196 McCONNAN : DIYALICYLAMIDE. XX. -Disalic ylamide. By JAMES 31CCONNAN. DISALICYLAblIDE (1EfO*C,,H,*CO'NHgCO*C,H4*OH) was first obtained by Schulerud (J. pi.. Chem., lSS0, [ii], 22, 289) by the action of hydrogen chloride on heated salicylamide. Subsequently G. Cohn (.I pr. Chem., 1900, [ii], 61, 552) found that disalicylamide is formed when salol and salicylamide are heated together at 215-220' ; at the same time he appears to have obtained n second compound which wa Y formulated as 0-salicylsalicylamide, C,H,(CO*NH2)*O*CO*C,jH4*OH, the properties of which were, however, practically identical with those of disalicylamide (Pntentschift, No. 11 I ,65 6). These two compounds are recorded in Beilstein's Handbuch (Erganxungsbaiad II., 892, 893), but the author, from previous work on acyl derivatives of salicylamide (Trans., 1906, 89, 1318), was led t o doubt Cohn's conclusions as t o the supposed 0-salicylsalicylamide.The properties assigned to the latter by Cohn were inconsistent with the 0-salicyl formula, as was also its mode of formation from salol and salicylamide, inasmuch as ammonia is evolved in the reaction ; it is now known that 0-acyl derivatives of salicylamide are instantly rearranged t o the corresponding N-acyl derivatives by ammonia. The reaction between salol and salicylamide has been repeated with the object of investigating this point, and it has been proved that 0-salicylsalicylamide is not formed. Two compounds are produced, namely : (1) Disalicylamide : HO*C,H,*CO*NH*CO*C,H4*OH, m. p. 203".McCONNAN : DISALICPLAMIDE. 197 (2) Polysalicylnitrile, m.11. 29 7" (Limpricht, A?male)z, 1856, 98, 261, &c.). The proportions of eash vary, and the amount of polysalicylnitrile formed increases rapidly with the proportion of salicylamide used. 0-Salicylsalicylamide has been obtained, however, by the rearrange- ment of disalicylamide by boiling with glacial acetic acid, the change taking place, according to the author's view, through an intermediate cyclic form : ,COON H* CO *C',H,*OH -+ $IO*NH C,H,*OH -+ C6H4<OK f- C,H,-O >"<OH t- GO-NH, CGH4<O*CO*C6H4*OH (compxe rearrangement of AT-benzoylsalicylamide, McConnan and Titherley,-Trans., 1906, 89, 132 1 ). 0-Salicylsalicjlamide undergoes the reverse change into disalicyl- amide on meltiug, on boiling with water, on standing in pyridine solution, or on treatment with alkaline reagents ; the two compounds are, in fact, in every respect andogous to the two benzoyl and the two acetyl salicylamides already described (106.cii., and Titherleg and Hicks, Trans., 1905, 87, 1207). The study of di:alicylamide has led t o the detection of an error in the recent work on acyl derivatives of salicylsmide (hlcconnan and Titherley, Trans., 1906, 89, 1326); it mas stated that the action of benzoyl chloride on a pyridine solution of Gerhardt's benzoyl salicyl- ainide a t - 15" led to the formation of two compounds : ( 1 ) O-A'-Dibenzoylsalicylamide : C,iH4<~~~NHGZ (m. p. 12S"). ( 2 ) 2 : '2-Phenyl-0-beiizoyl hydroxybenzometoxazone : All subsequent attempts to prepare the second compound in the same way failed, and i t has been shown that the formation of the derivative melting at 160" was due to the unsuspected presence of disalicylamide as impurity in the benzoylsalicylamide used.* It has been found t h a t the compound melting at 160' is easily obtained by pyridine benzoylation of disalicylamide, and that it is dibonzoyldi- salicylarnide : CsH,<2Bz CO-NH- BzO>CGH4.CO The view taken by lSlcConnan and Titherley of the tautomeric character of Gerhardt's benzoylsalicylamide is thus deprived of one * The con litions for the Iiroduction of disslicylainide :ire piesent in Gerhnrdt's method of preparing L~iizoylj'~licylaiiicle, siiicc the iiie thod iuvolves heating sitlicyl- aniide iu pieseiice of hycirocl~loric acid.198 McCONNAN : DISALICYLAMIDE.point of evidence previously adduced in it.s support ; this view, how- ever, has since been confirmed by new experimental evidence t o be published shortly. E s P E R I hi E N T A L. 42.8 Grams of salol (1 mol.) were heated with 41.1 granis of salicyl- amicle (18 rnols.) for two hours at 220°, the phenol forrnecl by the reaction being allowed to distil off. The product was poured into 100 C.C. of alcohol, and the resulting yellow precipitate, consisting of a mixture of disalicylamicle and polysalicylnitrile, W R S separated. The mixture was boiled for three hours with 300 C.C. of glacial acetic acid, when the disalicylainide completely dissolved, being a t the same time partly rearranged to 0-salicylsalicylamicle. The insolubie polynitrile was filtered from the Lot solution and naslied with acetic acid and water ; i t weighed 4 grams and melted a t 297".The hot acetic acid solution, on cooling and diluting with water, deposited 20 grams of a mixture of diealicylarnicle and 0-salicylsalicgl- amide ; these were separated from the clry mixture by extracting with boiling benzene, in which disnlicyla,mide is insoluble. 0-Salicylsalicyl- amide crystallised in a pure state fiom the hot benzene filtrate; it was filtered and washed with light petr oleuin. 0.2442 gave 11.7 C.C. nitrogen at 21" and 772 mm. o-X(~lic?/lsaZicylccr~~~~e melts a t 15'io, but solidifies in the course of a few seconds owing to rear1 angemenb t o disalicylarnide, which then melts at 200'. It is readily soluble in alcohol or hot benzene, moderately so in ether, sparingly so in light petroleum or cold benzene ; it crystallises from benzene iu colourless plates. I t s alcoholic solution gives with aqueous ferric chloride an intense red colour, which changes to violet on diluting with water.0-Salicy lsalicylamide is quantita- tively rearranged t o disalicylarnide on boiling p i t h water. It is readily soluble in pyridine, and the solution gradually acquires a yellvw colour owing t o the formation of disalicylamide, and the rearrangement is complete in six days. Aqueous alkalis dissolve it rapidly, yielding a yellow solution from which disalicylamide is precipitated on acidify- i n g ; in the case of sodium hydroxide, the sparingly soluble orange salt of disalicylainide is first formed and dissolves on dilution, O-Salicylsalicylaruide is rapidly decomposed by cold, strong sulphuric acid into salicylamide and salicylic acid (compare behaviour of its isomericle with strong sulphuric acid).I t s constitution follows from the close similarity between i t s properties and those of o-benzoylsalicyl- amide (Zoc. c'it.). N=5.54-. C',,H,,O,N requires K = 5.45 per cent.ABSORPTION SPECTRA AND OPTICAL ROTATORY POWER. 199 Disdicykamide, C,H,<OH CO*NH*CO>, HO 4. Disalicylamids was prepared by boiling finely-powdered 0-s Jicyl- salicylamide with fifty times its weight of water for fifteen minutes, when it was obtained as a very bulky, white, fibrous mass melting at 200' ; this crystallised from alcohol in yellow needles melting at 203', the properties of which agree in all respects with those ascribed to disalicylarnide by Schulerud and by G.Colin (Zoc. cit.). Disalicylamide is sparingly soluble in hot glacial acetic acid, but prolonged boiling converts it into the readily soluble O-salicylsalicyl- amide. One gram of disalicylamide was completely dissolved by 1 0 grams of acetic acid after thirty minutes' boiling; the mixture of the isomerides obtained by cooling and precipitating with water contained 66 per cent. of 0-salicylsalicylsmide. Disalicylamide is dissollred without change by cold, strong, sulphuric acid; it is decomposed into salicylainide and salicylic acid by heating it with strong aqueous ammonia in a sealed tribe at 115' for four hours. Dibenxoylclisa Zicylamide, <CO*NH.CO>, 4, is obtained in 4 O*Bz Bz-0 70 per cent. yield by pyritiine benzoylation of disalicylamide at - 15'. 0 2608 gave 7.0 C.C. nitrogen at 23" and 770 mm. N = 3.07. 0.3006 ,, 8.0 ,, ,, 20' ,, 771 mm. N=3.09. C,,H,,O,N requires N = 3:Ol per cent. The description of this compound already given (Zoc. cit.) must be amended in so far as it yields disalicylamide on decompositiotl by sul- phuric acid or sodium hydroxide. ORGANIC LABORATORY, UNIVEIWTY OF L r v e ~ ~ o o ~ .