Diphosgene synthesis

Although the synthesis of the oxazolidinone 159 appeared to be well established, the scale-up of the reaction gave poorly reproducible results. The synthesis was much more efficient using diphosgene and a catalytic amount of activated charcoal <06S885>. 

The convenient synthesis of dichloroquinazolines 52 from anthranilonitriles by reaction with diphosgene was also applied to fusion of pyrimidine rings onto other heterocyclic aminonitriles <06SL65>. 

R Katakai, Y Iizuka. An improved rapid method for the synthesis of N-carboxy a-amino acid anhydrides using trichloromethyl chloroformate. (diphosgene). J Org Chem 50, 715, 1985. 

Homopolycarbonates based on 1 and 2 have been prepared by several groups. The interfacial polycondensation typical for the synthesis of aromatic polycarbonates is not useful with alditols, including 1, because they are water-soluble and less acidic than diphenols. The 1-based homopolycarbonate was prepared by phosgena-tion of the sugar diol, with phosgene or diphosgene in pyridine-containing solvent mixtures at low temperatures. The polycondensation of the isosorbide bischloro-formate in pyridine is an alternative approach. 

The regiolsomeric system (II) derived from the readily available 3-amino-2-pyridone is less easy to prepare. Cuillaumet and coworkers reported the synthesis of (II) via a one-step process using diphosgene (Ref. 239). The reaction was carried out in CH2CI2/THF mixture in presence of triethyl amine at-78°C, and the product isolated and purified by flash chromatography [Scheme 187]. 

Diphosgene has been widely used as a substitute compound for phosgene in different chemical synthesis... 

Sigurdsson et al. developed the synthesis of isocyanates from aliphatic amines [21]. Thus, the reaction of an aliphatic amine with trichloromethyl chloroformate (diphosgene) in the presence of Proton Sponge (1) (2 equiv.) at 0°C gave isocyanate in 81% yield. Azide isocyanate was synthesized from azide amine by means of a similar procedure by Keyes et al. [22] (Scheme 8.8). 

Diisocyanates are usually synthesized by phosgenation of the corresponding diamines. A tabulation of diisocyanates synthesized up to 1972 with pertinent methods of synthesis is available (11). Instead of the toxic phosgene gas, the liquid trichloromethyl chloroformate (diphosgene) (12) or the solid bistrichloromethyl carbonate (triphosgene) (13) can be used in the laboratory (see PHOSGENE). Also, oligomeric t-butylcarbonates are used to convert diamines into diisocyanates (14). 

Kurita systematically investigated the reactivity of diphosgene and compared its reactions with those of phosgene [52]. Ugi proposed diphosgene as the reagent of choice for the synthesis of isocyanides [53]. 

For the synthesis of 1,6-diisocyanatohexane, the amounts of both diphosgene and l,8-bis(dimethylamino)naphthalene were doubled. Hexamethylene diisocyanate... 

An interesting cydocarbonylation with diphosgene involving a thiourea-type sulfur atom has been reported in relation to a synthesis of condensed pyridazine derivatives, which are used as herbicides [795]. 

Typical procedure for the synthesis of t-valine N-carboxyanhydride, (2S)-4-isopropyl-oxazolidine-2,S-dione 1205 [887, 890] L-Valine (12.9 g, 0.11 mol) and activated charcoal (0.5 g) were suspended in anhydrous THF (100 mL), and to the suspension was added diphosgene (10.0 mL, 0.083 mol). The temperature was gradually increased to 60 °C, and the mixture was maintained at this temperature for 1 h. Excess phosgene was then removed by purging with nitrogen and the suspension was filtered through Celite. The yellow filtrate was concentrated in vacuo (<40 °C). Addition of pentane (ca. 500 mL) gave crystals of L-valine NCA, which were recrystallized twice from diethyl ether/pentane (14.32 g, 91%). 

A procedure using trichloromethyl chloroformate (diphosgene) has been successfully applied in the synthesis of isocyanato acid chlorides and isocyanato chloroformates from amino acids and amino alcohols, respectively [161,1016]. 

An interesting chiral building block for the synthesis of optically active unusual amino-hydroxy acids is (+)-8-phenylmenthyl isocyanoacetate 1532 [1170]. It is prepared in optically pure form in 95% yield by dehydration of the corresponding formamide with diphosgene within ca. 10 h at room temperature. 

High purity triphenylphosphine, as required in the Wittig ylide synthesis of al-kenes such as vitamin A, is prepared by the reaction of triphenylphosphine dichloride Ph3PCl2 with Mg, 7U, and/or Fe in the presence of an inert solvent. The Ph3PCl2 content of phosgene, chlorine, diphosgene, HCl, thionyl chloride, sulfuryl chloride, phosphorus trichloride and/or aliphatic halogen compounds (active chlorine compounds) must total less than 1000 ppm of free chlorine [1313]. 

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