With Urea or Isocyanates and Their Sulfur Analogs

With Urea or Isocyanates and Their Sulfur Analogs 

In 1872, Griess fused urea and 2-aminobenzoic acid and, although unaware of the nature of his product, had made quinazoline-2,4-dione. Since that time, the reaction has been frequently used for converting C-substituted 2-aminobenzoic acids to their corresponding quinazoline-2,4-diones in excellent yields, usually at 190°-200°C maintained for 1-5 hr.307,308 In addition, 2-aminopyridine-3-carboxylic acid and urea, slowly heated to 210°C, gave a good yield of pyrido[2,3-rf]pyrimidine-2,4-dione.286 Pyrido-[3,4-d]pyrimidine-2,4-dione was formed similarly (yield not given).288 

A simple, but seldom electronically favored approach is to boil the aminobenzoic acid and urea in water for a day this gave for the 5-nitro 

Thiourea, although a successful reagent for the o-aminoamides, has yet to establish itself in the o-amino acid series. Of the few known examples of its use, 2-aminobenzoic acid and thiourea at 170°C gave 2-thioxoqui-nazolin-4-one,310 and IV-phenylthiourea produced the 3-phenyl derivative311 in unstated (but apparently low) yields. Again, 2-aminopyridine-3-carboxylic acid and thiourea, at 210°C for only 5 min, gave a low yield of 2-thioxo-pyrido[2,3-d]pyrimidin-4-one (see 3).286 

Sodium and potassium cyanates, provided that attention is paid to their short shelf life (Section VII, A,6), offer an attractive alternative to fusion with urea for preparing annelated pyrimidine-2,4-diones. In the Organic Syntheses preparation of quinazoline-2,4-dione, anthranilic acid and potassium cyanate in cold dilute acetic acid were converted (in 20 min) to 2-ureidobenzoic acid, which cold aqueous sodium hydroxide cyclized to the quinazolinedione in excellent overall yield.312 Alternatively, the ring of a ureidobenzoic acid may be closed with hot, dilute hydrochloric acid.257 Ring closure of similar ureides in the pyridine series has required heating at 210°-240°C, often for as long as 3 hr.249,267 An even more Jt-deficient example, 2-aminopyrazine-3-carboxylic acid, did not react with sodium cyanate in dilute acid or with boiling urethane.127 

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