Imidazole-2,4 -diones

Imidazole-4,5-dicarboxylic acids, coupling, 5, 403 decarboxylation, 5, 434 1-substituted synthesis, 5, 468 synthesis, 5, 362, 402, 484 Imidazole-4,5-dione, l-alkyl-2-phenyl-synthesis, 5, 129, 479 Imidazole-2,4-diones tautomerism, 5, 370 Imidazole-4,5-diones tautomerism, 5, 370 Imidazole-2,4-dithione, 5,5-diphenyl-tautomerism, 5, 370 Imidazole-2,4-dithiones tautomerism, 5, 370 Imidazolepropanol synthesis, 5, 486 Imidazoles accelerators epoxy resins, 1, 407... 

Coyle. J. D. and Bryant. L. R. B., niotochem-ical cyclizalion of 3-N-(dialkylaminome-thyl)imidazole-2,4-diones to 1,3,7-triazabi-cyclol.3.3.01oclancs, J. Chem. Soc. Perkin Trams. /. 531. 1983. 

Figure 12-18. Chemical relationships of antiepileptic drugs. ° The keto between nitrogens is reduced to CH2.b Imidazole-2,4,-diones.c Formerly diphenylhydantoin.d Double bond.e The 10-11 epoxide is an active metabolite.

Hydantoins essentially have the imidazole-2,4-diones moiety. 

Because free or esterified imidazole(4,5)-acetates 745 are currently accessible only via a rather tedious multistep synthesis via (4,5)hydroxymethylimidazole [224— 226], it seemed obvious to react amidines such as isobutyraminidine-HCl 742 with commercially available methyl or ethyl 4-chloroacetoacetates 743a, b to obtain 745 directly in one step. Because of the low reactivity of the 4-chlorine in 743, however, reaction of 743, e.g. with isobutyramidine-HCl 742 in the presence of sodium methylate in methanol, affords exclusively 2-isopropyl-6-chloromethyl-pyri-midin-4-one 744 [227], whereas treatment of 743b with NaOEt in EtOH gives, in the absence of amidines, 2,5-bis(ethoxycarbonyl)cyclohexane-l,4-dione in nearly quantitative yield [228, 229]. 

As compounds exhibiting enhancing effects on CL reactions, a variety of phenols, e.g., firefly luciferin and 6-hydroxybenzothiazole derivatives [12,13], 4-iodophe-nol [14], 4-(4-hydroxyphenyl)thiazole [15], 2-(4,-hydroxy-3 -methoxy-benzyli-dene)-4-cyclopentene-l,3-dione (KIH-201) [16], and 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDI) and 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole (HPI)[17] (Fig. 6A), and phenylboronic acid derivatives, e.g., 4-phenylylboronic acid [18], 4-iodophenylboronic acid [19], and4-[4,5-di(2-pyridyl)-l //-imidazol-2-yl]phenylboronic acid (DPPA) [20] (Fig. 6B), in the luminol/hydrogen peroxide/peroxidase system are well known. Rhodamine B and quinine are used as sensitizers in the CL-emitting reaction between cerium (IV) and thiol compounds. This CL reaction was successfully applied to the sensitive determination of various thiol drugs [21-32],... 

Figure 6 Representative (A) phenol-type and (B) phenylboronic acid-type enhancers for luminol/hydrogen peroxide/peroxidase system. KIH-201, 2-(4 -hydroxy-3 -methoxy-benzylidene)-4-cyclopentene-1,3-dione HDI, 2-(4-hydroxyphenyl)-4,5-diphenylimida-zole HPI, 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole DPPA, 4-[4,5-di(2-pyridyl)-lH-imidazol-2-yl]phenylboronic acid).

Sequential condensations with 2-bromo-2-bromomethylcyclopropane-l-carboxylate and an imidazole derivative, and then guanidine gave the novel ring-expanded 108 with a 6H-imidazo[4,5-e][l,3]diazepine-4,8-dione skeleton <00JHC951>. Another 6-amino-2-phenyl derivative of this ring system has also been reported . 

Some structures, related to pyrrolo[l,2- ]imidazoles, have been reported. The tricyclic perhydro derivative 49 <1997TL1647> as well as the 3-( 1 //-indol-3-ylmethy 1 )-7a-methyldihydro-1-phenylamino-l//-pyrrolo[ 1,2-tf] imidazole-2,5(3//,6//) dione 50 have been determined and some interesting aspects on compound 50 have been highlighted. 

Table 1 Preparation of various dihydro-1 H-pyrrolo[1,2-a]imidazole-2,5-diones...

Nucleophilic attack of substituted alkylamines including benzylamines to 6,7-dihydro-imidazo[l,2- ]imidazole-2,5-diones 34, cleaved the imidazolidinone ring to generate the acetamide derivatives 81 (Equation 34) <1998APH389, 2001JST73>. Reaction of the tricyclic thiazolium salt 45 with methoxylamine gave the oxime 82 (Equation 35) <1999JME2828>. 

More recently, a new and straightforward one-pot approach was reported by Bu et al. <2003JOC5415>. This reaction involves the cyclocondensation of l,2-dipyridin-2-yl-ethane-l,2-dione 120 and arylaldehydes, in the presence of ammonium acetate. Imidazo[l,5- ]pyridines 121 were obtained in reasonable yields, but competitive formation of imidazoles 122 was observed. The amount of ammonium acetate used in this reaction was also shown to strongly influence the yield of the cyclization (Scheme 38). 

The above diketones are also convenient and versatile starting compounds for the synthesis of photochromes containing heterocyclic bridges. Thus, ethane-l,2-dione 223 with aldehydes and ammonium acetate in acetic acid gave imidazoles 271 (Scheme 75) (05ZOR1375). 

Early claims to have prepared 4-hydroxy-4H-imidazoles from benzami-dine hydrochloride (27) and 2,3-butanedione (28), or phenylethane-1,2-dione (29), appear to be substantially correct (Scheme 9). Although this work has not been repeated, analogous intermediates have been observed subsequently in related reactions. Waugh and co-workers recognized that 30 might well have been the rearranged isomer 31. (see Section IV,A,l,b). 

New examples involve the reaction of 5-vinyl-17/-imidazole 293 with 4-phenyl-l,2,4-triazoline-3,5-dione 294. In this way, the imidazo[4,5-i ]pyridazine skeleton was smoothly constructed (Equation 72) <1998TL4561>. Another example using in situ formed 294 can be found in Section 8.01.6.5. 

The first member of the diazaphenalene system (which could be considered to be a benzonaphthyridine) to be synthesized was the 1,6-diazaphenalene (353). This was obtained in six steps starting from the reaction of dimethyl acetonedicarboxylate with cyclohexane-1, 3-dione. The intermediate steps are shown (78H(9)1561, 79H(12)903>. Compound (353) has similar chemical and physical properties to those of imidazole. For a full account of the syntheses and reactions of this ring system the review <83H(20>87) should be consulted. 

Glycoluril or Glyoxaldiureide, called in CA Tetrahydro-imidazo[4, d] imidazole-2,5(lH,3H)-dione. See ACETYLENEDIUREIN AND DERIVATIVES in Vol 1, p A65... 

Heating 4,5-dihydroxy-2-imidazolidinone with urea under acidic conditions yields tetrahydroimidazo[4,5-d]imidazole-2,5-diones(glycolurils) [68] (Eq. 51). (See Table VIII.)... 

Transsilylation. Several reagents have been recommended for preparation of /-butyldimethylsilyl ethers by transsilylation. These include allyl-r-butyldimethyl-silane and /-butyldimethylsilyl enol ethers of pentane-2,4-dione and methyl aceto-ucelate,2 both prepared with r-butyldimethylchlorosilane and imidazole. Unlike the reaction of r-butyldimethylchlorosilane with alcohols, which requires a base catalyst, these new reagents convert alcohols to silyl ethers under slightly acidic conditions (TsOH) in good yield. The trimethylsilyl ethers of pentane-2,4-dione and methyl acetoacetate convert alcohols to trimethylsilyl ethers at room temperature even with no catalyst. The former reagent is also useful for silylation of nucleotides.3... 

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