N-Carbonyldiimidazole

CDI-activated hydroxyls also may undergo a side reaction to form active carbonates. This occurs when an imidazolyl carbamate reacts with another hydroxyl group before the second hydroxyl has had a chance to get activated with CDI. Particularly with adjacent hydroxyls on the same molecule, this can be a problem if a defined reactive species is desired. Any carbonates formed, however, are still reactive toward amines to create carbamate linkages. 

Formation of the activated species, whether with a carboxylate or a hydroxyl, must take place in nonaqueous environments due to the rapid breakdown of CDI by hydrolysis. Even in solvents containing small amounts of water, CDI quickly hydrolyzes to CO2 and imidazole. It is best to use solvents with less than 0.1 percent water to prevent extensive CDI breakdown. 

Aqueous reaction conditions that result in the best conjugation yields using CDI usually reflect the relative pK of the nucleophilic amine being coupled. Proteins are best coupled to CDI-activated supports or molecules in an environment at least one pH unit above their pi values. Frequently the greatest coupling yields occur in alkaline 

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First, the acid anhydride is produced by the reaction of the free acid with DCC. NucleophiUc attack by 4-pyrroUdinonepyridine on the anhydride results in the corresponding, highly reactive acylpyridinium carboxylate this leads to the formation of cellulose ester, plus a carboxylate anion. The latter imdergoes a DCC-mediated condensation with a fresh molecule of acid to produce another molecule of anhydride. N,N-carbonyldiimidazole (CDl) may substitute DCC for acid activation, the intermediate being N-acyhmidazol,... 

Enzymes modified with N -carbonyldiimidazole (CDI) include horseradish peroxidase 761 /1-lactamase after nitration and reduction,[771 lysozyme, and urease.[781 Ref. [77] describes how the tyrosine side chain of a protein was nitrated, reduced with dithionite to an amino group, and then treated with CDI or A/-(2,2,2-trifluoro-ethoxycarbonyl)imidazole to give the benzoxazolinonyl alanine moiety ... 

Aldoximes are readily dehydrated with N, N -carbonyldiimidazole (CDI). An intermediate azolide is formed in the process under elimination of one mole of imidazole, which fragments into a nitrile through elimination of CO2 and a second mole of imid-azole.[1],[2]... 

In related work, complexes 32 and 33 have been synthesized (41). The precursor complex in each preparation is the rhenaacetylacetonimine complex 25, where R = CH2CH2OH. This complex is formed by direct Schiff-base condensation with 2-aminoethanol. Complex 32 is formed when this precursor compound is treated with MeP(0)F2, and complex 33 is formed similarly by treatment with N,N -carbonyldiimidazole. The... 

Figure 25.8 N,N -carbonyldiimidazole (CDI) may be used to activate the terminal hydroxyl of mPEG to an imidazole carbamate. Reaction of this intermediate with an amine-containing compound results in the formation of a stable carbamate linkage.

Cyclic ureas, —NHC(0)NH—, have been similarly produced using carbonyl chloride, N,N -carbonyldiimidazole, carbon monoxide, thiocarbonyl chloride or carbon disulfide... 

EtjN,663 and N,N -carbonyldiimidazole (100).664 In the latter case easily alcoholyzed im-idazolides (101) are intermediates. BF3 promotes the esterification by converting the acid to RCO+ BF3OH, so the reaction proceeds by an AacI type of mechanism. The use of BF etherate is simple and gives high yields.665 Carboxylic esters can also be prepared by treating carboxylic acids with /-butyl ethers and acid catalysts.666... 

Alkytidene cyclopropanesThese compounds (3) can be prepared by reaction of aldehydes and ketones with 1-methylseleno-l-lithiocyclopropane (1) to give /)-hydroxycyclopropyl selenides (2). Elimination of CHjSeOH is then effected with N.N -carbonyldiimidazole or PI, for substrates derived from ketones. 

Potassium cyanate, carbonic and chlorocarbonic esters, phosgene, or urea are used as cyclizing agents in the synthesis of perimidine-2-one 430 (X = X = NR, Y = O) and its derivatives from 1,8-naphthylene-diamines. Naphtho[substituted amino group in position 2 (X = Y = NH or Y = NR) are obtained on interaction of 1,8-naphthylenediamines with bromocyanogen, cyanoamide, 5-methylisothiourea, arylisothiocyanates, or dimethyltri-chloromethylamine. 

Methyl esters may be prepared by reaction of the aromatic carboxylic acid with diazomethane (cf. Section 4.2.25, p. 433) or, more conveniently, by reaction with a boron trifluoride-methanol reagent. The latter procedure is illustrated by the preparation of methyl m-chlorobenzoate and dimethyl terephthalate (Expt 6.164). t-Butyl esters may be prepared by conversion of the acid into an N-acylimidazole by reaction with N,N -carbonyldiimidazole, followed by reaction with t-butyl alcohol in the presence of DBU62 (Expt 6.165). 

N,N -Carbonyldiimidazole (1.65 g, 10 mmol) was added to a solution of o-chlorobenzoic acid (1.57g, lOmmol) in dimethylformamide (10ml) held under nitrogen, and the mixture was stirred for 1 hour at 40 °C. t-Butyl alcohol (1.48 g, 20mmol) and DBU (l,8-diazabicyclo[5.4.0]undec-7-ene, 1.52 g, 10 mmol) were added and the mixture stood for 24 hours at 40 °C. Ether (100 ml) was then added, and the solution was washed with 10 per cent hydrochloric acid (20 ml), water (20 ml), aqueous potassium hydrogen carbonate (20 ml) and dried over anhydrous sodium sulphate. The solvent... 

This salt is prepared by treatment of N,N -carbonyldiimidazole with methanesul-fonic acid (2 equiv.). 

Ethyl 9-(N-ethy l-N-phenylcarbamoylthio)-4-oxo-4 -pyrido[ 1,2-a]py-rimidine-3-carboxylate 517 was obtained when 9-mercaptopyridopyrim-idine-3-carboxylate 513 (R1 = COOEt, R2 = H) was first reacted with N.N -carbonyldiimidazole in dichloromethane for 1 hour, and then the reaction mixture was treated with N-ethylaniline for another 16 hours (87EUP218423). 

CAN Ceric ammonium nitrate CDI N,N -Carbonyldiimidazole DCC N,N -Dicyclohexylcarbodiimide DIC N,N -Diisopropylcarbodiimide DMAP 4-(Dimethylamino)pyridine DMF N,N-Dimethylformamide DMSO Dimethyl sulfoxide... 

N,N -carbonyldiimidazole (CDI) 29 is used to protect the 3- and 4-OH group of the galactal 6 as a cyclic carbonate.6 The first report of a cyclic carbonate was in 1883 by Nemirowsky He treated ethylene glycol with phosgene (30). Phosgene is known as a highly toxic... 

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