One-Pot Synthesis of Ureas from Boc-Protected Amines

Abstract

A practical one-pot synthesis of ureas is described. Boc-protected amines can be transformed into nonsymmetrical and symmetrical disubstituted and trisubstituted ureas utilizing 2-chloropyridine and trifluoromethanesulfonyl anhydride for the in situ generation of an isocyanate, which reacts with an amine. A variety of amines can be employed successfully, leading to high yields of isolated ureas.

Synthesis of Nitrogen‐Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells

“…One-pot reactions for the synthesis of amides and ureas directly from N-Boc-protected lactone 17 were also investigated in order to avoid the isolation of 8. [34,35] Unfortunately,b oth attempts led to product decomposition, and we rationalized that the chemical instability of 8 is due to the strong electron-donor effect of the para-amino group, whichp romotes ring opening of the dihydropyran-2-one moiety.…”

“…Although the structure of the product was confirmed by 1 H NMR spectroscopy, it turned into a black oil within a few minutes, indicating that p ‐aminogoniothalamin ( 8 ) is an unstable compound. One‐pot reactions for the synthesis of amides and ureas directly from N ‐Boc‐protected lactone 17 were also investigated in order to avoid the isolation of 8 . Unfortunately, both attempts led to product decomposition, and we rationalized that the chemical instability of 8 is due to the strong electron‐donor effect of the para ‐amino group, which promotes ring opening of the dihydropyran‐2‐one moiety.…”

A folding decalin tetra-urea for transmembrane anion transport

“…Spyropoulos and Kokotos recently published a convenient isocyanate synthesis involving treatment of a Boc-protected amine with triflic anhydride and 2-chloropyridine in DCM. 23 This method could be successfully applied to our decalin scaffold 15. After formation of the bis-isocyanate 16 was complete, as indicated by TLC, the resulting solution was added to an excess of amine 8 in pyridine.…”

A Reversible Single-Crystal to Single-Crystal Thermal Phase Transformation of 3-(2-Bromo-4-(1-methylethyl)phenyl)-1,1-dimethyl urea

“…Various efficient procedures have been used for the synthesis of ureas [5][6][7][8][9][10][11][12][13][14]. The most recent examples involve reactions of primary amines with S,S-dimethyl dithiocarbonate in water followed by reactions with secondary amines [15]; reactions of aromatic amines with secondary amines in the presence of carbon monoxide, sulfur and oxygen in dimethylformamide [16]; and reactions of benzylamine with secondary amines in the presence of a ruthenium catalyst [17].…”