Thiophosphoryl chloride synthesis

Thiotraamidophosphoric acids (35) are isoelectronic with phosphoric acids and were initially reported from the reaction of phosphorus pentasulfide with primary amines at high temperatures.62 Subsequently, an improved synthesis for 35 with increased yields and milder conditions has been reported involving the room temperature reaction of thiophosphoryl chloride and primary amines (Equation 50).63 The most convenient route to the analogous selenium derivatives SeP(NHPh)3 is from the oxidation of P(NHPh)3 with elemental selenium (Equation 51).63 Also isoelectronic with phosphoric acids are dithio wamido-phosphoric acids (36), which can be prepared from the reaction of phosphorus pentasulfide with an excess of primary amine at 30°C in toluene (Equation 52).62 The selenium derivatives of 36 can be prepared in a similar reaction from phosphorus (V) selenide, although due to their increased acidity... 

Following phosphorylation using the Yoshikawa procedure, the reaction of pyrophosphate with the intermediate phosphorodichloridate followed by aqueous work-up provides a convenient one-pot synthesis for triphosphates. With slight modification to this procedure, thiophosphoryl chloride can be used in place of phosphoryl chloride to give 5 -( 1 -thio)triphosphates as a mixture of two diaste-reoisomers (.S p and Rp). Both procedures require the prior preparation of the DMF-soluble, bis(tri-n-butylammonium) salt of pyrophosphate. This is prepared as a 0.5 M solution, can be stored in the fridge and is converted to its terrafcis(tri-n-butylammonium) salt immediately prior to reaction. Rates of nucleoside phosphorylation vary considerably and it is necessary to monitor the formation of the phosphorodichloridate during the Yoshikawa procedure in order... 

Simple modification of the Yoshikawa phosphorylation allows the synthesis of (1-thio) triphosphates (a-thiotriphosphates) (Protocol 12). The initial phosphorylation with thiophosphoryl chloride is slower than that using phosphoryl chloride and requires the addition of 2,4,6-collidine as a catalyst for the pyrimidine nucleosides.7 Protocol 12 is intended for pyrimidine nucleosides on a 0.2 mmol scale and should be modified where indicated for purine nucleosides. The diaste-reoisomers of nucleoside (l-thio)triphosphates can be distinguished by both 31P NMR (the signal for the a-phosphate of the Sp diastereoisomer is down-field relative to that of the Rp diastereoisomer) and reversed-phase HPLC (the Sp diastereoisomer elutes first). Preparative separation can also be achieved using the latter method (see Protocols 21-23).17... 

A facile one-pot synthesis of thiophosphoryl xanthates was carried out by using a mild base DBU-catalysed sequential reaction of excess alcohols with carbon disulfide and diethoxy thiophosphoryl chloride. ... 

Reaction of a nucleoside with thiophosphoryl chloride, followed by base-promoted cyclization, provides a direct synthesis of nucleoside-3, 5 -cycllc phosphorothioates (both epimers at phosphorus). 125 Treatment of cyclic AMP with dlphenylphosphoiyl chloride produces the mixed anhydride, predominantly of Rp configuration (62), due to the greater basicity of the axial oxygen in the cAMP. The anhydride reacted with dimethylamine with inversion to give the cyclic phosphoramidate.i26 Activation of cAMP with POCI3 in (MeOlaPO, followed by treatment with an amine, also gave predominantly the Sp-phosphoramidate (63),127 and in the case of a protected cAMP, oxalyl chloride activation achieved a similar result. 128 The hydrolysis of... 

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