Fluorenone-2-carboxylic acid

Submitted by George Rieveschl, Jr., and F. E. Ray. Checked by R. L. Shriner and Arne Langsjoen. 

The hot mixture is stirred into 9 1. of hot water in a 5-gal. crock. The suspension is agitated for 15 minutes and is then filtered on a 24-cm. Buchner funnel. The filter cake is washed with four 400-ml. portions of 2% sulfuric acid. The wet filter cake is transferred to a 2-1. beaker containing 700 ml. of a 5% solution of potassium hydroxide (Note 5). The mixture is stirred 

A relatively large flask is used so that the sodium dichromate may be added without the escape of much acetic acid vapor. 

2-Acetylfluorene melting at 124-126° has been found to give as good results as the pure compound of melting point 128-129°. The submitters report that the over-all yield from fluorene to fluorenone-2-carboxylic add can be improved by the use of the crude product of the acylation (m.p. 113-117°) without purification (p. 4). 

The acetic acid solution of 2-acetylfluorene is conveniently and safely heated to the maximum temperature attainable on the steam bath, and then small portions of sodium dichromate are added as the speed of the reaction permits. To prevent a violent reaction, not more than 10 g. of dichromate is added until the oxidation has begun (as indicated by the appearance of a green color). 

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Trinitro-9-fluorenone, 2,5,7-trinitro-9-fluorenone-4-carboxylic acid... 

Diaryl ketones, such as o-bromobenzophenone and fluorenone carboxylic acids," are reduced by HI and red phosphorus in acetic acid or propionic acid under reflux, giving o-bromophenylphenyl-methane and fluorene carboxylic acid in high yields. 

The first account of the indeno[2,l-a]fluorene core in the literature dates to 1939 when Weizmann investigated polycyclic structures and their potential carcinogenic properties [23]. Intramolecular Friedel-Crafts acylation of 3,6-diphenylphthalic anhydride (113) in refluxing CS2 afforded fluorenone carboxylic acid 114 (Scheme 33). Acid chloride formation and subsequent cyclization in concentrated sulfuric acid generated the parent indeno[2,l-a]fluorene dione 115 in 5% yield with respect to 113. This was reaffirmed by Deuschel in 1951 where 115 is obtained in 72% under the same conditions [26]. 

By analogy, thermal cyclization was described also for 6-nitro-2 -hydroxy-biphenyl-2-carboxylic acids, e.g. 14, obtained by other methods. The same product 15 was also formed from lactone 17, prepared by oxidation of fluorenone 16 (Scheme 2). If the reaction was performed in DMF, the corresponding dimethylamide was isolated (82KGS703, 86KGS852, 87KGS314, 89MI1). 

Fluorenone derived linker 17 prepared in two steps was coupled to aminomethyl-PS via DIPCDI [21]. Due to the presence of an electron-withdrawing carboxamide group, the release of carboxylic acids from this support requires strong acids, such as trifluoromethanesulfonic acid (TFMSA) (Scheme 1). Insertion of an oxygen adjacent to the biphenyl rings to the fluorenone scaffold provides xanthene 18 handle [22]. The oxygen is strategically located to decrease the acid concentration required... 

Fluorenone-l-carboxylic acid, see Fluoranthene Fonofos oxon, see Fonofos Formaldehyde, see Acetaldehyde, Acrolein,... 

Refluxing of 9-fluorenone-l-carboxylic acid with zinc dust and copper sulfate in aqueous potassium hydroxide for 2.5 hours afforded 9-fluorenol-1-carboxylic acid in 94% yield [1004]. Reduction with sodium borohydride in aqueous methanol at 0-25° converted 5-ketopiperidine-2-carboxylic acid to /ra j-5-hydroxypiperidine-2-carboxylic acid in 54-61% yield [1005], On the other hand, reduction of V-benzyloxycarbonyl-5-ketopiperidine-2-carboxylic acid gave 89% yield of V-benzyloxycarbonyl-cis-5-hydroxypiperidine-2-car-boxylic acid under the same conditions [1005],... 

The expedient and regioselective metalation of unprotected biphenyl-2-, -3-, and -4-carboxylic acids has been reported.59 Unprotected biphenyl-2-carboxylic acid has been cleanly metalated with. sex-butyllithium at the position adjacent to the carboxylate and can then be subjected to site-selective electrophilic substitution (Scheme 8). The remote C(2 )-position has been attacked by the superbasic mixture of n-BuLi and t-BuOK (LICKOR) in THF or benzene. The resulting dianion cyclizes to give the fluorenone skeleton. The mechanism of the metalation of homologous compounds, 2-(pyridin-3-yl)benzoic acid derivatives, with strong bases has also been discussed.60... 

The formation of a phenanthridine lactone by the persulfate oxidation of 2 -cyanobiphenyl-2-carboxylic acid is interesting in that little is known of the addition of radicals to the C=N system. The mechanism proposed below (Scheme 1) also accounts for the occurrence of fluorenone as a by-product.64... 

Unsuccessful attempts to obtain phenanthridone carboxylic acids by the Beckmann route have also been reported. The oxime of fluorenone-1-carboxylic acid (63) gave only the oxazinone (64) on... 

Hydrazoic acid attacks the carbonyl and carboxy groups of fluorenone-l-carboxylic acid simultaneously giving mainly 4-amino-phenanthridone together with some acidic material, presumably phenanthridone-4-carboxylic acid.89 The latter is best prepared by prior protection of the carboxy group with pyrrolidine.106 112 The increase in strain associated with the conversion of 4,5-dimethyl-fluorenone into 1,10-dimethylphenanthridone is reflected in the relatively low yield (50%) obtained under Schmidt conditions.22... 

Among the electron acceptors which exhibit the sensitization 133 are various nitro compounds, cyano-compounds, some organic acids such as phthalic acid, carboxylic acid anhydrides, quinones, etc. The most efficient electron accepting sensitizer known to date is 2,4,7-trinitro-9-fluorenone (TNF)134,135. Not surprisingly,... 

The formyloxy group of cis-8,9a-H-8-formyloxyperhydropyrido[2,l-c][l,4]-thiazin-4-one was hydrolyzed to a hydroxy group and the hydroxy group was oxidized to an oxo group with fluorenone in the presence of ferf-BuOK in benzene at ambient temperature (81EUP34015). 6-Oxoperhydropyrido[2,l-c][l,4]oxazine-4-carboxylic acid was obtained by hydrolysis of the ethyl ester in the presence of LiOH in aqueous THF at 0°C (96MIP8). An amide was prepared from 4-carboxylic acid. 

It has also been found that certain aldehydes, ketones and carboxylic acids esters form well defined products with nitric acid (Reddelien [5]). For example, bemzaldehyde with 60% nitric acid gives a colourless, unstable oil, and cinnamic aldehyde forms fairly stable white crystals, melting at 60-61°C, with 65% nitric acid. Acetophenone, benzophenone, fluorenone, phenanthrenoquinone and camphor give similar addition products. 

This crude 2-acetylfluorene is completely soluble in carbon disulfide and thus is free of the insoluble 2,7-diacetylfluorene. It may be used directly for the oxidation to fluorenone-2-carboxylic acid (p. 63). 

The method described is a modification of the method of Dzie-wonski and Schnayder and is described in a patent by the submitters. Fluorenone-2-carboxylic acid has also been obtained by the oxidation of 2-fluorenealdehyde. ... 

Prior to our work, fluorenones had been synthesized by methods characterized by the limited accessibility of the starting substrate [28,30,32,33] (substrate being fluorene, biphenyl-1-carboxylic acid, benzophenone, fluoranthene, cyclohexene, phenanthrene or phenylpropionic acid derivatives), a lack of stereoselectivity [28,29,31,33] and poor yields. We therefore developed a simple methodology for synthesizing fluoren-9-ones via domino acylation-cycloalkylation/alkylation-cycloacylation (Chart-19). 

Oxidative decarboxylation.1 Heating fluorene-9-carboxylic acid (I) with 2.0 molar eq. of basic copper carbonate affords fluorenone (2, 56% yield). This reaction is the first report of a direct oxidative decarboxylation with copper salt catalysis. 

Hydroxydiphenyl-2-carboxylic acid lactone. Baeyer-Villiger oxidation of 9-fluorenone to 2 -hydroxydiphenyl-2-carboxylic acid lactone is done conveniently in even large-scale runs1 by slow addition with cooling in acetone-dry ice of 55 ml. 

HDPE, 231J, control 925 HDPE + TiO2 (2.3%) 6U HDPE + anthraquinone 385 HDPE + anthrone 20 HDPE + benzanthrone 20 HDPE + 2-methylanthraquinone 50 HDPE + 1,3,5-triacetylbenzene 50 HDPE + a-bromo- -phenylacetophenone 75 HDPE + 9-fluorenone-U-carboxylic acid 575 HDPE + flavone 650... 

Oxidation, arylmethyl group to a carboxylic acid, with CrOj, 30 with KMnOi, 39, 219, 265 benzophenone hydrazone to diphenyl-diazomethane, 134 fluorene to fluorenone, 163 indene to homophthalic acid, 173 8-hydroxyquinoline to quinolinic acid, 266... 

Table 4.23 Preparation of fluorenone and related cyclic and heterocycles ketones via cycloacylation of the corresponding aryl carboxylic acids promoted by Nation...

The oxygen and 9-fluorenone-l-carboxylic acid quenching experiments on the photohydration of p-NDHD show that the triplet excited states are involved to give the primary photoproducts. The photohydration of p-NDHD exhibits a maximum efficiency at Hq = -1.0 for both primary photoproducts, as shown by the measurements of quantum yields as a function of acidity. The suggested mechanism involves a nucleophilic attack of water, synchronous with protona-... 

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