Pyridinone preparation

Mariano, P.S., Krochmal, E., Jr., and Leone, A., StQbene like photocycKzations of l-phenylvinyl-2-pyridinones. Preparation of 4H-benzo[a]quinoIizin-4-ones,/. Org. Chem., 42, 1122—1125, 1977. 

Treatment of a chiral amine with phosgene is the cheapest way to prepare symmetrical ureas [29]. Nevertheless, due to the toxicity and reactivity of that reagent, it can advantageously be replaced by triphosgene [30] or l,l -carbonyldiimidazole [31-34] or other derivatives such as l,l -carbonyldi-2(lH)-pyridinone [35]. This procedure can be extended to thiophosgene (Scheme 1) and its thio-analogues, such as l,l -thiocarbonyldi-2(lH)-pyridinone to produce thioureas [36] chiral diamines can thus be transformed into the corresponding monoureas or monothioureas. 

The fact that pyromeconic acid and allomaltol were only available with difficulty meant that direct synthesis of certain 3-hydroxy-4-pyridinones was not possible. However the demonstration that some of these compounds were accessible from maltol or ethylmaltol by functionalizing the position adjacent to the ring-oxygen by an aldol condensation and N-oxide intermediates led to the preparation of 2-(l -hydroxyalkyl) and 2-amido derivatives with usefully high affinities for Fe + (70). 

BMOV, was reported in 1972 159) and in 1987 160). Its electrochemical preparation was described in 1978 92a), and EPR monitoring of its redox behavior, in chloroform, in 1987 160). However this now-important compound seems not to have been properly characterized until 1992 161). Since then complexes of several 3-hydroxy-4-pyridinones 162—164), and of l-hydroxy-2-pyridinone 165), have been synthesized and characterized, especially by EPR 164). VO(malt)2 exists as a cis trans equilibrium mixture in aqueous solution, and generally crystallizes as a mixture of the two isomers. However the crystal structure of the trans structure was eventually solved, confirming the expected square-pyramidal stereochemistry 166). The relative stabilities of the cis and trans forms of V 0L2 complexes depend on the nature of the bidentate ligand L , with the cis configuration favored by VO(malt)2 and VO(koj)2 167), but the trans by 3-hydroxy-4-pyridinonate ligands 164). 

L — maltolate the coordination environment of the vanadium in K[V02(malt)2] H2O is approximately octahedral, the two 0x0 ligands being in cis positions. [K(H20)e] units link adjacent vanadium(V) complex anions to give a chain structure 166). The main products of aerobic oxidation of [V O(dmpp)2l in aqueous solution are [V02(dmpp)] and [VOo(dmpp)2]. High pH favors these V products, whereas at low pH V species predominate 171). Vanadium(V) also forms a VO(OR)(malt)2 series, readily prepared from ammonium vanadate, maltol, and the appropriate alcohol in a water-alcohol-dichloromethane medium 172), and 3-hydroxy-4-pyridinonate analogues V0(0R)L2 on oxidation of their oxovanadium(IV) precursors in solution in the appropriate alcohol ROH 168). 

A series of Tc complexes with the monobasic ligands 2-methyl-3-oxy-4-pyronate (maltolate, Hma (78)) or l,2-dimethyl-3-oxy-pyridinonate, (Hdpp, (79)) were prepared in nonaqueous solution by chloride substitution in [TcOCU]. Stepwise substitution is observed. The substitution of one... 

Hydroxypyridonimine analogues (177) of the much-studied 3-hydroxy-4-pyridinones (cf. Section 5.4.5.5.2), are prepared from maltose or lactose. They form stable iron(III) complexes. 

The preparation of metal complexes from hydroxypyridinones is usually simple and straightforward—the more difficult task is generally the synthesis of the required ligand. There may also be difficulties in separating complex from ligand, especially for the more lipophilic complex S sublimation, used in the case of A -n-hexyl, may be more successful than recrystallization. 3-Hydroxy-4-pyridinones are for the most part accessible from hydroxypyranones. Reagents developed for analytical and separation purposes (preparative methods may be traced back... 

Intermolecular cycloadditions involving pyridinones are well known (80H(14)1793). 4-Cyano-l-methylpyridin-2-one undergoes Diels-Alder reaction with a suitable diene (equation 195) (79H(12)l). The pyridinone (307) forms 1 1 and 1 3 adducts on reaction with DMAD under pressure (Scheme 225) (82H(19)499). 2-Azabarrelenone (308) may be prepared by a sequence (Scheme 225), the first step of which is the addition of maleic anhydride to l-benzylpyridin-2-one (80AG(E)463). 

A versatile and flexible route to naphthyridines, containing an isoquinolinic nitrogen, and their corresponding A -oxides, has been reported from various o-bromopyridinecarbaldehydes and ammonia <1999S306>. Highly functionalized naphthyridones (and quinolines) have been prepared from a common A -aryl pyridinone template (Scheme 39) <20020L2071>. 

Azine approach. Oxazolo[3,2-a]pyridinium salts (210) were first obtained from the cyclodehydration reaction of l-phenacyl-2(lii)-pyridinone in sulfuric acid (67JHC66). These salts can also be prepared from 2-halo-l-phenacylpyridinium derivatives (211) by treatment with a base which causes ylide formation and hence cyclization by intramolecular substitution (69JOC2129, 76CB3646). It is recommended that a bulky tertiary amine is used as base in order to avoid opening of the ring or substitution of the 2-halo substituent in the starting material (211). Isoquinoline and quinoline analogues have also been prepared by these methods. 

Azine approach. It is claimed that a stepwise procedure is required for the preparation of oxazolo[5,4-6]pyridines (246) from 3-amino-2(l//)-pyridinones firstly the amino group... 

Rearrangement of alkoxycarbonyl imidazole acryl azides in diphenyl ether at high temperatures afforded imidazo[l,5-c]pyrimidinone or imidazo[4,5-c]pyridinone derivatives <02TL5879>. Efficient synthesis of imidazopyridodiazepines from peri annulation in imidazo[l,2-a]pyridine has been described <02TL9119>. A convenient synthesis of 3,6-disubstituted-2-aminoimidazo[l, 2-a]pyridines has been published <02TL9051>. Novel 2,3-dihydroimidazo[2,l-h][l,3]oxazoles were prepared from intramolecular nucleophilic i/wo-substitution of 2-alkylsulfonylimidazoles <02S2691>. 4,4 -Bi-l//-imidazol-2-ones were efficiently synthesized from 5-amino-ot-imino-1 //-imidazole-4-acetonitriles and isocyanates <02JOC5546>. 

Amino-bicyclic pyrazinone, (V), and pyridinone derivatives prepared by Zhang (5) were effective as factor Vila inhibitors and as selective inhibitors of serine protease enzymes associated with the coagulation cascade. 

The use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

The sulfonylamide analogue of the current invention, 3-(3-chlorobenzylsulfonyl)amino-6-methyl-1 - [(2-guanidinooxyethyl)-aminocarbonylmethyl]-2-pyridinone trifluoroacetate, (II), has been prepared and is described (2). 

A series of hydroxypyridinone tripods has been used as metal chelators. The derivative (125) has been prepared by carboxylation of l-methyl-3-hydroxy-2(lH)-pyridinone under... 

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