Synthesis and structural elucidation of novel camphor‐derived thioureas

Abstract

Nine novel (+)-camphor-derived thioureas have been prepared. 3-((Dimethylamino)methylene)camphor (2) served as the common precursor for the preparation of both, 2-thiourea 15-20 and 3-thiourea functionalized camphor derivatives 6, 7/7', respectively. Starting from 2, the latter were prepared in two or three steps whereas the former in five steps, respectively. Configuration of all novel compounds has been meticulously determined using NMR techniques and/or single crystal X-ray crystallography.

Synthesis of 2‐(3‐(3,5‐bis(trifluoromethyl)phenyl)thioureido)‐3‐((dimethylamino)methyl)camphor organocatalysts

“…The title bifunctional camphor‐derived organocatalysts 7 , 8 , 9 were prepared in five steps starting from (+)‐camphor ( 1 ). Following the literature procedure, (+)‐camphor ( 1 ) was transformed into 3‐((dimethylamino)methylene)camphor ( 2 ). Next, catalytic hydrogenation of enaminone 2 in EtOH in the presence of 10% Pd–C and excess HCl gave the corresponding ammonium salt as a mixture of the major endo ‐epimer 3 and the minor exo ‐epimer 3 ’ in a ratio of 78:22 and in 100% conversion.…”

“…(+)‐Camphor ( 1 ), tert ‐butoxy bis(dimethylamino)methane, anhydrous DMF, 1‐isothiocyanato‐3,5‐bis(trifluoromethyl)benzene ( 6 ), p ‐toluidine hydrochloride ( 10 ), (1 S )‐(+)‐camphorquinone ( 16 ), dimethyl malonate ( 20 ), trans ‐β‐nitrostyrene ( 21 ), and 10% palladium on charcoal are commercially available (Sigma‐Aldrich, St. Louis, MO, USA). (1 S ,4 S ,3 E )‐3‐((Dimethylamino)methylene)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐one ( 2 ), (1 S ,4 R ,3 E )‐3‐(hydroxyimino)‐1,7,7‐trimethylbicyclo‐[2.2.1]heptan‐2‐one ( 17 ), and (1 S ,2 R ,3 R ,4 R )‐3‐amino‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐ol ( 18 ) were prepared following the literature procedure.…”

“…To a solution of (1 S ,4 S ,3 E )‐3‐((dimethylamino)methylene)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐one ( 2 ) (1.5 g, 7.24 mmol) in anhydrous EtOH (40 ml) under Argon, Pd–C (10%, 450 mg) and HCl (5 ml, 2 M in EtOAc, 10 mmol) were added. The reaction vessel was flushed with H 2 , and the reaction mixture was hydrogenated in a Paar hydrogenator (P = 4 Bar) at room temperature for 3 h. The reaction mixture was filtered through a plug of Celite® and washed with EtOH (100 ml).…”

Synthesis and Reduction of 10-Phthalimidocamphor Oxime

“…26 Amine 6 failed to catalyze the reaction (Scheme 4). The structures of novel compounds 3, 4, 6, and 7 were determined by spectroscopic methods ( 1 H-NMR, 13 C-NMR, IR, HRMS).…”

“…1,2 All of the above makes camphor a very desirable starting compound for the preparation of a wide variety of products 3 ranging from natural products 1,2 to chiral auxiliaries, 4,5 ligands in asymmetric synthesis, [6][7][8][9][10] organocatalysts, 11 and NMR shift reagents. 12 Within our continuing study on camphor-based diamines as potential organocatalyst scaffolds, [13][14][15] we recently reported on the synthesis of a novel type of 1,3-diamine-derived bifunctional squaramide orga nocatalysts A prepared from 10-iodocamphor and their application as highly efficient catalysts in Michael additions of 1,3-dicarbonyl nucleophiles to trans-β-nitrostyrenes. 16 10-Iodocamphor 17 has seen surprisingly limited appli cation as the starting compound, [18][19][20][21][22][23][24] although, it can easily be prepared in sufficient quantities from (1S)-(+)-10-camphorsulfonic acid.…”