Thioureas reaction with Merrifield resin

Procedure for multicomponent reaction Polymer-bound thiouronium salt 111 was prepared under standard conditions [132] by reacting thiourea with Merrifield resin in DMF at 80 °C. Resin 111 (0.8 mmol was treated with ethyl cyanoacetate (8 mmol) and various substituted aromatic aldehydes (8 mmol) and K2CO3 (10 mmol) in DMF at 80 °C for 24 h, under shaking in an Advanced Chemtech (Advanced ChemTech, Inc., LouisviUe, KY,... 

Sulfur linkers play an important role in solid phase synthesis and a set of modern Unkers based on sulfur chemistry can be found in the Hterature (Figs. 14 and 15). The linkers can be synthesized following various synthetic routes. One possibility is the reaction of Merrifield resin with potassium thioacetate and subsequent reduction using LiBH4 to give the free thiol 393. Another way to get the desired thio resin starts from Merrifield resin and thiourea followed by treatment with -butylamine [109,269]. 

Isothioureas can be prepared on insoluble supports by S-alkylation or S-arylation of thioureas (Entry 7, Table 14.6). Further methods for the preparation of isothioureas on insoluble supports include the N-alkylation of polystyrene-bound, A/,/V -di(alkoxy-carbonyl)isothioureas with aliphatic alcohols by Mitsunobu reaction (Entry 7, Table 14.6) and the addition of thiols to resin-bound carbodiimides [7]. Resin-bound dithio-carbamates, which can easily be prepared from Merrifield resin, carbon disulfide, and amines [76], react with phosgene to yield chlorothioformamidines, which can be converted into isothioureas by treatment with amines (Entry 8, Table 14.6). The conversion of support-bound a-amino acids into thioureas can be accompanied by the release of thiohydantoins into solution (see Section 15.9). The rate of this cyclization depends, however, on the type of linker used and on the nucleophilicity of the intermediate thiourea. 

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