Iodine‐Promoted Oxidative Conversion of o‐Vinyl Diaryl Ketones into o‐Acetyl Diaryl Ketones, Synthesis of 1‐Methyl‐4‐arylphthalazines as Analogues of Podophyllotoxin

Abstract

A new method is described for the metal‐free oxidation of o‐vinyl diaryl ketones in the presence of molecular iodine or N‐iodosuccinimide to give o‐acetyl diaryl ketones. This transformation involves the initial formation of an iodohydrin, and the o‐carbonyl group of the iodohydrin participates in a subsequent rearrangement to give the o‐acetyl diaryl ketone. The presence and participation of ortho‐carbonyl group is necessary for successful conversion. The envisaged 1‐methyl‐4‐arylphthalazines were synthesized from these o‐acetyl diaryl ketones, and their antiproliferative activity on mammalian cell lines was studied.

Syntheses of 6,7‐Benzotropolone by Using Ring‐Closing Metathesis Variants Obviating a Strongly Acidic Hydrolysis Thereafter

“…Scheme 3 shows how we synthesized the RCM substrates 7 a, which is an α-methoxy-α-(phenylsulfanyl)ketone, and 7 b, which is an α,α-dichloroketone. Starting from the commercially available 3-hydroxyphtalide (11), the known Wittig methylidenation [17] and a succession of in-situ activation and hydroxylaminolysis led to the Weinreb amide 13 [18] differently than previously described [18] (Scheme 3). It served as our acylating agent for lithiated methoxymethyl phenyl sulfide [19] on the one hand and for lithiodichloromethane [20] on the other.…”

“…Method 1b: Basic hydrolysis of acetate 18: 5-Oxo-5H-benzo [7] annulen-6-yl acetate (18) was dissolved in THF and KOH (1 m) was added. The mixture was stirred for 20 min at room temperature and then acidified with HCl-sol.…”

A Palladium-Catalyzed 4CzIPN-Mediated Decarboxylative Acylation Reaction of O-Methyl Ketoximes with α-Keto Acids under Visible Light

“…To the solution of the 1,2-diacylbenzenes ( 5 or 6 ) (0.2 mmol) in ethanol (2 mL) was added hydrazine hydrate (1 mmol), and the resulting mixture was heated at reflux for 6 h under nitrogen. After cooling to room temperature, ethanol was removed under vacuum to give the crude product, which was purified by silica gel column chromatography (ethyl acetate, hexane and methanol) to give the phthalazines ( 7 or 8 ) [ 21 ].…”

Recent Advances in the Chemistry and Biology of Podophyllotoxins

“…As shown in Scheme , the reaction of compounds 201 – 203 , prepared from 2‐(bromomethylene)benzoic acid and 2‐bromobenzaldehydes, with ArMgBr gave o ‐vinyl diaryl ketones 204 a – e , 205 a – c and 206 b , c , which were then converted into o ‐acetyl diaryl ketones 207 a – e , 208 a – c and 209 b , c , respectively. Finally, target compounds 210 a – e , 211 a – c and 212 b , c were easily afforded by the reaction of the above o ‐acetyl diaryl ketones with hydrazine hydrate . Among all derivatives, compounds 210 d , 211 a , and 212 c exhibited potent inhibitory effects against KB‐3‐1 cancer cells, with IC 50 values of 6.0, 2.8, and 18 μg mL −1 , respectively.…”

“…(a) Ref. ; (b) NaH, DMF, (CH 2 O) n , 0 °C→r.t. ; (c) KMnO 4 , H 2 O, r.t., then SOCl 2 , CH 2 Cl 2 , 45 °C, then NH(OMe)Me⋅HCl, Et 3 N, 0 °C→r.t.…”