Benzilic acids

The lDcii70in and nltiic acid are heated on the water-bath with an. ir condenser, the flask being occasionally shaken. Nitrous fumes arc evolved, and the crystals of benzoin are converted into a yellow oil, which, after two hours heating, is free from un-(hanged benzoin. The contents of the flask are now poured into water, and the yellow crystalline deposit separated by filtration, washed with water, and recrystallised fiom alcohol. Yield, 10—12 grams. 

Propa-tic .—Yellow prisms m. p. 95 insoluble in vater soluble in hot alcohol. 

Kcatf/o .—I. Dissolve a small quantity of benzil in a little alcohol, add a fragment of caustic potash and boil. A violet solution is obtained. 

Benzilic Acid, (CeHf,)2C(0H).C02H 10 grms. benzil. 

The caustic potash is melted with a small quantity of water in a siheror nickel crucible. The temperature of the mass is brought to 150, and the finely powdered benzil added. The benzil melts, and the mixture shortly changes to a solid mass of potassium ben/ilatc. The cooled melt is dissolved in water, and the alkaline solution acidified with hydrochloric acid, which precipitates the benzilic acid. The crystalline mass, which contains small quantities of benzoic acid, is separated from the mother-liquor and washed with cold water. It is then transferred to a porcelain basin, dissolved in hot water, and the solution boiled until the smell of bcn/oic acid has gone. On cooling, benzilic acid crystallises out, and is purified by a second crystallisation from hot water. 

Benzoyl chloride and benzoic anhydride, by heating with excess chlorosulfonic acid followed by addition of the crude reaction mixture to crushed ice, both afforded 3-chlorosulfonylbenzoic acid. These carboxylic acid derivatives (acid chlorides and anhydrides) are easily hydrolysed to the carboxylic acid group in the work-up procedure, so they behave similffl ly to the parent arylcarboxylic acid. On the other hand, arylcarboxylic acid esters may be chlorosulfonated without loss of the ester group thus methyl-1-naphthalenecarboxylate 297 by treatment with excess chlorosulfonic acid gave the corresponding 5-sulfonyl chloride 298 (Equation 92). Similar results were reported in the chlorosulfonation of ethyl chlorophenoxyacetates in which the ester grouping was retained. 

The most important reaction of benzil and related compounds is the benzilic acid rearrangement discovered by J. von Liebig. 

Experiment.1—Benzil (5 g.) is heated for ten minutes to boiling on the wateT bath with 15 c.c. of alcohol and a solution of 5 g. of potassium hydroxide in 10 c.c. of water. After cooling, the suspension of potassium benzilate crystals is filtered as dry as possible by suction, and the salt, after being washed with a little alcohol, is dissolved in 20-30 c.c. of cold water. The solution is filtered and dilute sulphuric acid is added, at the boiling point, to the clear filtrate. The free acid is precipitated partly in the form of crystals. It is separated by filtration with suction while hot and washed with hot water. It can then be recrystallised at once from a large volume of hot water or, after drying, from benzene. Yield about 4 g. 

The first stage of the rearrangement, which proceeds according to 

By a similar reaction phenanthraquinone yields biphenylene-glycollic acid. (The equation should be written.) The benzilic acid rearrangement also plays a part in many other reactions (croconic acid, purpurogallin). 

Here also formally OH exchanges its place with an alkyl radicle, CH3, although actually—since concentrated sulphuric acid is used— the elimination of water between the two OH-groups provokes the wandering of a methyl. group. 

Method 2. Prepare a solution of 50 g. of sodium hydroxide and 11 5 g, of sodium bromate (or 12 -5 g. of potassium bromate) in 90 ml. of water 

The benzil used must be pure, such as is obtained by recrystallization from alcohol. A number of experiments which were carried out with crude benzil which had merely been washed with water did not give nearly such good yields. 

If the potassium salt s not isolated but the reaction mixture is immediately acidified, there is mixed with the benzilic add a certain amount of benzoic add which is difficult to remove. This may be done either by fractional solution in sodium carbonate 1 (benzilic acid is a stronger acid than benzoic), by shaking with ligroin,2 which extracts the benzoic acid from the benzilic, or by boiling with water 3 for some time until the odor of benzoic acid has disappeared. It is better to isolate the potassium salt, since upon acidification very pure benzilic acid is obtained in spite of the fact that it is slightly colored. 

In the preparation of certain benzilic acid derivatives froir substituted benzils, it has been found that simply dissolving the substituted benzil in alcoholic alkali is sufficient to complete the conversion and no heating is required. With unsubstituted benzil, however, a much poorer yield of benzilic acid is obtained if the reaction mixture is not heated. Longer heating than that given in the directions is likely to decompose some of the product to benzoic acid. 

The amount of alcohol and the concentration is such that the maximum amount of potassium benzilate will crystallize out. 

If more alcohol is used in proportion to the water, a large amount of potassium salt crystallizes during the heating and this is objectionable, while less alcohol holds in solution a considerable amount of potassium benzilate and thus decreases the yield. 

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When benzii is heated with potassium hydroxide solution, it undergoes a molecular rearrangement with the formation of the potassium salt of benzilic acid, or diphenyl lycollic acid ... 

This reaction applies to many i,2 diketones, and is termed the Benzilic Acid Rearrangement. It provides a ready method for the preparation of disubstituted a4iydroxy-carboxylic acids. When applied to a cyclic 1,2-diketone, the ring system is necessarily reduced by one carbon atom for example, cyclohexan-i,2 ... 

To obtain the free acid, dissolve the potassium salt in 50 ml. of cold water, filter the solution if a small undissolved residue remains, and then boil the clear solution gently whilst dilute sulphuric acid is added until the separation of the acid is complete. Cool the solution and filter off the pale orange-coloured crystals of the benzilic acid wash the crystals on the filter with some hot distilled water, drain well, and then dry in a desiccator. Yield of crude acid, 4 g. Recrystallise from benzene (about 50 ml.) to which a small quantity of animal charcoal has been added, filtering the boiling solution through a preheated funnel fitted w ith a fluted filter-paper, as the benzilic acid readily crystallises as the solution cools alternatively, recrystallise from much hot water. The benzilic acid is obtained as colourless crystals, m.p. 150°. 

Benzil (and other a-diketones Ar—CO—CO—Ar) upon refluxing with aqueous-alcoholic potassium hydroxide undergo the beozilic acid rearrangement. Thus benzil is converted into a salt of benzilic acid ... 

Benzilic acid may be obtained in a high state of purity by the action of an alkaline bromate solution upon benzoin at 85-90° ... 

Diphenylacetlc acid. The reduction of benzilic acid with red phosphorus and a little iodine in 98 per cent, acetic acid solution yields diphenylacetlc acid ... 

Place 125 ml. of glacial acetic acid, 7 -5 g. of purifled red phosphorus (Section II,50,d) and 2 5 g. of iodine in a 500 ml, round-bottomed flask fitted with a reflux condenser. Allow the mixture to stand for 15-20 minutes with occasional shaking until aU the iodine has reacted, then add 2 5 ml. of water and 50 g, of benzilic acid (Section IV,127). Boil the mixture under reflux for 3 hours, and filter the hot mixture at the pump through a sintered glass funnel to remove the excess of red phosphorus. Pour the hot filtrate into a cold, weU-stirred solution of 12 g. of sodium bisulphite in 500 ml, of water the latter should be acid to litmus, pro duced, if necessary, by passing sulphur dioxide through the solution. This procedure removes the excess of iodine and precipitates the diphenyl-acetic acid as a fine white or pale yellow powder. Filter the solid with suction and dry in the air upon filter paper. The yield is 45 g., m.p. 

Benzilic acid melts at 149-150°, i.e., very close to that of diphenylacetic acid. The completeness of the reduction can easily be tested by treating a little of the product with concentrated sulphuric acid if even a trace of benzilic acid remains, the sulphuric acid will have a rod colour. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

As is not uncommon in homologous series, close homologues sometimes showed anomalous behaviour, e.g., of the benzilic acid esters with the following basic components —... 

The benzilic acid rearrangement of steroid a-diketones is often the preferred method for ring contraction. Yields are generally excellent, and in several instances the reaction has been shown to be stereospecific. Preparation of the starting a-diketones is discussed below and illustrated with several excellent experimental procedures. 

Hirschmann and co-workers have reported the synthesis of another A-nor analog of cortisone obtained from the benzilic acid rearrangement of a 2,3-diketo-A -steroid. 17a,20 20,21-Bismethylenedioxypregna-L4-diene-... 

In systems which preclude retro-aldol condensations, benzilic acid rearrangement of 11,12-diketones affords normal C-norsteroids in fair yields. For example, 11,12-diketotigogenin (82) is converted to the C-nor-(5oc,9(, 22a)-spirostane (83) in 65 % yield by barium oxide in boiling aqueous methyl-cellosolve. ... 

An interesting one-step combined oxidation and benzilic acid rearrangement has been described by Holden and Kerwin in connection with the synthesis of C-norpregnanes from 3a,20yS-dihydroxy-5j9-pregnan-12-one (partial structure 85). 

Ring contraction by benzilic acid rearrangement of a-diketones... 

Baeyer-Villager oxidation, 10, 151, 433 Bamford-Stevens reaction, 402 Barton reaction, 253 Beckmann rearrangement, 140 Benzilic acid rearrangement, 418, 435 3 -Benzoyloxy-7-methylenecholest-5-ene, 60 Benzylmagnesium chloride, 64 3-Benzyloxycholesta-3,5-diene, 342... 

Ri acHon.—Add a little concentrated sulphuiic acid to benzilic acid. It dissolves with an intense red colour. See Appendix ... 

The isolation in poor yield of 2,5,5-triphenyl-4(5f )-oxazolone (82) by reaction of benzilic acid with benzonitrile in concentrated sulfuric acid was claimed by Japp and Findlay. Cornforth, however, suggested that the reactions of this product, m.p. 136°, could be accounted for more satisfactorily by the isomeric 5(4i ) structure 83. 

The structure of 82 was established by alkaline ring cleavage to benzilic acid amide and by hydrogenolysis to (C6H5)2CH—CONH— COCfiHs. These reactions also served to eliminate 83 as the structure of the 169° compound. The other possible isomeric structure, (C6H5)2C(CN)0C0C6H5, which could have formed after 0-acylation, was ruled out by its independent synthesis from bromodiphenyl-acetonitrile and silver benzoate. 

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