Triphosgene reaction with, pyridine

Interestingly, the chloroformate (diphosgene) and the carbonate (triphosgene) react with pyridine to give the same product (see also Chapter 12). The material described as (py)j. jCOClj, prepared from the reaction of phosgene with pyridine in benzene solution, was noted to lose half a molar equivalent of pyridine upon standing over PjOj in vacuo [1809a]. 

Transesterification has been carried out with phase-transfer catalysts, without an added solvent. Nonionic superbases (see p. 365) of the type P(RNCH2CH2)3N catalyze the transesterification of carboxylic acid esters at 25°C. ° Silyl esters (R C02SiR3) have been converted to alkyl esters (R C02R) via reaction with alkyl halides and tetrabutylammonium fluoride. Thioesters are converted to phenolic esters by treatment with triphosgene-pyridine and then phenol. 

Carbamoyl chlorides. A direct preparation of carbamoyl chlorides from tertiary benzylamines (debenzylation) is by reaction with triphosgene. A-Methoxy-N-methyl-carbamoyl chloride, which is useful for coupling with various unsaturated organostannanes, is obtained from chloroformylation of the methoxylamine in the presence of pyridine. ... 

Microwave irradiation can be used to make oxazolo[4,5-fc]pyridines and allows reaction with amides in lieu of acids when urea or thiomea are used, 2-ones (2-thiones) are obtained carbon disulfide with potassium hydroxide also leads to 2-thiones. The use of triphosgene and 2,3-diamino-pyridines can be used to made the analogous imidazo[4,5-b]pyridin-2-ones. Reaction with cyanogen bromide gives... 

The amides 23, i.e., the products from the reaction of the anhydride (1) and the acetylenic amides 21 (see part 1), undergo cyclization to the derivatives of oxazoloquinazoline 275 (yields 31-50%) when treated with triphosgene in pyridine. The configuration of the initial amines 21 and amides 23 is retained [10],... 

N-(Phenoxycarbonyloxy)thiopyridone derivatives 99 are efficient iinimolecular photochemical sources for the clean generation of phenoxyl radicals. They are prepared by the reaction of lithium phenoxides with phosgene (from triphosgene and pyridine in a 1 3 molar ratio) [56]. 

Typical procedure. 3,3,3-Trinitropropyl carbamate 122 [65] To a stirred mixture of triphosgene (1.8 g, 6 mmol) and 3,3,3-trinitropropanol (3.1 g, 16 mmol) in di-chloromethane (10 mL) at 0 °C, a solution of pyridine (1.5 mL, 19 mmol) in dichloromethane (5 mL) was added dropwise. After 24 h at room temperature, the reaction mixture was cooled to —10 °C, whereupon concentrated ammonium hydroxide (30%, 2 mL, 32 mmol) was added dropwise with stirring. The precipitated solid was removed by filtration and the filtrate was extracted with water and dilute hydrochloric acid. The volatiles were removed to give 2.75 g of product, which was chromatographed on silica gel 40 (eluting first with dichloromethane and then with dichloromethane/acetone, 80 20) to yield 0.65 g of solid mp 82-84 °C. 

Reaction of triphosgene in the presence of pyridine with a variety of 1,2- and... 

Oxazoloquinazolines 1134 and oxazoles 1135 have been prepared from o-amino-N-(l,l-disubstituted-propynyl)benzamides 1133 with triphosgene by angular cydi-zation, promoted by either the initial exothermic reaction on the addition of triphosgene and/or by refluxing in pyridine [805]. 

Ceneral procedure. 2-Methylene-3,3-disubstituted-oxazolo[2,3-b]quin-5(3H)-ones 1134 [805] To a well-stirred and ice-cooled solution of an o-amino-N-(l,l-disubstituted-propynyl)benzamide 1133 (5 mmol) in pyridine (15 mL) was added triphosgene (5 mmol). The reaction mixture was allowed to warm to room temperature, then slowly heated to reflux, and maintained under reflux for 6-8 h. After cooling to room temperature, the excess pyridine was neutralized with 5% hydrochloric... 

The substituted 1,2,3-triol 1151 reacts with triphosgene in the presence of pyridine (Method A) to afford five-membered 1,2-cycUc carbonate 1152 as the sole product. However, reaction of 1,2,3-triol 1151 with dimethyl carbonate (Method B) affords the more stable internal cyclic carbonate 1153. 

Typical procedure. (2S,3S)-4-Benzyloxy-l,2,3-butanetriol 1,2-cyclic carbonate 1152 (Method A) [812] To a stirred solution of triphosgene (104 mg, 0.35 mmol) in di-chloromethane (1 mL) at —70 °C were added pyridine (0.29 mL, 3.59 mmol) and a solution of triol 1151 (125 mg, 0.59 mmol) in dichloromethane (1 mL). Once the addition was complete, the reaction mixture was allowed to warm to room temperature. The resultant homogeneous solution was quenched with saturated aq. ammonium chloride solution, washed with 1 n aq. HCl, saturated aq. NaHCOs, and brine, and dried over anhydrous MgS04. The organic layer was filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using EtOAc/hexanes (1 1) as eluent to afford (2S,3S)-4-benzyloxy-1,2,3-butanetriol 1,2-cyclic carbonate 1152 (108 mg,... 

Benzyl alcohol does not react with triphosgene at the low temperatures used in the above example in the absence of a base. On reacting benzyl alcohol with triphosgene at room temperature in the presence of pyridine, only benzyl chloride is isolated. Chloroformate 1 is formed initially, and if the alcohol is activated, as in the case of benzyl alcohol, decomposition ensues under these conditions, generating benzyl chloride in 90% yield [5]. (If the alcohol is not activated, decomposition will not occur.) Optimizations aimed at achieving higher yields of chloroformate 1 from the reaction of benzyl alcohol with triphosgene without a base led to a maximum of 15% of 1 besides 2 [4]. 

Compound 3.5a (5.0 g, 16.3 mmol) was dissolved in dichloromethane (150 mL) under nitrogen protection. Pyridine (30 mL) and the solid triphosgene gas (4.8 g, 16.3 mmol) were added at —40 °C. The reaction was stirred at 0 °C for 15 min. TLC showed that the reaction was completed. Saturated sodium bicarbonate solution (30 mL) was slowly added at 0 °C to quench the reaction. The reaction system was hltered, diluted with dichloromethane (100 mL), and washed with saturated sodium bicarbonate (3 x 50 mL), and the aqueous phase was extracted with dichloromethane (100 mL). The combined organic phases were dried over Na2S04 and then hltered. The solvent was removed by rotary evaporator, the resulting crude product was purihed by hash silica gel column chromatography (EA/HA = 1 5). 4.8 g white solid product was obtained (R/= 0.7, EA/HA = 1 2), yield 88 %. 

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