1,1 -Carbonyl-diimidazole

In most cases, the proteia is immobilized onto y-aminopropyl sUica and covalently attached usiag a cross-linking reagent such as -carbonyl diimidazole. The tertiary stmcture or three dimensional organization of proteias are thought to be important for their activity and chiral recognition. Therefore, mobile phase conditions that cause proteia "deaaturatioa" or loss of tertiary stmcture must be avoided. 

The synthesis of the unsymmetrical imidazolium salt 11 bearing a planar-chiral ferrocene was described by Bolm starting from (Rp)-[2-(trimethysilyl)-ferrocenyl] methanol 12 which afforded the salt in good yield after reaction with Ar,M-carbonyl diimidazole and methylation (Scheme 9) [18]. 

A one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from acids and acyl hydrazides has recently been reported. The method involves an activation of an acid with carbonyl diimidazole followed by the addition of benzoyl hydrazide and then the addition of CBr4 and Ph3P. Under the conditions, the dehydration proceeds smoothly to provide the desired oxadiazoles in high yields <2006TL4827>. 

Procedures for the preparation of several compounds of considerable utility are described. These include 1,1 -carbonyl-diimidazole, which has been used in the preparation of esters, amides, and anhydrides, the hydrochloride and methiodide of l-ethyl-3-(3-dimethylamino)-propylcarbodiimide, which can be used for similar purposes and are especially useful in the preparation of peptides, and (+)- and (— )-< -(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid (TAPA), which is used for the resolution of polycyclic aromatic compounds. 

A somewhat different approach was presented by Rannard and Davis where they first reacted bis-MPA with carbonyl diimidazole, allowing a highly selective base-catalyzed reaction to form a hyperbranched polyester. The resulting polymers were hydroxy-functional and reported to be water-soluble [84]. 

Cyanogen bromide method A,A -Carbonyl diimidazole method Divinylsulfone method Epoxy (bisoxirane) method Ethyldimethylaminopropyl carbodiimide method Eluoromethylpyridinium toluenesulfonate method A-hydroxysuccinimide ester method Schiff base (reductive amination) method Tresyl chloride/tosyl chloride method Sulfhydryls Azalactone method (for azalactone supports)... 

An alternative [5+1] cyclization process in which, formally, an iV-(4-pyrimidinyl)amidine reacts with carbonyl-diimidazole (GDI) to form a second pyrimidine ring, has been described also (Scheme 52) <1994JHC81>. 

The quinazolinone moiety (36-3) for the cardiotonic agent prindoxan (36-5) is formed by reaction of diamine (36-1) with carbonyl diimidazole (36-2). Friedel-Crafts acylation of the product with the half-acid chloride from methyl succinate gives the corresponding keto-ester (36-4). The pyridazinone (36-5) is then obtained by condensation of that product with hydrazine [38]. 

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

Inhibitors of the blood clotting factor thrombin would in principle prove useful in preventing inappropriate clot formation that potentially leads to stroke and heart attack. Reaction of the carboxylic acid (56-2) with thionyl chloride leads to the corresponding acid chloride (56-3). Treatment of that intermediate with the substituted pyridyl amine (56-1) leads to the amide (56-4). Catalytic hydrogenation of (56-4) reduces the nitro group to the primary amine (56-5). Condensation of that ortho-diamine with the carboxyhc acid (56-6) in the presence of carbonyl diimidazole... 

A quinazolodione provides the nucleus for yet another eompound that inhibits aldose reductase. The sequence for the preparation of this agent starts with the isatoate acid (90-1) from 4-chloroantharanilic acid. Heating the compound with the substituted benzylamine (90-2) results in the formation of the ring-opened amide (90-3) with a loss of carbon dioxide. The ring is then reclosed, this time by reaction with carbonyl diimidazole, to afford the quinolodione (90-4). The anion from the reaction of this last intermediate with sodium hydride is then alkylated with ethyl bromoacetate. Saponification of the ester completes the preparation of zenarestat (90-5) [100]. 

Matsuda, Akutsu, et al. [141] carried out chemical fixation of GRGDSP onto a poly(vinyl alcohol) film which had been activated by carbonyl diimidazol in dimethylformamide. For comparison, fibronectin was also immobilized on a poly(vinyl alcohol) film by the same technique. Matsuda et al. found that bovine endothelial cells (ECs) adhered well to the peptide- and fibronectin-immobilized film furthermore, after a three-day incubation, aggregated ECs floated on nontreated PVA film, while the peptide-immobilized surface greatly enhanced cell spreading and growth, which surpassed that on fibronectin-bound PVA. 

Immunoaffinity chromatography cleanup has also been applied as an ideal and reliable strategy for residue analysis. Immunoaffinity columns prepared by coupling the antibodies to a cyanogen bromide-activated support were used to analyze avermectin BI residues in cattle tissues (359) and ivermectin in sheep serum (376). An immunoaffinity column prepared by an alternative activation/ coupling procedure with carbonyl diimidazole was also employed to analyze ivermectin residues in swine liver (361) since the earlier-reported methods did not work well in the analysis of this matrix. This recent work demonstrated the high specificity of tire antibody-mediated cleanup, but also showed that the immunoaffinity procedures could not always or completely eliminate matrix interference of samples. Therefore, application of additional cleanup steps before or after these procedures is often inevitable. 

When 2-carboxyquinoxaline 1,4-dioxide is treated with NH3 in anhydrous dimethylformamide (DMF), in the presence of (V,jV -carbonyl diimidazole, 2-carbamoylquinoxaline 1,4-dioxide is obtained.198... 

Many other means of preparation of adsorbents for affinity chromatography are also available.121122 For example, l,l -carbonyl-diimidazole can be used to couple a diamine to the matrix (Fig. 3-11). This reagent has the advantage that it does not depend upon the relatively unstable isourea linkages formed by Eq. 3-9 to hold the specific affinity ligands.121... 

Carbon monoxide oxidase 893 Carbonic acid, pkCa value of 99 Carbonic anhydrase 443,676 - 678,710 active site structure 679 mechanism 678 turnover number of 458,678 Carbonium ion. See Carbocation 1,1 -Carbonyl-diimidazole 105s Carbonyl group... 

The y-amino-p-hydroxy acid derived oxazolidinones 55 are prepared from the corresponding N-unprotected y-amino-p-hydroxy ester derivatives by reaction with phosgene,1119,391 carbonyl diimidazole,[41] or benzyl chloroformate.[86] Alternatively, cyclization is obtained from the N-carbamate protected derivatives, i.e. from the TV-isopropenyloxycarbonyl derivatives under heating,[381 or from the TV-Boc or N-Z derivatives under basic conditions. [68 81 87] By analogy, the p,y-diamino acid analogue is converted into the imidazolidinone 57 by treatment of the unprotected compound with phosgene.[83 88]... 

The elimination of water from (3-hydroxy-a-amino acid derivatives 28 is a particularly valuable method for the synthesis of DHAs 29, when the corresponding hydroxy compounds are readily accessible, such as, those of Ser, Thr and Ser( 3-Ph). 93 Some of the reagents recommended for the elimination of water are disuccinimidyl carbonate, 9495 l,l -carbonyl-diimidazole, 96 or a base and acetic anhydride. 97 Reaction of l,l -carbonyldiimidazole with arylidene Ser esters gives the corresponding DHA derivatives. 98 In the, presence of tri-ethylamine with terminally protected Ser and Thr residues in an inert solvent this reagent affords the AAla and AzAbu acid derivatives in good yields 96 (Scheme 10). This is perhaps one of the simplest and cleanest ways to prepare AAla and AAbu derivatives. 

The electrophilic one-carbon species can be an aldehyde, ketone, carboxylic acid, phosgene, thiophosgene, carbonyl diimidazole (CDI), etc., and the reaction essentially involves condensation with a 1,5-dinucleophile. The 1,5-dinucleophile invariably contains at least one heteroatom at a terminus, and more often than not two, so that the cyclization always involves the formation of at least one bond between carbon and a heteroatom. 

Amines can be linked to polymeric alcohols as carbamates. Carbamate attachment of amines can be achieved by reaction of isocyanates with alcohol linkers, or by treatment of alcohol linkers with phosgene [339,427,428] or a synthetic equivalent thereof, followed by exposure to the amine (Figure 3.26). The reagents most commonly used for the activation of alcohol linkers are 4-nitrophenyl chloroformate [69,429-436] and carbonyl diimidazole [427,437-440], The preparation of support-bound carbamates is discussed in Section 14.6. 

Alcohols and phenols can be attached to support-bound alcohol linkers as carbonates [467,665,666], although few examples of this have been reported. For the preparation of carbonates, the support-bound alcohol needs to be converted into a reactive carbonic acid derivative by reaction with phosgene or a synthetic equivalent thereof, e.g. disuccinimidyl carbonate [665], carbonyl diimidazole [157], or 4-nitrophenyl chloro-formate [467] (see Section 14.7). The best results are usually obtained with support-bound chloroformates. The resulting intermediate is then treated with an alcohol and a base (DIPEA, DMAP, or DBU), which furnishes the unsymmetrical carbonate. Carbonates are generally more resistant towards nucleophilic cleavage than esters, but are less stable than carbamates. Aryl carbonates are easily cleaved by nucleophiles and are therefore of limited utility as linkers for phenols. 

As alternatives to 4-nitrophenyl chloroformate, carbonyl diimidazole [100-102] or di-A-succinimidyl carbonate [103,104] can be used to convert polymeric alcohols into alkoxycarbonylating reagents suitable for the preparation of support-bound carbamates. Polystyrene-bound alkoxycarbonyl imidazole is less reactive than the corresponding 4-nitrophenyl carbonate, and sometimes requires heating to undergo reaction with amines. Additional activation of these imidazolides can be achieved by N-methylation (Entry 9, Table 14.7). 

Support-bound 1,2-diamines can be readily converted into imidazolidinones by treatment with carbonyl diimidazole [128,129]. The required diamines have been prepared on cross-linked polystyrene by reduction of peptides bound to MBHA resin with borane. Similarly, bicyclic imidazolines have been prepared from triamines and thiocarbonyl diimidazole (Entry 10, Table 14.3). Dehydration of polystyrene-bound monoacyl ethylene-1,2-diamines yields 4,5-dihydroimidazoles (cyclic amidines, Entry 5, Table 13.18). Several groups have reported the synthesis of 2-aminoimidazol-4-ones from resin-bound amino acid derivatives (e.g., Entry 6, Table 15.11). Most of these compounds are, however, unstable, and slowly decompose if dissolved in DMSO (Jesper Lau, private communication). 

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