2-Thioxo-4 -quinazolinones

N-3-Substituted 2-thioxo-4-quinazolinones 859 are formed when alkyl or aryl isothiocyanates are reacted with anthranilic acids or esters 857, <2001JME1710, 2002AP556, 2004JC0584, 2006JME2440>. The intermediate di-substituted thiourea 858 is normally not isolated, but is directly ring-closed in situ to the thioxoquinazolinone product 859. When 3-unsubstituted products are required, benzoyl isocyanate can be used <20008714>. 

Similar results can be achieved by using cyanothioformamides <2002HAC291, 2002HAC611> or dithiocarbamates 861 <2005BML1877> instead of isothiocyanates, as shown by the synthesis of 2-phenyl-2-thioxo-4-quinazolinone 863 <2005BML1877>. Once again the intermediate thiourea 862 is not isolated. 

When an anthranilic acid ester is heated with ammonium thiocyanate, 2-thioxo-4(3//)-quin-azolinones (629) are formed. When alkyl- or aryl-isothiocyanates are used, the corresponding N3-substituted 2-thioxo-4-quinazolinones (629) are formed . 

The 277,477-3-bromomethyl-3,4-dihydro-[l,3]thiazino[3,2- ]quinazolin-6-one 341 was formed from the 2-thioxo-quinazolinone 340 using Br2/AcOH (Equation 36) <2000S714>. 

Pyrazolopyrimidinones C NMR, 5, 308 methylation, 5, 310 synthesis, 5, 329 Pyrazolopyrimidinones, thioxo-synthesis, 5, 324 Pyrazoloquinazolines synthesis, 5, 317, 322 Pyrazolo[ 1,5-n]quinazolines synthesis, 5, 273 Pyrazolo[ 1,5-c]quinazolines synthesis, 5, 324 Pyrazolo[2,3-n]quinazolines synthesis, 3, 378 Pyrazoloquinazolinones synthesis, 5, 342 Pyrazolo[4,3-/]quinazolinones synthesis, 5, 273 Pyrazolo[4,3-g]quinazolinones synthesis, 5, 273 Pyrazolo[3,4-/]quinolines synthesis, 5, 273 Pyrazolo[4,3-/]quinolines synthesis, 5, 273 Pyrazolo[l,5-n]quinoxalines synthesis, 5, 339 Pyrazolo[3,4-6]quinoxalines synthesis, 5, 272... 

When the carbon dioxide is replaced with carbonyl sulfide, generated in situ from carbon monoxide and sulfur, 4-thioxo-2-quinazolinones 818 are produced <2000HAC428>. 

The reaction of 3-amino-2-thioxo-4(l//)-quinazolinone or its methylthio derivative 96 with hydrazonoyl halides 95, in the presence of ethanol and triethylamine afforded 6W-1,2,4,5-tetrazino[3,2-b]quinazolin-6-ones 97 <01M959>. 

Proquinazid can be prepared starting from 5-iodoanthranilic acid (Scheme 22.3) [27, 32, 33]. Cyclization with n-propyl isothiocyanate affords 2,3-dihydro-6-iodo-3-propyl-2-thioxo-4(lH)-quinazolinone. Alternatively, this key intermediate can be obtained by reaction of an appropriate anthranilate with thiophosgene and n-propylamine. Subsequent introduction of the propoxy substituent via a methyl-ation displacement sequence concludes the synthesis. 

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