Acetone → 1,2-Dihydroquinoline

Participants

Reaction Steps

1,2-dihydroquinolines are key intermediates in the preparation of a number of steroid receptor modulating compounds, and are prepared by a multi-step route culminating in the treatment of an aniline with acetone and iodine at elevated temperatures in a process known as the Skraup reaction, as shown below. See R. H. F. Manske et al., Organic Reactions 7: 59-98 (1953), and W. R Vaughan, Org. Synth. Coll. Vol III, 329-332 (1955). ##STR1## Many 1,2-dihydroquinolines are themselves steroid receptor modulating compounds. See, for example, PCT Int'l Publ. No. WO 96/19458; U.S. Pat. No. 5,693,647. Application of the traditional Skraup reaction to the synthesis of many of these 1,2-dihydroquinolines is problematic in that large quantities of a number of tarry by-products are formed that must be removed prior to use in further synthetic transformations, and the yields are generally low (15-50%). For example, as shown in U.S. Pat. No. 5,693,647, treatment of a polycyclic aniline, such as the amino-chloro-benzocoumarin shown below, with acetone and iodine at 130-135° C. affords only an 18% yield of the corresponding 1,2-dihydroquinoline. Furthermore, purification is very difficult due to the aforementioned by-product formation. ##STR2##

Provenance & Evidence