Di-2-pyridyl carbonate

A. K. Ghosh, T. T. Duong, and S. P. McKee, Di(2-pyridyl) carbonate promoted alkoxycar-bonylation of amines A convenient synthesis of functionalized carbamates. Tetrahedron Lett. 32 4251 (1991). 

Polymer-bound reagents have also been used. The synthetically important Weinreb amides [RCON(Me)OMe, see 16-82] can be prepared from the carboxylic acid and MeO(Me)NH HCl in the presence of tributylphosphine and 2-pyridine-A -oxide disulfide. Di(2-pyridyl)carbonate has been used in a related reaction that generates amides directly. The reaction of a carboxylic acid and imidazole under microwave irradiation gives the amide. Microwave irradiation of a secondary amine, formic acid, 2-chloro-4,6-dimethoxy[l,3,5]tria-zine, and a catalytic amount of DMAP (4-dimethylaminopyridine) leads to the formamide. ° Ammonium bicarbonate and formamide converts acids to amides with microwave irradiation. Lactams are readily produced from y- or 8-amino acids, for example. 

DCC-DMAP has been used in the synthesis of depsipeptides. Macrocyclic lactones have been prepared by cyclization of hydroxy carboxylic acids with DCC-DMAP. The presence of salts of DMAP, such as its trifluoroacetate, is beneficial in such cyclizations, as shown for the synthesis of a (9. -dihydroerythronolide. Other macrolactonizations have been achieved using 2,4,6-Trichlorobenzoyl Chloride and DMAP in Triethylamine at rt or Di-2-pyridyl Carbonate (6 equiv) with 2 equiv of DMAP at 73 °C. ... 

Pyridone and phosgene in tetrahydrofuran give di-(2-pyridyl) carbonate (XII-(H)4). Ethyl pyrocarbonate and pyridinols in aqueous ethanol give the corresponding pyridyl ethyl carbonates. ... 

S,S-Dimethyldithio Diphenyl carbonate (DPhC) Di-2-pyridyl carbonate (DPC) 1,1-Carbonyldiimidazole (CDI)... 

The reaction of di(2-pyridyl) carbonate (DPC) 725 with a variety of alcohols, including hindered secondary, tertiary, and protected glycols, afforded the corresponding mixed carbonates, which were efficiently transformed into various carbamates in high yield under mild conditions. DPC is quite stable and can be stored at room temperature for several months without any noticeable decomposition. This method has allowed the preparation of a variety of functionalized carbamates (Table 4.24), overcoming many of the limitations associated with the alkoxycar-bonylation methodologies [505]. 

A versatile reagent for a convenient synthesis of various functionalized carbamates (see Section 4.3.2), ureas, interchanged carbonates, and active esters for activation in forming peptide bonds, as well as for the direct esterification of carboxylic acids [635-637] (see also Section 4.3.3.7), is di-2-pyridyl carbonate, DPC, 725. It is prepared from commercially available 2-hydroxypyridine and phosgene in 90% yield [638]. 

Typical procedure. Di-2-pyridyl carbonate, DPC, 725 [638] A solution of phosgene (for a safe source, see Chapter 7) (2.5 m in toluene, 2 mL, 5.0 mmol) was diluted with dichloromethane (8 mL) and then a solution of 2-pyridinol 853 (950 mg, 10 mmol) and triethylamine (1.214 g, 10.2 mmol) in dichloromethane (20 mL) was added at 0 °C. The reaction mixture was stirred at 0 °C for 1 h, then washed with cold 5% NaHCOs solution (20 mL) and cold saturated brine (20 mL), dried over MgS04, and filtered. The filtrate was concentrated to dryness to give di-2-pyridyl carbonate, DPC, 725 (972 mg) in 90% yield. It was recrystallized from dichloro-methane/petroleum ether (811 mg, 75%) mp 84—86 °C. 

Typical procedure. Di-2-pyridyl carbonate hydrochloride, DPC-HCI, 877 [639] Avoid sunlight (2-hydroxypyridine is light-sensitive) and work in a well-ventilated fUmehood. In a 2-L three-necked flask equipped with a gas inlet tube, stirrer, and reflux condenser, 2-hydroxypyridine 724 (47.5 g, 500 mmol) was dissolved in absolute THF (750 mL) with stirring and mild warming. Phosgene (for a safe source, see Chapter 7) (12.4 g, 8.9 mL, 125 mmol) was passed into the solution, and then nitrogen was... 

The reagent 1292 can be conveniently prepared in 94% yield by the addition of N,0-dimethylhydroxylamine hydrochloride 1291 and triethylamine to a solution of di-2-pyridyl carbonate (DPC) in dichloromethane at 0 °C. It is easily separated by aqueous work-up (2-hydroxypyridine is very soluble in water) and purified by column chromatography on silica gel or kugelrohr vacuum distillation (bp 116-120 °C/0.20 mmHg). This phosgene equivalent shows no sign of decomposition when kept for two months in a refrigerator. 

Typical procedure. p-Methoxyvalerophenone 1294k [963] Preparation of N-Methoxy-N-methyI-2-pyridyI urethane 1292 To a solution of di-2-pyridyl carbonate (2.162 g, 10 mmol) in dichloromethane (30 mL), N,0-dimethylhydroxylamine hydrochloride 1289 (975.5 mg, 10 mmol) and triethylamine (1.42 mL, 10.2 mmol) were added at 0 °C. After stirring for 1 h at 0 °C, the reaction mixture was allowed to warm to room temperature over a period of 1 h. It was then poured into saturated aq. NaHCOj solution (60 mL) and the aqueous phase was extracted with dichloromethane (3 X 30 mL). The combined organic extracts were dried over MgS04, filtered, and concentrated to dryness in vacuo. The crude product was purified by... 

The preparation of mixed carbonates and their transformaticMi to fiinctionaUzed carbamates by use of di(2-pyridyl) carbonate has been reported. A caibdiydrate example is given in Scheme 12. ... 

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