Efficient Synthesis of Ureas by Direct Palladium-Catalyzed Oxidative Carbonylation of Amines

Abstract

A general synthesis of symmetrically disubstituted ureas and trisubstituted ureas by direct Pd-catalyzed oxidative carbonylation of primary amines or of a mixture of a primary and a secondary amine, respectively, with unprecedented catalytic efficiencies for this kind of process, is reported. Reactions are carried out at 90-100 degrees C in DME as the solvent in the presence of PdI(2) in conjunction with an excess of KI as the catalytic system and under 20 atm of a 4:1 mixture of CO and air. In some cases, working in the presence of an excess of CO(2) (40 atm) in addition to CO and air (60 atm total) had a beneficial effect on substrate reactivity and product yield. Cyclic five-membered and six-membered ureas were easily formed from primary diamines. The methodology has been successfully applied to the synthesis of pharmacologically active ureas, such as those deriving from alpha-amino esters or urea NPY5RA-972, a potent antagonist of the neuropeptide Y5 receptor.

Carbon dioxide uptake as ammonia and amine carbamates and their efficient conversion into urea and 1,3-disubstituted ureas

“…The 1,3-disubstituted ureas are valuable products with a wide range of application as intermediates in agrochemical, pharmaceutical, dye chemicals and recently as precursors of isocyanates and raw materials of polyurethanes [29][30][31][32][33][34]. Their traditional synthesis required unsafe chemicals such as phosgene or carbon oxide and Au or Pt catalysts [35][36][37][38].…”

Synthesis of symmetrical 1,3-diarylureas by sulfur-catalyzed carbonylation in ionic liquids

“…On the other hand, the type of cations and anions of the ionic liquids also have a strong impact on the formation of DPU. With BMIm + as cation, the effect of anions, e.g., BF 4 − , PF 6 − , Cl − , on the carbonylation was examined (Table 1, entries 2, 3,9). Higher yield of DPU was achieved in BMImBF 4 .…”

“…Many strategies for nonphosgene routes including reductive carbonylation [2] and oxidative carbonylation [3] catalyzed by expensive transition metals such as Ru, Rh and Pd have been extensively studied. Furthermore, main-group elements such as selenium [4,5] or sulfur [6][7][8] have also been reported to catalyze these reactions.…”

ZrOCl2.8H2O: An Efficient Catalyst for the Synthesis of N,N?-Disubstituted Ureas from Biuret Under Solvent Free Conditions

“…Several urea derivatives are used as plant growth regulators, herbicides, pesticides, corrosion inhibitors, antioxidant, dyes for cellulose fibers, antidiabetic and tranquillizing drugs [12][13][14] . A large number of methods are reported for the synthesis of urea derivatives including oxidative 15 and reductive carbonylation 16 of amines, reaction of amines with phosgene and its derivatives 11,17 , carbmates 18 , isocynates 19 , or by reaction of urea or thiourea with amines 20 . Different catalytic systems are also reported for synthesis of urea derivatives such as iodine 21 , zinc chloride 22 , Cs 2 CO 3 23 , titanium (IV)isopropoxide and sodium borohydride 24 , CeCl 3 .7H 2 O-KI 25 , PEG-400 26 and zeolite HSZ-360 14 .…”