Sept. 20, 19d4
NOTES
4617
Use of the Stenhouse Reaction for the Preparation obtained directly from concentrated solution in of Mixed Dianils of 2-Hydroxyglutaconaldehyde methanol or ethanol melted a t 157", while that obtained by recrystallization from methanol melted B Y CARL\'. BROUILLETTE. IVILLIAM M. FOLEY, JR.,'" AND a t 174". Both compounds gave the correct eleHERBERT MCKENNIS, JR.'~ mentary analysis for the expected unsymmetrical RECEIVED JANUARY 9, 1954 dianil. Moreover, their absorption spectra were Previous studies have shown that the Stenhouse quite similar. The explanation may lie in simple reaction2 may be employed to form a wide varietyza polymorphism. An examination of structure I , of symmetrical dianils of 2-hydroxyglutaconalde- however, reveals many opportunities for geometrihyde. -4 recent report from this Laboratory3 dis- cal isomerization (syn-anti, cis-trans) as well as the cusses various proposals which have sought to possible existence of tautomeric forms. Tentatively, explain the mechanism of the reaction and reviews therefore, the higher melting product is called form A and the lower melting form B. much of the earlier literature. One characteristic of many dianils of 2-hydroxy€I \ + / H P" glutaconaldehyde is their instability. I n acidic solution l-phenylimino-5-phenylamino-2-hydroxypenta-2,4-diene, a symmetrical dianil of 2-hydroxyglutaconaldehyde, undergoes ring closure with the N-phenyl-3-hydroxypyridinium formation of salts2s4*5 and the elimination of aniline. The mechFor the preparation of 1-phenylimino-5-p-bromoanism of this reaction is not entirely clear. The aryl- phenylamino-2-hydroxypenta-2,4-diene hydrochloamine in either the 1- or &position of the dialdehyde ride, stoichiometric amounts of N-p-bromophencould be cleaved during the formation of the pyri- ylfurfurylideneimine and aniline hydrochloride dol. I t occurred to us, therefore, that the reaction were allowed to react in ethanol. The expected d i a d of various anils of furfural with aromatic amines could not be isolated readily from the reaction mixother than those parent to the original ani1 might ture. The product invariably gave carbon, hydroprovide a source of useful unsymmetrical dianils. gen and bromine analyses, despite repeated recrysRing closure of the latter should yield various K- tallization, which suggested contamination by the aryl-3-pyridols and provide an insight into the 1- 9 - bromophenylimino - 5 - p - bromophenylamino mechanism of ring closure. The unsymmetrical di- compound. When the reaction was carried out in anils previously have not received systematic study the presence of three equivalents of the bromoanil although aniline and various other aromatic amines and one mole of aniline hydrochloride, the isolated together with furfural and acid have been used to product was indeed l-N-p-bromophenyliniino-5-Nform resinous materiak6s7 Schiff8 studied reac- 9 -bromophenylamino - 2 - hydroxypenta - 2,4 - diene tions of furfural and mixtures of aromatic amines hydrochloride. Conversely, when three equivain the presence of acid but did not report details. lents of aniline hydrochloride were employed with The preparation of l-arylimino-5-arylamino-2-one mole of the bromoanil, the product obtained hydroxy-penta-2,4-diene salts where both aryl was, by analyses, virtually free of the bis-bromo degroups are the same in general offers no great dif- rivative. These experiments serve to suggest the ficulties other than those associated with the pre- possibility of a redistribution reaction. viously noted hygroscopic nature and instability In the analogous preparation of l-p-hydroxyof the product^.^ Boehmg has reported the affin- phenylimino - 5 - phenylamino - 2 - hydroxypenta - 2,4ity of these substances for many solvents of crys- diene hydrochloride from N-p-hydroxyphenylfurtallization. I n attempting to prepare 1-N-p- furylideneimine and aniline hydrochloride no such phenylazophenylimino- 6 - phenylamino - 2 -hydroxy- difficulties were encountered, and the expected penta-2,4-diene hydrochloride from N-p-phenylazo- product was obtained readily. Rombaut and phenylfurfurylideneimine and aniline hydrochloride Smetsl reported that 9-aminophenol and p-anisisome difficulties were encountered. After investi- dine are displaced from furfural by p-aminodiethylgating various means, it was found that the product aniline and that p-nitroaniline is displaced by p(1) (a) Stauffer Chemical Co., Torrance, California. (h) Medical anisidine. College of Virginia, Richmond, Va. Furfurylideneimines, employed by us, were de( 2 ) J . Stenhouse, A n n . , 156, 197 (1870), first described molecular rived from p-aminoazobenzene, p-hydroxyaniline reactions involved in t h e cleavage of t h e f u r a n nucleus oi 2-furaldehyde and p-bromobenzene. All these imines show absorpin t h e presence of acid a n d aromatic amines. ( ? a ) T . H. Zincke and tion maxima in the range 325-370 mp. The maxiG . l l u l h a u s e n , Be?., 38, 3821 (1905). (31 W. M . Foley, Jr., G u y E. Sanford and H. RlcKennis. Tr., THIS mum for the unsubstituted phenyl compound, NJ O I J R N A I . , 74, 3189 (1952). phenylfurfurylideneimine, lies a t 320 mp. The ob(4) J . C. XTcGowan, J. Chein. .Yoc., 777 (1949). served shifts of the maxima to longer wave lengths ( 5 ) C. F . Koelsch and J. J. Carney, THISJ O E R N A L , 72, 2285 (1950). are in agreement with the generally observed shifts ( 0 ) (a) XI. Phillips and G . Llain?, Chem. and M e t . E n g . , 24, 6G1 (1921); (b) H. F . Winterkorn, U. S. P a t e n t 2,314,181, M a r c h 16, 1943. attributable to increased conjugation and intro(7) J. R o m b a u t a n d G. Smets, Bzdl. SOC. chim. Beig., 58, 421 (19491, duction of nuclear substituents on the benzene have investigated t h e reaction of furfural with aromatic amines in t h e ring which enhance the resonance possibilities. lo absence of added acid. Bases were obtained with empirical formulas corresponding t o free bases which might be expected f r o m various unsymmetrical Stenhouse dyes. T h e reported stability of t h e former in acid, however, suggests t h a t t h e compounds are isomeric with free bases of t h e t y p e prepared b y McGowan.4 (8) H. Schiff, A n n . , 2S9, 349 (1887). (9) T. Boehm, Arch. P h a r m . , 267, 129 (1929).
Experimental N-p-Bromophenylfurfurylideneimine .-p-Bromoaniline (17.0 g.) and 9.59 g. of furfural were placed in a small (10) G N. Lewis a n d M . Calvin, Chcm. Revs.,26, 273 (1939).
NOTES
4618
VOl. 76
2.09 g. of p-bromoaniline hydrochloride in 25 ml. of :hsolutc alcohol was added with stirring. On standing, the solution deposited 1.4 g. of purple dianil hydrochloride, m . p 159-160' dec. The crystals were collected and washed with alcohol-ether (1-1). For analysis the compound was drier1 under diminished pressure. Recrystallization from :rhsolute alcohol did not affect the melting point of the crystals. An additional amount of product was obtained from the mother liquors to give a total yield of 3.92 g. (86%). C,~ I44.5; : H, 3.3. l-N-p-phenylazophenylimino-5-phenylamino-2-hydroxy- Anal. Calcd. for C I ~ H I S S Z O C ~ B penta-2,4 - diene Hydrochloride.ll-S - p - Phenylazophenyl- Found: C, 44.6; H, 3.3. furfurylideneimine (2.75 g.l*; Amax, 225, 240, 367 mp; log e Acknowledgment.-The authors wish to thank 4.16, 4.15, 4.24; Amin. 233, 267 mp; log e 4.15, 3.85) was T. Redemann, Mr. Robert J. Brotherton Dr. Carl dissolved in a minimum amount of anhydrous ethanol, and L. Alumbaugh for the microand Mr. Robert 1.29 g. of aniline hydrochloride was added. The solution turned purple and deposited 3.29 g. (81%) of purple crys- analyses, and Mr. Elmer Streed, all of this Laborntals, m.p. 157' dec. The product was washed with an ex- tory, for the determination of the nlxwrpticm cess of ether-alcohol (2-1) and then dried under diminished spectra. pressure. The melting point and color were unaltered. BASICSCIENCES RESEARCH DEPARTMENT Fresh solutionsS of the dianils were examined in absolute 245, 310, 395, 555, 590 mrr; log c U. S. NAVALCIVILENGINEERING alcohol: form A, Lax. RESEARCIT AND EVALUATION LABORATORY 4.24, 3.96, 4.65, 3.60, 3.58; Amin. 230, 290, 515, 580 nip; PORTHUENEME, CALIFORNIA log e 4.22, 3.92, 3.51, 3.45. Anal. Calcd. for CIJHPIN,OCl: C, 68.2; H, 5.2; N, 13.84; C1, 8.75. Found (cor. for ash): C, 67.6; H, 5.1; N, 13.85; C1, 8.6. Isomerization of Isospirostans to Furostenols with Conversion of Form A to Form B.-The lower-melting mridine Hydrochloride as the Catalyst form was dissolved in methanol at room temperature. The solution was chilled, and the purple crystals were washed BY \vILLIAM G. DAUBEN A N D GERIIARD J. r O N K F \ with methanol-ether; m.p. 174' dec. Further recrystalliRECEIVED MARCH 25, 1954 zation and drying under diminished pressure did not alter 245, 295, 392, 540 mp; log e 4.24, the melting point; A,, The isomerization of an isospirostan to a furo3.93, 4.54, 3.73; Amin. 230, 290, 320, 500, 610 nip; log e stenol was studied by Gould, Staeudle and Hersh4.19, 3.92, 3.91, 3.63, 3.61. Anal. Found (cor. for ash): C, 67.8; H , 4.9; N, 13.8; berg' and they found that the conversion coul(l be C1. 8.7. achieved a t the boiling point of acetic anhydride in Claisen flask in a bath a t 130". The fraction, b.p. 89" (3.5 mm.), was collected (23.1 g., 92'%). For analysis the product was recrystallized from n-hexane to yield pale yellow crystals, m.p. 62.5-63". Absorption spectra were obtained on this and related azomethines a t concentrations of approxi225, 287, 325 mp; mately M i n absolute alcohol. A,,. log e 4.11,4.27,4.30; Amin. 250,303 mp; log e 3.59, 4.26. Anal. Calcd. for C1IHsSOBr: C, 52.82; H, 3.22; N, 5.60. Found: C, 52.97; H , 3.22; N, 5.68.
l-N-p-Bromophenylimimo-5-phenylamino-2-hydroxypen-the presence of a Lewis acid such as aluminum
ta-2,4-diene Hydrochloride.-S-p-Bromophenylfurfurylichloride or acetyl chloride. Similar conditions, deneimine (0.83 9.) was dissolved in a minimum amount of anhydrous ethanol. A solution of aniline hydrochloride using acetyl chloride, also have been employed to (1.3 g.) in anhydrous ethanol was added, and the mixture convert A4,6-22-isospirostadiene-.'3.-oneto the corresponding 3-acetoxy-3,5,'T-triene.? Allthough this was allowed to stand. The purple crystals (0.5 g., 40%). m.p. 151" dec., were collected and washed with anhydrous latter reaction was complicated by the tendency o f ethanol. The melting point and color were unchanged upon repeated~ecrystallizationand drying under diminished the starting ketone to f orm 3 ,%-diacetoxy-3,5,T,The compound was extremely hygroscopic 20(22)-furostatetraene, the rnaior product always pressure a t 76 and retains one molecule of water of crystallization upon contained the side-chain intact. In contrast, exposure t o moist air. however, when the enol acetylation was conductctl Anal. Calcd. for C ~ I H I ~ N ~ C ~ O B ~C, . H ~51.3; O : H, in the presence of one equivalent of pyridine (per 4.56; N, 7.05; Br, 20.10; CI, 8.92; HzO, 4.Fj3. Foiind: C, 51.6; H, 4.4; pu', 6.99; Br, 20.01; CI, 8 88; H20 (by mole of steroid), the enol acetate of furostatetraenc was obtained in a yield of 40yo. In view of t h c s loss of weight a t 100" under diminished pressure), 4.51. 1-N-p-Hydroxyphenylimino-5-phenylamino-2-hydroxy-increased reactivity of the reaction system toward penta-2,4-diene Hydrochloride.-To 7.0 g. of N-p-hydroxyisospirostan ring isomerization when the pyritliiic phenylf~rfurylideneimine'~ in 50 ml. of ethanol, a solution was present, the role of this base in sucli :I ccmvc-rof 4.9 g. of aniline hydrochloride in 20 ml. of ethanol was added. On standing, the solution deposited 8.3 g. (70%) sion has hecii ev,ilitntc~d. of purple crystals, m.p. 163-166" dec. For analysis the compound was recrystallized from ethanol and dried under diminished pressure. The purple product melted at 171250, 292, 520 m p ; log e 3.93, 3.83, 4.18; 172" dec.;. , , A, Amln. 230,272,400 mp; log e 3.87,3.78,3.61. Anal. Calcd. for C17H17X20~Cl: C, 64.46; H, Tj.41; N, 8.85. Found: C, 64.76; H, 5.71; N, 8.81.
.
1-p-Bromophenylimino-5-p-bromophenylamino-2-hydroxypenta-2,4-diene Hydrochloride.-To a solution of I .72 g. of p-bromoaniline in 20 ml. of absolute alcohol was :ddetl 0.96 g. of furfural. The mixture was heated to 60 and then allowed to cool to room temperature. A solution of (11) For simplicity of nomenclature i t is aisiimed throughout this p a p e r t h a t n o interchange h a s c a u s ? r l in\-ersiun o f s u h s t i t ~ i r n t sI??. tween t h e 1- and 5-positions. f l ? ) hl. Betti, GQZZ.chiin. i t a l , , 281, 248 (1808,. (18) I € . Schiff, AN^., 201, %7,5 (18801, prepared this cumpound. III.IJ. 180--18L'0. Our imine rrlitnineil h y recry?tallizuti
