65 Methanesulfonyl chloride, 176 Six-membered rings Containing one nitrogen—piperidines Dichlorotris(triphenylphosphine)-ruthenium(II), 107 Mercury(II) trifluoroacetate, 175 Tetrakis(triphenylphosphine)-palladium(O), 289... 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

Synthesis of the dibenzofuran (27) by irradiation of grisa-3, 5 -diene-2, 3 -dione (28) is believed to involve electrocyclic ring opening followed by intramolecular cycloaddition to the ketene and elimination of carbon dioxide, as shown in Scheme 2.24 Analogous photocyclizations are responsible for the photochromism exhibited by heterocyclic fulgides such as ( )-a-3-furyl-ethy idene(isopropylidene)succinic anhydride (29), which on irradiation... 

Carboxylate esters readily undergo photodecomposition with loss of carbon dioxide. Not surprisingly, lactones and related oxygen heterocycles undergo related transformations. A wide variety of lactones behave in this fashion443 for example, the cyclic dilactone (505) is converted on irradiation to the [2.2]paracyclophane (506).444 Of particular interest is the use of the /(-lactone (507) as a precursor of matrix-isolated cyclobutadiene (508).445... 

Barry JJA, Nazhat SN, Rose FRAJ, Hainsworth AH, Scotchford CA, Howdle SM (2005) Supercritical carbon dioxide foaming of elastomer/heterocyclic methacrylate blends as scaffolds for tissue engineering. J Mater Chem 15 4881—4888... 

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