N -Carbonyl Diimidazole

Most of the reactions and properties of 1-substituted imidazoles have been discussed earlier in this review. Apart from the utilization of the readily removable benzyl substituent in synthetic procedures leading to 2-substituted imidazoles, perhaps the mostexciting advances have stemmed from the reactions of the 1 -acylimidazoles (imidazolides) which are extremely reactive in such nucleophilic reactions as hydrolysis and alcoholysis.12 The use of such compounds as N,N -carbonyl-diimidazole in peptide synthesis is now commonplace. The silicon-nitrogen bond in N-trimethylsilylimidazoles is also extremely reactive, so reactive that it is attacked by a-halogenocarboxylic esters.361... 

Carbonylation of organoboranes Carbon monoxide. N,N -Carbonyl-diimidazole. 2,3-Dimethyl-2-butylborane. Hydrogen fluoride—Antimony pentafluoride. Lithium trimethoxyaluminum hydride. Palladium (II) chloride. 

Hierzu setzt man aquimolare Mengen Carbonsaure, Alkohol und N,N -Carbonyl-diimidazol in einem indif-ferenten Losungsmittel (wie z.B. THF, Benzol, Chloroform Oder Dimethylformamid) um95. 

Benzoesaure-phenylester95 Zu 2,44 g (20 mmol) Benzoesaure in 30 ml trockenem THF werden bei 20° 3,24 g (20 mmol) N,N -Carbonyl-diimidazol gegeben. Nach beendeter Kohlendioxid-Entwicklung werden 1,84 g (20 mmol) Phenol zugegeben und 1 Stde. unter RuckfluB erwarmt. Nach Abziehen des THF wird der Riickstand mit Wasser gewaschen und getrocknet Ausbeute 3,37 g (85%) Schmp. 70°. 

The commercially available and easily handled crystalline solid W,N -carbonyl-diimidazole (CDI) is utilized as a starting reagent for the general synthesis of unsymmetrical tetrasubstituted ureas. The intermediate carbamoyl imidazole 1017 is first obtained by reaction of CDI with a secondary amine. Compound 1017 is then converted into the more reactive and resonance-stabilized imidazolinium salt 1018 by N-alkylation of the imidazole moiety. Addition of a different secondary amine to 1018 furnishes N,N,N, N -unsymmetrical tetrasubstituted ureas 1019 in high yield (72-99%). 

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]... 

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). 

To a solution of 3.4 kg N-phthalimidoacetic acid in 20 L of methylene chloride was added a solution of 2.8 kg of 1,1-carbonyl diimidazol in 20 L of methylene chloride. The mixture was refluxed for 1 hour. After cooling to the obtained solution was added a solution of 4.3 kg of 2-amino-3-benzoyl-4,5-tetramethylene thiophene in 30 L of methylene chloride and the reaction mixture was refluxed for 16 hours. After cooling the mixture was washed with 30 L of water, dried with sodium sulfate and filtered. After removing the solvent was obtained the 2-(N-phthalimidoacetylamino)-3-benzoyl-4,5-tetramethylene thiophene, yield 70%, melting point 230°C. 

Dimethyl-4-oxo-l,4-dihydro-l,7-naphthyridine-3-carboxylic acid with l-(4-ami-nobutyl)-4-diphenylmethylpiperazine gave A-[4-(4-diphenylmethylpiperazin-1 -yl)butyl -6,8-dimethyl-l, 7-naphthyridin-4(l//)-one (7) (substrate, N, iV-carbonyl-diimidazole, Me2NCHO, 60°C, 5 h then substrate in, 60°C, 1 h 50%).1204... 

Ozonolysis of the alkene frees the carboxylic acid, which reacts with carbonyl diimidazole (GDI) n a nucleophilic substitution at the carbonyl group. The relatively stable imidazole anion is the ea ing group. The anion of nitromethane displaces the second imidazole anion and completes the uence. 

The synthesis of alkylidene cyclobutanes from l-(l-seleno) cyclobutyl carbinols is much easier than the one reported for analogous compounds with a cyclopropyl group and readily occurs on their reaction with a large variety of reagents 7 9 n,)2) especially PI3 at 20 °C or carbonyl diimidazole at 110 °C (Scheme 50 k) Alkylidene cyclobutanes have also been prepared on reaction of l-(l-hydroxy)-l-(l -selenoalkyl)cyclobutanes... 

This amino acid which is synthesized by muscle and excreted into urine without recycling has been methylated with [Djj-methyl iodide exclusively at N site and applied as tracer in vivo and as an isotopic dilution standard in vitro, by protecting the N and N positions in a cyclic urea derivative 34. The latter was obtained by treating the (5)-histidine methyl ester 35 with carbonyl diimidazole and hydrolysing the product 36 in boiling dilute hydrochloric acid to give isomerically and isotopically pure title compound 37 retaining at least 95% of its optical rotation (equation 5). 37 has been applied in clinical research. 

Deduce structures for the pyrones formed by the following sequences (i) PhCOCH3 with PhC C02Et in the presence of NaOEt (ii) butanoic acid heated with PPA at 200 °C (iii) n-BuC0CH2C02H with carbonyl diimidazole (iv) PhCOCH2COCH3 with excess NaH then methyl 4-chlorobenzoate (v) CH3COCH=CHOMe with KOt-Bu and PhCOCl. 

Hydroxyamino)benzodiazepine (90) is acylated on oxygen upon reaction with acid chlorides (acetyl or benzoyl chloride) or isocyanates (methyl isocyanate) in the cold. On heating with acetic anhydride at 100°C, there is an oxido-reductive rearrangement to give the 3-acetoxy-2-methylamino derivative (91) (Scheme 14). This is considered to proceed by isomerization of the nitronium ion formed by cleavage of the N—O bond to the 3-carbonium ion which is trapped by the nucleophile (acetate) <80AP(313)926>. A similar mechanism is used to explain the formation of the 3-(l-imidazolyl) derivative (92) on reaction of (90) with carbonyl diimidazole. 

N, iV -Carbonyl Diimidazole Cerium(lV) Ammonium Nitrate OT-Chloroper benzoic Acid A-Chlorosuccinimide Chlorotrimethylsilane Chlorotris(triphenylphosphine)-rhodium(l)... 

Mediators covalently bound to or complexed with conducting and other polymers have been termed wires. Wired enzyme glucose electrodes were produced by the electropolymerization of (ferrocenyl)amidopropyl pyrrole (FAPP Fig. 6, structure 1) in the pre.sence of glucose oxidase [95], FAPP was synthesized by using l,r-carbonyl diimidazole to link ferrocenecarboxylic acid to A -(3-aminopropyl) pyrrole. The electropolymerization of Os(2,2 -bipyridine)2(3-pyrrol-l-ylmethylpyridine)Cr (Fig. 6, structure 2), N-methylpyrrole, and pyrrole-modified... 

N-Substituted caprolactams were imexpectedly formed by the reaction of an alcohol or carboxylic acid with carbonyl diimidazole and 1.8-diazabicy-cloundecane (DBU). In these reaaions, DBU acts as a nucleophile on an N-acylimidazole intermediate to produce the acylated DBU intermediate 2 which undergoes hydrolytic ring opening to give excellent yields of the N-substituted caprolactam derivatives 3 (13TL5181). 

The acyl carbon of readily available amino acids such as alanine can be converted to a ketone moiety by activation of the acid with carbonyl diimidazole (CDI) and then condensation with an enolate, such as the magnesium enolate of malonic acid, mono ethyl ester. In this particular example, N-Boc alanine was converted to 1.206 using this method O Catalytic hydrogenation of the ketone moiety gave the alcohol group in 1.207, and conversion to the chloride and base induced dehydrohalogen-ation gave ethyl 4-(N-Boc amino)pent-2-enoate (7.205). 

The acid moiety of an amino acid can be activated for acyl substitution rather than converted to an aldehyde for acyl addition. Boc-alanine was converted to an acyl imidazole by reaction with carbonyl diimidazole (CDI see chapter two, section 2.4), and then condensed with the magnesium enolate of the mono ethyl ester of malonic acid to give keto-ester 5.9. Subsequent catalytic hydrogenation of the ketone moiety gave ethyl 3-hydroxy-5-(N-Boc amino)penlanoate, 5.10 Once the o... 

Finally, Liu and coworkers have employed the deearho>ylative allylation approach to the one-pot synthesis of allylic N-g yeosyl imidazole analogues, e.g. 32, by reaction of 3-OH glycals, Le. 29, with carbonyl diimidazole derivatives, (30) in the presence of Pd(PPhs)4, which takes plaee via in situ formed intermediate allylic carbamates, i.e. 31 (Scheme 12)/ ... 

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