Dicyclohexyl carbodiimide reaction

Mechanism of amide formation by reaction of a carboxylic acid and an amine with dicyclohexyl-carbodiimide (DCC). 

Poly (ethylene oxide) macromonomers72 761 are made in a similar way, as the alkoxide end group is reactive enough towards benzylic halides. With methacryloyl chloride, side reactions are involved. It is better to first protonate the PEO, and then to have it react with methacryloyl chloride in the presence of some triethyl amine. One can also react co-hydroxy polyethylene oxide) with methacryloyl imidazole, or with methacrylic acid in the presence of dicyclohexyl carbodiimide (DCCf)77). 

The reaction between acyl halides and diazomethane is of wide scope and is the best way to prepare diazo ketones. Diazomethane must be present in excess or the HX produced will react with the diazo ketone (10-74). This reaction is the first step of the Amdt-Eistert synthesis (18-8). Diazo ketones can also be prepared directly from a carboxylic acid and diazomethane or diazoethane in the presence of dicyclohexyl-carbodiimide. ... 

In 1974 the first example of asymmetric induction in an intramolecular Pummerer reaction was observed and reported. Stridsberg and AUenmark (300) treated optically pure o-benzylsulfinylbenzoic acid 271 with acetic anhydride in the presence of dicyclohexyl-carbodiimide (DCC) and found that the Pummerer reaction product, 3,l-benzoxathian-4-one 272, was optically active. The sign and optical rotation values ([alp varied from +42° to -11°) of 272... 

A reactor charged with 4-ethynylbenzoic acid (2.01 mmol) dissolved in dimethylacetamide was treated with 1-hydroxybenzotriazole (2.01 mmol) and /V.V -dicyclohexyl-carbodiimide (2.07 mmol) and stirred for 2 hours at ambient temperature. The mixture was then treated with (S)-(+)-decylalaninate (2.13 mmol) and stirred at ambient temperature for 3 hours and then at 120°C for a further 3 hours. The reaction was filtered, concentrated, and the residue purified by a silica gel chromatography using chloroform and ethyl acetate. After recrystallization from hexane 0.33 g of product was isolated as a crystalline solid. 

However, the reaction of the binuclear rj2-thioaldehyde titanocene complexes 112 (see Scheme 26) with valeronitrile, benzonitrile, and methyl thiocyanate proceeded in a similar fashion (Scheme 39).69 Related metalla-cyclic compounds were also obtained from the reactions of 112 with benzo-phenone (Scheme 39), various imines, phenyl isothiocyanate, or dicyclohexyl carbodiimide via insertion of the C = 0 and C = N bond, respectively, into the Ti-C bond.69,70... 

Equimolar quantities of benzhydrol and the phosphorane (3a) were also reacted in dimethyl sulphoxide solution. Apart from bis(benzhydryl) ether (18%) and catechol monobenzhydryl ether (39%), a small amount of benzophenone (17%) was obtained. It was shown that, in the absence of phosphorane, benzhydrol is not oxidised to benzophenone by dimethyl sulphoxide. Reaction similar to that outlined in Scheme 1 is a likely possibility. Again, the alcohol is activated by reaction with the phosphorane toward nucleophilic attack, in this case by dimethyl sulphoxide. Significantly, oxidation of alcohols by dimethyl sulphoxide is usually carried out using the Pfitzner-Moffatt reagent (dicyclohexyl carbodiimide and anhydrous phosphoric acid in dimethyl sulphoxide) (13) whereas the reaction using the phosphorane (3a) is carried out under neutral conditions. Unfortunately, however, attempts to improve the yield of benzophenone have hitherto failed. 

The above obtained [(4S)-4-Methyl-5-oxo-2-(tribromomethyl)-l,3-dioxolan-4-yl]acetic acid (102.5 mg 0.250 mmol) and 2-mercaptopyridine- N-oxide (34.4 mg 0.280 mmol) were suspended in CBrCI3 (1.5ml). The reaction mixture was heated to reflux and a solution of dicyclohexyl carbodiimide (DCC) (103 mg 0.500 mmol) in CBrCI3 (1.0 ml) was added slowly over the course of 30 min. The reaction mixture was stirred for an additional hour. The product was purified by silica gel chromatography (CH2CI2/hexanes (1 2)) and was obtained as white needles from the same solvents. Yield 72 mg (65%) mp 110-113°C. 

As the last example of an SN reaction at the carboxyl carbon of a carbonic acid derivative, consider the synthesis of dicyclohexylurea in Figure 6.30. In this synthesis two equivalents of cyclohexylamine replace the two methoxy groups of dimethyl carbonate. Dicyclohexylurea can be converted into the carbodhmide dicyclohexyl-carbodiimide (DCC) by treatment with tosyl chloride and triethylamine. Thereby, the urea is effectively dehydrated. The mechanism of this reaction is identical to the mechanism that is presented in Figure 7.5 for the similar preparation of a different carbodiimide. 

Esterification with alcohols in the presence of pyridine was used by Felder et al. [36]. Water produced in the reaction mixture is bound by the addition of N,N -dicyclohexyl-carbodiimide (Scheme 4.8). The acid (ca. 10 mequiv.) is dissolved in 25 ml of alcohol and 4 ml of pyridine and an excess of dicyclohexylcarbodiimide (12 mequiv.) are added (even more if the sample is not dry). The amount of pyridine can also be larger and it then acts as a solvent, e.g., if the alcohol used is solid (menthol). The mixture is then stirred at room temperature only with some higher alcohols or acids must the mixture be heated at 40—80°C for 30—120 min. If a precipitate of N,N -dicyclohexylurea is produced in the reaction, it is allowed to sediment and, after adding an internal standard,... 

Although there are many methods available, there are two main routes for the synthesis of nucleoside monophosphates. These involve either the reaction of the nucleoside with 2-cyanoethylphosphate in the presence of a condensing agent such as dicyclohexyl carbodiimide (DCC)2,3 or phosphorylation of the nucleoside... 

Heating of the cycloadduct derived from 4-nitrophenyl isothiocyanate and dicyclohexyl-carbodiimide causes cycloreversion to give the starting materials In the reaction of phenylcarbonyl isothiocyanate and substituted phenylcarbonyl isothiocyanates, respectively, with carbodiimides, [2-1-4] cycloadducts 221 are usually obtained, but the [2 + 2] cycloadduct 220 is also formed when the reaction of DCC with phenylth-iocarbonyl isothiocyanate is stopped at shorter reaction times. ... 

The 5-nitro substituted dipeptide analogue was formed by selective reduction (BH,) of methyl 3-amidocarbonyll-5-nitrobenzoate, followed by deesterification (LiOH in THF) and reaction sequentially with Fmoc-Asp-(tBu)-OH and H-Gly-Asp(tBu -Gly-OH (dicyclohexyl carbodiimide (DCC), N-hydroxysuccinimide) to yield Fmoc-Asp(tBu)-5N023 amb-Gly-Asp (tBu)-GlyOH. CycUzation with 4-dimethylaminopyridine (DMAP) and 2-lH-benzotriazole-1-yl-l, 1,3,3,-tetramethyluronium tetrafluoroborate (TBTU) was achieved in 70% yield, followed by reduction (Hj, Pd/C) to give the amino-substituted peptide loop 2. (p. 2681)... 

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