1.1- carbonyldiimidazole

Another compound 9 with three heterocyclic rings linearly fused (5 5 5) with two heteroatoms has been prepared from 1,1 -carbonyl diindole 297 <2001T5199>. Palladium-mediated coupling of the 2- and 2 -positions of 297 afforded the 1,1 -carbonyl-2,2 -biindolyl 9. 1,1 -Carbonyl diindole 297 was in turn obtained in 41% yield from 1,1 -carbonyldiimidazole 296 by reaction with indole in DMSO at 125 °C. The palladium-catalyzed coupling step afforded the desired product 9 in low yield and required a stoichiometric amount of palladium acetate. Therefore, it was felt prohibitively expensive. Addition of various co-oxidants (Ac20, Mn02, and Cu(OAc)2, etc) to make the reaction catalytic in palladium did not result in any improvement of the yield of 18 (Scheme 53). 

By working quickly, the imidazolium chloride may be removed by suction filtration through a Buchner funnel. However, the precipitate should not be freed of solvent completely because imidazolium chloride is extremely hygroscopic. If the moist precipitate is washed with 50-100 ml. of anhydrous tetrahydrofuran, the yield of 1,1 -carbonyldiimidazole may be slightly increased however, there is some danger of the introduction of too much moisture into the reaction solution. 

In order to obtain a purer product the crude material may be recrystallized from hot anhydrous tetrahydrofuran with careful exclusion of moisture. After this operation the yield is reduced to 65-75% the m.p. is then between 114° and 118° e.g., recrystallization of 24.8 g. (91%) of 1,1 -carbonyldiimidazole from 60 ml. of anhydrous tetrahydrofuran yielded 19.9 g. (73%) m.p. 116-118°. 

Carbonyldiimidazole has been used for the preparation of such compounds as esters, anhydrides, amides, peptides, ketones, ethers, and isocyanates.2 The present procedure provides a convenient method for its preparation in good yield. 

Wang resin was purchased from Advanced ChemTech (1% DVB, 0.70mmol/g substitution, 100-200 mash, Cat. SA5009). Anhydrous tetrahydrofuran (THF), A/A-dimcthyl-formamide (DMF), methanol, dichloromethane, pyridine, 1,1 -carbonyldiimidazole (CDI), piperazine, homopiperazine, trans-1,4-diaminocyclohexane, 4-(dimethylamino)pyridine (DMAP), succinic anhydride, diglycolic anhydride, 3-methyl-glutaric anhydride, 2-aminophenol, 2-amino-p-cresol, 2-amino-4-tert-butyl phenol, /V-methylmorpholine (NMM), triphenylphosphine, diethyl azodicarboxylate (DEAD), and trifluoroacetic acid (TFA) were purchased from Aldrich Chemical Company, Inc. and used without further purification. PyBOP was purchased from Novabiochem. 

Amino-l-carboxamides 288 (cis, n = 1, 2 tram, = 2 R = Ph, substituted aryl) were cyclized to dihydrouracils 289 with 1,1 -carbonyldiimidazole (CDI) with the retention of configuration (90T1943). The diexo-fused 290 was prepared by the same method (87T1921). 

Scheme 8 Synthesis of a Protected Depsipeptide through the Ester Bond Condensation of Peptides by the 1,1 -Carbonyldiimidazole Method 871...

Methyl acetoacetate, 60 p-(Tolylsulfinyl)methyllithium, 115 Intramolecular acylation 1,1 -Carbonyldiimidazole, 66 of organometallic reagents to form carbonyl compounds... 

Miscellaneous reactions Allyl chloroformate, 9 1,1 -Carbonyldiimidazole, 66 Di-r-butyl dicarbonate, 94 Di- n-carbonylhexacarbonyldicobalt, 99 Palladium(II) acetate-Triphenylphos-phine, 233... 

Y/ .v-(3-Lactains have also been obtained by the Staudinger reaction carried out between divinylimine and /V-acylimidazoles possessing an electron-withdrawing group (EWG) in a position [111]. This latter were prepared by treatment of a-EWG substituted carboxylic acids with 1,1-carbonyldiimidazole. 

A solution of 2-(2-amino-5-chlorophenyl)-4-cyclopropyl-l,l,l-trifluoro-3-butyn-2-ol (15.00 g, 0.0518 mol) and 41.98 g (0.259 mol) of 1,1 -carbonyldiimidazole in 250 mL of dry THF was stirred under argon at 55°C for 24 hours. The solvent was removed on a rotary evaporator and the residue was partitioned between 500 mL of ethyl acetate and 400 mL of water. The layers were separated and the aqueous phase was extracted once more with ethyl acetate. The combined ethyl acetate extracts were washed with 2 times 200 mL of 2% aqueous HCI, saturated aqueous NaHC03, and brine. Drying over MgS04, filtration, and removal of the solvent in vacuo provided 16.42 g of the title compound as a solid. Recrystallization from ethyl acetate/hexane afforded 12.97 g of analytically pure ()-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-l,4-dihydro-2H-3,l-benzoxazin-2-one as a white crystals. Melting point 178°-180°C. 

Dehydrative cyclization of A-(4-methoxyphcnyl) protected 7-aminoalcohols 157 by the Staab reagent (1,1 -carbonyldiimidazole, CDI) led to the formation of iV-(4-methoxyphenyl)azetidines 158 (Equation 37) <2004SL2751>. The reactions were carried out in a Kugelrohr apparatus. The imidazole formed in the reaction was separated by filtration through silica gel. 

Preparation of the tripeptide component is outlined in Scheme 2. The glycine benzyl ester was coupled to commercially available f-Boc-glycine using 1,1-carbonyldiimidazole as coupling agent. Removal of the carbamate on the N-terminus (TFA) furnished 4 in 90% yield (two steps). Compound 4 was coupled... 

Fig. 6 Immobilized functional nucleic acids, a Example fabrication of an aptamer biosen- sor surface (i) Attachment of (glycidoxypropyl)trimethoxy silane (GOPS) to glass surface at low pH results in the formation and subsequent cleavage of an epoxide, (ii) The resultant diol is activated with 1,1-carbonyldiimidazole (CDI) to form a carbonylimidazole.

A reactor was charged with the Step 1 product (20 g), THF (445 g), and 1,1 -carbonyldiimidazole (7.50 g) and then stirred for 1 hour at ambient temperature. The mixture was treated with the dropwise addition of l-(l-naphthyl)ethylamine (7.9 g) dissolved in THF (67 g) over 20 minutes and then stirred for 48 hours at ambient temperature. The mixture was concentrated to one-third its volume and precipitated in 200 ml water. The residue was extracted five times with 200 ml of water, ground in a blender and dried, and the product isolated was in 84% yield. 

Paul R, Anderson GW. N,N -carbonyldiimidazole, a new peptide forming reagent. J. Am. Chem. Soc. 1960 82 4596-4600. Bethell GS, Ayers JS, Hancock WS, Hearn MTW. Novel method of activation of cross-linked agaroses with 1,1 -carbonyldiimidazole which gives a matrix for affinity chromatography devoid of additional charged groups. J. Biol. Chem. 1979 254 2572-2574. 

Hearn MTW, Bethell GS, Ayers JS, Hancock WS. Application of 1,1 -carbonyldiimidazole-activated agarose for the purification of proteins. 2. Use of an activated matrix devoid of additional charged groups for the purification of thyroid proteins. J. Chromatog. 1979 185 463-470. 

A solution of p-toluic acid (6.8g, 50mmol) in THF (80ml) and 1,1 -carbonyldiimidazole (7.2g, SOmmol) in THF (80ml) is allowed to stand... 

Among the most useful of these azolides is 1,1 -carbonyldiimidazole (253). This compound is extremely reactive towards nucleophilic reagents because the carbonyl group is subject to electron withdrawal from both sides. Also, although it is very rapidly hydrolyzed by water at room temperature with vigorous carbon dioxide evolution, the compound is crystalline, and much more easily handled than phosgene which has similar reactivity. In the formation of 1-acylimidazoIes compound (253) reacts in equimolar proportions with a carboxylic acid in an inert solvent to give practically quantitative yields. This reaction comprises a two-step mechanism (Scheme 145) in which the carboxylic acid reacts initially... 

Compared with 1,1 -carbonyldiimidazole, COMODD is a crystalline, stable and non-hvgroscopic compound. MODD released after use of COMODD as coupling reagent is water soluble and therefore can be easily recycled. Moreover, in contrast to imidazole, MODD is acidic (pKa measured at 20°C 3.6). This characteristic can be very useful in the case of substrates sensitive to basic conditions. 

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