DERIVATIVES OF FLUORENE. I. N-SUBSTITUTED 2-AMINOFLUORENE AND 2-AMINOFLUORENONE¹

Abstract

Interest in 2-aminofluorene and some of its derivatives in cancer research, hope of finding biologically interesting new substances, and curiosity about certain new or little explored series of fluorene compounds, led us first to attempt a better preparation of some simple derivatives which, even when available commercially, are sometimes in a state of purity which is belied by their cost. We can report a significant increase in yield with improvements in e& ciency and convenience for several known compounds as indicated in the experimental section.The derivatives discussed below are either new or were prepared by a better or more convenient method than so far reported.Since triethylphosphate2 is an outstanding dialkylating (1) and good monoalkylating agent for certain primary aromatic amines, we tried its action on 2-aminofluorene. A ratio of 3 moles of amine to 2 of the phosphate gave a high yield of 2-N , N-diethylaminofluorene. Extraction of the reaction mixture and use of acetic anhydride were not required. A final fraction, representing a 2 % yield, was found to be 2-N-ethylaminofluorene (2). Dialkyl alkylphosphonates apparently have not been used as alkylating agents for aromatic amines. Diethyl ethylph~sphonate~ was reacted with 2-aminofluorene (one mole pf amine to two of the phosphonate), with a quantitative crude yield, giving 98% of pure product. No trace of monoalkylated compound was detected.The yield of 2-K, N-dimethylaminofluorene has been reported from 22 % (crude yield with dimethyl sulfate alone) (3) to about 92% by way of the trimethylammonium iodide compound (4). The highest yield obtained with use of dimethyl sulfate was 50-60 % (5). Our results with triethyl phosphate suggested use of trimethyl phosphate in a similar reaction. Convenience and yield recommend this as the best preparative method.N-2-Fluorenyl-p-toluenesulfonamide (6, 7) was methylated with dimethyl sulfate. Attempts to hydrolyze the tosyl group with concentrated sulfuric acid, successful with some other derivatives of aminofluorene (6) resulted in a product, apparently 2-N-methylaminofluorene-~-sulfonic acid, isolated as the methyl ester.2-N-Methylaminofluorenone was made from 2-aminofluorenone in a 94 % over-all yield, by way of the N-p-tosyl and N-methyl-N-p-tosyl derivatives.

Effects of Molecular Structure and Hydrogen Bonding on the Radiationless Deactivation of Singlet Excited Fluorenone Derivatives

“…2-Methoxy- 21 and 2-COOCH 3 -fluorenone 22 were synthesized as reported in the literature. 2-((Trifluoroacetyl)amino)fluorenone was prepared from 2-aminofluorenone with trifluoroacetic anhydride . These fluorenone derivatives were purified by recrystallization and chromatography.…”

“…2-((Trifluoroacetyl)amino)fluorenone was prepared from 2-aminofluorenone with trifluoroacetic anhydride. 23 12 was kindly provided by Dr. Tomoyuki Yatsuhashi (present address: Dept. of Chemistry, Osaka City University, Osaka, Japan).…”

Discovery, synthesis and structure–activity analysis of symmetrical 2,7-disubstituted fluorenones as urea transporter inhibitors

“…Treatment of 2 with trifluoroacetic acid and heating to reflux in a sealed tube afforded trifluoroacetamide 7 . 24 The carbamate analog 8 was synthesized by reaction of 2 with potassium isocyanate. 25 Sulfonamide analog 9 was prepared by mesylation in pyridine.…”