110' for several hour5 mG-iphriq~horuspcntoxidc iiiit IL 1 reduced pressure An alcoholic solution of the product shows no coloration with ferric chloridc and it does not reduce Fehling'c solution. A chloroforni solution of the substance ab\orbs bromine and it shows a yellow coloration in acetic acid on the addition of a few drops of sulfuric acid. Thc product was recovered unchanged afteI refluxing with acetic anhydride and sodiuni acetate for two houri. 11 was not affected by cold 207, potassium hydroxide bui tin~olvedslowly on tmling : I ) pi odricc~:t light yellow iolii t 1011
Anal. Calcd for CZ~HZIO~(OCH&. (3, 7 2 7 , H . 6.27 OCHs, 20 1 , mol. wt , -162.1 Found: C,72 0 , 51, ii ii0 OCHI, 20 06; mol. wt (Past), 420, 437. The same product was obtained by application of thc same methylation procedure to pomiferin dimethyl ethei The identity of the products was established by melting point and mixed melting point. Absorption Spectra.'-The absorption spectra of osajin, ]so-osajin, pomiferin and iso-pomiferin were observed in absolute ethanol. The data are shown in Fig 2 and Fig 3. A single band qpectrum was obtained for each coni pound.
Acknowledgment is gratefully made to the National Youth Administration for assistance rendered in this investigation. Summary 1. A second yellow pigment has been isolated (7) The absorption spectra measurements uere made by Miss J Appleton of this Laboratory, according to the method described in Brode, "Chemical Spectroscopv," John Wilry and Sons Inc New I'ork N Y 1'239 jt 373
fro111 the fruit of the osage orange tree ( l l l a c l u n ~ pornifera Raf.). 'fhe name pomiferin is assigned to this substance and it is shown that the experimental data so far obtained harmonize with a provisional formula of CzaHz&hj. 2 The basicity of osajin is shown to be more in harmony with an acidic phenolic structure than with a lactone structure. .1 The substance previously described as osajic acid di-p-~olueriesulfonate~ is shown to be pomiferin di-p-tolueriesulfonate. i ( kajin forms a mnno-p-toluenesulfonatc (m. p. 152'). 5. The melting point of osajin diacetate is established as I @Lo. 6. A diacetate, triacetate, dimethyl ether, trimethyl ether, and dimethyl ether monoacetate of pomiferin have been prepared. 7 . Both osajin and pomiferin are isomerized by sulfuric acid -glacial acetic acid mixtures to high-melting, colorless, crystalline substances. h. Pomiferin di-p-toluenesulfonate is isomerized under the same conditions and the product is identical with the reaction product formed between iso-pomiferin and ptoluenesulfonyl chloride. $9. The absorption spectra of osajin, iso-osajin, pomiferin and iso-pomiferin have been observed. COLUMBUS, OHIO
RECEIVEDA u c v s ~c), 193Y
[ C O N T R I B I ' T I O N FROM THh C H E M I C A L LABORATORY OF ICJWA STATE C O L L E G E ]
Dibenaofuran. XIII. Orientation and Substituted Amines' B Y HENRYGILMAN,
PAUL
'r. PARKER, JAMES
Introduction Incidental to the determination of structure of substituted amines, it is now shown that the generalizations on orientation postulated previously? are adequate for the predominant products which result from polysubstitutiori of the dibenzofuran nucleus. lilitration.-Nitration of a monosubstituted dibenzofuran having a strongly meta-orienting group proceeded heteronuclearly and the entering p went largely to the 7-position, and the was involved only to a subordinate extent. The nitro acid obtained from nitration of 2(1) Paper XII, THISJOURNAL, 61, 1371 (1939) (2) Gilman, Brown, Bywater and Kirkpatrick, ibrd, S6, 247.1 (1934); Gilman, Van Ees and Hayes, ibid , 61, 643 (1939) Ser also, Cnllinane J Chcm 50c 2X65 (193?)
c. BAILIEAND GEORGEE. BROWN
acetyldibenzofuran was identical with that obtained from nitration of methyl 2-dibenzofurancarboxylate. The same acid resulted by oxidation of the acetyl-3-nitrodibenzofuran prepared by a Friedel- Crafts reaction with 3-nitrodibenzofuran. The chief nitro ester obtained by nitration of methyl 3-dibenzofurancarboxylatewas methyl 2 nitro-7-dibenzofurancarboxylate. The positioii of the nitro group was shown by hydrolysis to a nitro acid which on decarboxylation yielded 2riitrodibenzofuran. Nitration of 1-acetamino-4-methoxydibenzofuran took place homonuclearly, as might have been predicted, and the nitro group was directed ortho to the acetamino group. The structure of
Oct., 1939
ORIENTATIONAND SUBSTITUTED AMINESOF DIBENZOFURAN
2837
0
the l-acetamino-2-nitro-4-methoxydibenzofuran thermore, the nitrobromo compound obtained by has now been was established by reduction and cyclization to a nitration of 3-bromodiben~ofuran~ methoxy-imidazole. Incidentally, i t was shown shown to be 3-bromo-7-nitrodibenzofuran because catalytic reduction replaced the bromine by hydrogen and reduced the nitro group to give 3aminodibenzofuran. A similar reduction of the nitro-4-iododibenzofuran did not reduce the nitro group appreciably, and the chief product was 3I OCHs nitrodibenzofuran. that the nitro group did not go ortho to the methBromination and Thiocyanogenati0n.-Bromioxy group, for the replacement of the original nation of ethyl 2-dibenzofurancarboxylate gave acetamino group by hydrogen gave a nitro-4- ethyl 2-bromo-8-dibenzofurancarboxylate.This methoxydibenzofuran unlike the known 3-nitro-4- structure followed from the fact that the bromo methoxydibenzofuran. a acid obtained by hydrolysis of the bromo ester was The nitration product of 1-bromo-4-methoxydi- identical with the bromo acid obtained by oxidabenzofuran was shown to be l-bromo-3-nitro-4- tion of the Friedel-Crafts acetylation product of methoxydibenzofuran, for debromination and re- 2-bromodibenzofuran, duction gave a quantitative yield of the known Thiocyanogenation of 3-aminodibenzofuran in3-amino-4-methoxydibenzofuran. troduced the thiocyanogen group either into the Nitration of 2-acetyl-7-acetaminodibenzofuran 2- or the 4-position because the aminothiocyanomust have introduced a nitro group ortho to the gen compound could be rearranged to a thiazole. acetamino group because reduction and cycliza- The thiocyanogeh group undoubtedly entered the tion gave an acetyl-imidazole. The nitro group 2-position. Thiocyanogenation is like halogenaundoubtedly entered the 8-position rather than tion, and i t is known t h a t bromination of 3-acetthe 6-position, for there is no case of direct nuclear aminodibenzofuran gives 2-bromo-3-acetaminodisubstitution (other than metalation) into the 4- benzofuran.6 In addition, we already have menor the 6-positi0n.~ tioned the improbability of direct substitution into Nitration of 4-bromo- and 4-iododibenzofuran a 4-or 6-position. would be expected to go heteronuclearly to a preFriedel-Crafts Reactions.-Diacetylation of dominant extent, for nitration of 2-bromodibenzo- dibenzofuran6 and acetylation of 2-acetyldibenzofuran gave 2-brom0-7-nitrodibenzofuran.~Fur- furan gave 2,8-diacetyldibenzofuran1identified by (3) Gilman, Jacoby and Swislowskp, Tma JOURNAL, 61,964 (1989). oxidation to the corresponding dibasic acid. (4) I n the preparation of pyridodibenzofurans by the Skraup Acetylation of methyl 4-dibenzofurancarboxylate synthesis with 3-aminodibenzofuran, one of the isomers involves a ring closure in the 4-position. See Mosettig and Robinson, ibid., gave methyl 2-acetyl-6-dibenzofurancarboxylate, 117, 902 (1935), and Kirkpatrick and Parker, ibid., 67, 1123 (1935). the structure of which was established by hydrolyI t is understood that a suitable accumulation of groups might force a direct nuclear substitution to the 4- or &position. sis and then decarboxylation to yield 2-acetyldi(5) Gilman, Brown, Bywater and Kirkpatrick. ibid., 116, 2473 (1934).
(6) Borsche and Schacke, Ber., 116, 2498 (1923).
28.78
HENRY GILMAX, PAPL
'r. PARKFR,
JAMES
benzofuran, and by making the reasonable :issumption that hetrroiiuclear substitution occzirs when a strongly mrta-oneiiting group IS preseii t This assumption has great validity bccaust- bro mine, which ha5 a IC~SSrnarbed lieteronuclrar or icutation effect than a cnrhomethoxy group, (11rects acylation hetcronuclearly. For example, acetylation of 2-bromodibenzofurari gave %acetylh-bromodibenzofuran, the structure of which was established by oxidation to a 2-bromodibenzofuraiicarboxylic acid, which 011 debromination yielded 2-dibenzofurancarboxylic acid. Acetylation of 2,s-dibromodibenzofuran gave 2,8-dibromo-3-acetyldibenzofuran.The structure of this product was proved by debromination and then oxidation of the resulting 3-acetyldibenzofuran to the known 8-dibenzofurancarboxylic acid. Other Friedel-Crafts reactions have been mentioned in the discussion of nitration, and the Experimental Part describes additional reactions of this kind leading to amino derivatives of the brazaii and other type, A miscellany of reactions other than those coiicerned with direct nuclear substitution are also contained in the Experimental Part.
c. BAILIF AND GEORGEE. BROU'N
5'01. 61
fliised for one hour. After standing overnight, tilost of ihc ether was distilled off and replaced by dry henzenc, and refluxing was roniinucd for one hour. The resulting
riiisturc was hytll-olyzcd by ice and 30yosulfuric acid, and I hc benzene layer was waslied with sodium carbonate solu1 ion, dried and tlis~illctlunder rcduwd pressure. The iliatcrial. I l..; p 15!)c@,distilld betwern 195-201i' ( 2 tnm. lizatioii f r o n ~~itroleuni ctF1r.r (11, p., !lO ii8 tals iiieltiiig at 9tj-96.5'. Arid. Calcd. for CI~HI!OB:C, 74.35; H, 5.83. Fountl: C , 74.42; FI, l.i.CL3,
l-~-Diethylaminoethyl-4-methoxydibenzofuanHydro-
chloride.--- Dry hydrogen bromide was bubbled through 8.8g , iO.028 niole) of niolten 1-8-hydroxyethy1-4-metho~~dibeniofuran for two and one-half hours at 100". After washing with water and recrystallizing twice from ethanol, the product weighed 2.0 g. and melted a t 91-91.5". The 1-B-bronioetliyl-4-niethosydibenzofuran was mixed with 2.0 g. (0.016 mole) of diethylamine and 2 cc. of ethanol and hpated for six hours a t 100". When cool the reaction product uas treated with 5% sodium hydroxide solution and estracted with ether. The ether solution was evaporated and the residue warmed to drive off the excess diethylamine. Saturating a n ether solution of the residual oil uith dry hydrogen chloride precipitated the salt which was purified by recrystallizing froin a n acetone-ether mixture. The yield was i.5 g . \,C8yoo)of hydrochloride melting a t 1%' with decoiiipositiori. A n d Calcd. for C,gH&NCI: N, 4.20. Found: N, 4.26 and 4.43. 1-Acetyl-4-methoxydibenzofuran-A Friedel-Crafts reExperimental Part wtion was effected with 10 g. (0.05 mole) o€ 4-methoxydiNuclear Substitutions of 4-Derivatives henzofuran in 50 cc. of carbon disulfide, 6.8 g. (0.05 mole) 1-Bromo-4-methoxydibenzofuran.-A solution of 27 5 of alutninum chloride and 4.0 g. (0.05 niole) of acetyl chlor,v (0 17 mole) of bromine in 170 cc of acetic acid was added idt, One recrystallization of the crude material from in several portions t o a solution of 34 g (0 17 mole) of 4- ethanol gave 8.0 g. (66%) of product melting at 132-138". methoxydibenzofuran in 340 cc of acetic acid at rooiii A% second recrystallization raised the melting point to 13.4I eniperature with shaliing Dciolorization was iminedidti i:ii 5 ,. After standing overnight the pioduci was thrown t i u t ot :ln[iZ. Calcd. for C16H1103:C, 74.97; H, 5.04. Found: Lolution by diluting with water Crystallization from C, 74.li6and 7.5 3iJ: H, 5.42 and Fj.39. ethanol gave 42 g. (887') of material melting at 96-'T" Oxidation of 1 g. (0.004 mole) of the l-acety-4A xcond recrystallizatioii gave the pure product nieiting rnethoxydibenzofuran in 130 cc. of water containing 2 g. at 97-97 5 " which showed no depression in inelting point of sodium hydroxide with 3 g. (0.019 mole) of potassium when mixed with a n authentic specimen prepared by the permanganate gave a 90% yield of 4-methoxy-1-dibenzomethylation of 1-bromo-4-hydroxydibenzofuran furancarboxylic acid (mixed m. p.), 4-Methoxjr-1-dibenzofurancarboxylic Acid. - -The GrigThe oxime of 1-acetyl-4-methoxydibenzofuran was obnard reagent prepared fiom 5 g. (0 018 mole) of 1- b r o m o 4 tained in a11 88% yield, and melted at 176-177.5" after methoxydibenzofuran and 0 5 g. ( 0 02 g atom) of magne- crystallization froin ethanol. iium in a mixture of 25 cc of ether and 10 cc of benzene A n d . Calcd. For Cl,jHI,j03N: K, 5.49. Found: N, was carbonatcd in the custoniarv manner A yield of 2 7 5.44. g (S2c/o) of the pure conipoiind (crystallization from ethaBeckmann Rearrangement of the Oxime from 1-Acetylnol) was obtained melting at 219-280" with deromposi4-methoxydibenzofuran.-The rearrangement was effected tion in 95% yield by treating a suspension of the oxime in ben11vru1. Calcd for Ci4H,~04C, 69 10, El, 4 13 Found zene with phosphorus pentachloride. The resulting 1C , 69 67 and G9 00, H, 3 61 and 4 BO acetamino-4-methoxydibenzofuran melted a t 222--223 I-p-Hydroxyethyl-4-methoxydibenzofuran.-To a n ice- after crystallization from ethanol. cold solution of the Grignard reagent prepared From 22 2 A n d . Calcd. for Ci6Hl3O3N: N, 5.19. Found: N , g (0 08 mole) of 1-hiomo-4-methoxydibenzofuran was 5.43 and 5.37. added 8 0 g (0 18 mole) of ethylene oside The solution Refluxing a solution of 2 g. (0.008 mole) of the l-acetwas allowed to warm t o room temperature and then reamino-3-incthosydibcnzofuranin 200 cc. of 95Yo ethanol - will! tXl PC. of conrd. hSdroc*hloi-icacid gave a 917, yield :I
