Triphosgene

Succinic anhydride can be prepared from succinic acid by dehydration it operates in high boiling solvent (31), in the presence of clays as a catalyst (32), or at room temperature with triphosgene (33). 

Triphosgene (bis(trichloromethyl)carbonate) has been used to deoxochlorinate [VOCh] - to [VClfi] - and [V02Cl2] to [VOCh] [6]. In both these cases the deox-ochlorination was accompanied by spontaneous reduction of the initial products (Scheme 6.1-2). 

Amino-3-phenyl-3,4-dihydro-2(177)-quinoxalinone (181) and triphosgene gave 4-phenyl-47/-imidazo[l,5,4-< e]quinoxaline-2,5(l//, 6//)-dione (182) (EtsN, THF, 20°C, N2, until substrate gone by tic 65%) analogs Ukewise. ... 

Treatment of a chiral amine with phosgene is the cheapest way to prepare symmetrical ureas [29]. Nevertheless, due to the toxicity and reactivity of that reagent, it can advantageously be replaced by triphosgene [30] or l,l -carbonyldiimidazole [31-34] or other derivatives such as l,l -carbonyldi-2(lH)-pyridinone [35]. This procedure can be extended to thiophosgene (Scheme 1) and its thio-analogues, such as l,l -thiocarbonyldi-2(lH)-pyridinone to produce thioureas [36] chiral diamines can thus be transformed into the corresponding monoureas or monothioureas. 

Silylation of amino acids such as r-leucine 180 with TCS 14 gives rise to the O-silylated ammonium salt 181, which reacts selectively with triphosgene and triethylamine to afford the isocyanate 182. Subsequent reaction of 182 with primary amines such as free r-leucine 180 or secondary amines such as N-BOC-pi-perazine 184 affords the ureas 183 and 185 in 49% or 77% overall yield, respectively [10] (Scheme 4.7). 

Materials and Purification. Chemicals were purchased from Aldrich chemical company and used as received unless otherwise noted 1,1,1,3,3,3-hexamethyl disilazane, ethylene glycol, triphosgene, poly(ethylene oxide) (MW = 600), poly(tetramethylene oxide) (MW = 1000), poly(caprolactonediol) (MW = 530), toluene diisocyanate (TDI), anhydrous ethanol (Barker Analyzed), L-lysine monohydride (Sigma) and methylene bis-4-phenyl isocyanate (MDI) (Kodak). Ethyl ether (Barker Analyzer), triethylamine and dimethyl acetamide were respectively dried with sodium, calcium hydride and barium oxide overnight, and then distilled. Thionyl chloride and diethylphosphite were distilled before use. 

Fluoro-4-hydroxy-17/-[l,2,4]triazino[4,5- ]quinoline-l,6(2//)-dione 72 was synthesized via the cyclization of the quinolinecarboxylic hydrazide 144 by triphosgene. The hydrazide intermediate 144 was obtained from the corresponding ester 143 (Scheme 16) <2003JHC789>. 

The general procedure used for the synthesis of [l,2,3]triazolo[l,2-tf][l,2,4]benzotriazin-l-5(6//)-dione derivatives 506 is shown in Scheme 86. Ionic 1,3-dipolar cycloaddition of the appropriate azide 503 to ethyl phenylacetates gives l-(2-nitrophenyl)-4-aryl-5-oxo[l,2,3]triazoles 504. Catalytic reduction of these compounds affords the corresponding amines 505. Cyclocondenzation of these amines to the final tricyclic compounds 506 is performed using triphosgene in anhydrous tetrahydrofuran solution at room temperature (Scheme 86) <2005JME2936>. 

Pyrimidin-2-ones 43 with fluorinated substituents have been prepared by reaction of metallated imines with fluorinated nitriles, followed by cyclisation with triphosgene <06T1444>. 

Pure triphosgene decomposes when heated above 266° F to produce three molecules of Phosgene (C10-A003). Impure material decomposes at lower temperatures. Moisture may accelerate decomposition to phosgene at normal temperatures. 

Damle, Suresh B. "Safe Handling of Diphosgene, Triphosgene." Chemical Engineering News 71 (8 Feb 1993) 4. 

When the mixture was refluxing, the triphosgene (5.81 g) was added carefully, portionwise over 5 minutes. The mixture was heated for 1 hour. 

Triphosgene is very toxic. Wear suitable gloves, and eye and face protection. Handle very carefully in a well-ventilated fume-hood. 

The mixture gradually became clearer as the insoluble material was consumed. If the mixture is not clear after 1 hour continue heating for another 20 minutes. If the mixture at this stage remained unclear, 0.53 g of triphosgene was added and heated further. 

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