N-Acetyl-2,5-diiodohistamine. -The reavl ioii of 0.6 g of N-aretylhistamine with 1.52 g of 1 2 was performed as described for the other compounds. After addition of KIOI and extraction of I,, alkalinization to pH 8 produced a white voluminous prrcbipitate. The compound was obtained i i i a final yield of 0.45 g (84cc), melted at 214-216", arid gave one spot o r i tlr w i t h Rt 0.80. .InaZ. (C,ETqT?SaO.H20)C, H, I, S .
Acknowledgments.-We \I ihh t o thank Professor5 1'. C. 1;crreira arid 31. llotidome for valuable advice : ~ n d help in thc preparation of ?;-:icet?-lhistamiiir., I'rofes5or T. B. I'aiva for the biological I l l r . A. Hashimoto for the determination of nmr ipec tra. Sy-nthesesof Benzoniorphan and Related Compounds. 11.' The Debenzylation of Quaternary Ammonium Salts with Thiopheno12
aniinoi1iuni salts w ~ r econfirniccl by iiiicioan:il Quite natiircilly, benzyl phenyl ttiioethcr') arid 01' . phenyl thioether16mere detected 3s by-product 1i i ihiz ww, S a O H is thought to react n-ith an cquiiiiolar ;mount ot tliiopheiiol (cj. reaction 9 in 'I':ible 11) i i i the first place, and the resulting thiophmo\idc :tiiir)ri i. ail efiectivc riucleophile but r i o t k caiihe Hofmann degradatioii. an application of this method, :I rnoclificd syiiof pentazocine (I), I s Iianiely, 1, 2 , ~ ~ ; ~ . ~ , ~ j - l i e x : ~ - X - hydroxy- 2,6- methmo-B,11 -dimethyl - 3 - (3,:4di~i~ethyl:tll~l)-~~-berizazocine, :I very effect ivc ;ui:i1getic agerii \Tit11 no dependencr liability. hay bwn invp.1 igatcd. 111 the previouh paper,' WP Iiu~cz.tlre:~tl~. I cyorted thc syntheses of sever:il quaternnry :irnmoniuni \:ilt\ (I1 IV) which were important intermedi:itca 101. ~)c~it:tzocine.lye also have reported t h a t iliv I diicstivc dcheiizylation of IV hy cdtulytic liytlrogcii :I. I I o n nff orded t hr expected pentazocine. but simult:incou* i d u c t i o n of thc double bond occ~urrcd. S o t prihingly. t r e a t r w n t of tn o tiuat e r n x y :iniiiiooiiiiii salts (I1 aiid 111) with thiophenol in aqucous S:iOH Olliy \..I: rlr tilcA of 117~t iHordecl :i mixturcx ut I (51.0 iormcd i i i ,X.i' 6 ( ig of 17.' with o\w- - o c l j i i n i t I i j o p l i c ~ i i oxidc in a n orgtliiic solvent. lis
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li. KIGis i n 1, AI. Him \ & I , N. WAGLISLMI, K. 11-\[CIS II< i, \VI1 0. Kus 1x1 \
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f'liarmaccut Lcal Instztule, Tohokz~Cnzwrszfy, Aobayama, Sendai, Japun, and Research Laboralor ies, G e l a n Pharrnaceutical Company Ltcl , Sakurushinmachi, Setagayaliri, Tokyo, Japun
12cceizecl Febi itar y 3, 1969
Shamma and his comorliei*s3had successfully eniployed sodium thiophenoxide in the demethylation of a variet,y of quaternary salts and proposed that the reaction proceeded by Ss2-type displacement. I n view of the fact that the benzyl or allyl are much better leaving groups than methyl in riucleophillic displacement, we have investigated the selective K-debenzylation or S-deallylation of a number of quaternary animonium salts with t'hiophenol in the presence of 5-20?;> aqueous KaOH. From various K-benzylammonium salts with other S-alkyl groups, the corresponding debenzylated tertiary amines were obtained selectively as shown in Table I. The cleavage of C--X single bond by pyrolysis4 or by treatment with inorganic salts containing S5 has been ltriorvri in the case of both allylic and benzylic s&s. Therefore, an investigation was made whether either selective debenzylation or deallylation would occur in the several K-allyl-N-benzylammoniuin salts and a greater ratio of deallylatiori to debenzylatiori was observed in all cases in Table 11. A11 the tertiary amines obtained in Tables I and I1 wort found to be identical with authentic samples as free bases and/or their salts by mixture melting point, ir spectral, arid tlc compari~ons.4-~4The unknown ( 1 ) P a r t I : T. Iiainetani, li. l\igasa\ra. 11. Iiiiragi, T. Hayasaka, N. \\agatsiirna, and K. K a k i . Heterocyclic Chrm.. 6 , 43 (1969). 12) This forms p a r t CC S V of studies on t h e Syntheses of Heteror , y c l i o Compounds. One part of this work is reported: T. Rametani, li. Kigasawa. .\I. Hiirari, h-. Wagatsuma. a n d K. Wakisaka, Tetrahedron Letter,-, 635 (186Y). ( 3 ) 11. Shamma, N. C. Ueno. and J. h'. Kemar, i b i d . , 1375 (1966). (4) U. R. Tarbelland J . R. Vaiighan, Jr., J . A m . Chem. Soc., 65, 231 (1943). ( 5 ) €1. It, Snyder and J. C. Speck, ibid., 61, 668, 2895 (1939). 16)T. 'I'iiornson and T. S.Stevens, .I. Chem. Soc., 1932 (1932). 17) .I. .L. Harltrop and D. A. H. Taylor, i b i d . , 108 (1951). ( 8 ) .I. I.. D u n n and T. S.Stevens, tbtd., 1Y26 (1932). ( 9 ) A I'artheil and H. von Broich, Ber., 30, 618 (1897). 1 1 0 ! T. .J. King, J . Chem. Soc.. 8YS (1951). (11) .J. V. Rraun, Ber., 37, 2920 (1904); 1;. Ilasse and I nant1 ,I.
Ilird. .I. .\fed, Chvni., 7, 123 [19R4!. (19) All melting points and boiling point8 were not corrected.
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KOTES
July 1969
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allized to give the correspoiidiiig salts as ( 5 ) Reaction of I\ with Sodium Thiophenoxide in Organic shown in Table 11. Solvents.--ii mixture of 2 g of I V , I 15 g of C6H ( 3 ) Reaction of N-Benzyl Tertiary Amines with 3,3-Diml of Zbutanone wa, heated o i l i i \\:itel bath at I methylallyl Bromide.--A mixture of 1 molar equiv of tertiary 4fter additiciii of .TO ml of 1120 to the ieacilou I I I I amine and 3,3-dimethylally.l bromide in dry Me&O was refluxed e\tiactioii m t h CIIClp, the ('HC!ld lale 011 a water bath for 1-5 hr in the presence of dry NaHCOa.20 After give a reddue, which waz extracted m t t h 10 completion of the reaction, the solvent was distilled, and the tan1 acidic w h i t i o n a a 5 basified n i t h % t i residue was extracted with E t O H in order to remove an inorganic. extracted nith CIICIa The extlact w a y reagent and filt'ered. Evaporation of the filtrate gave the corrervaporated tu give a broan c.arsme1, i\hich xvai piuified I)\ sponding salts as shown in Table 11. -ilicic acid c*hroinatugraphy ~iaiiigEt,O, Et ( 4 ) 1,2,3,4,5,6-Hexahydro-8-hydroxy-2,6-methano-3,6,11- and 3leOII a . eluent Removal (Jf E t - 0 gave 0.iI trimethyl-3-(3,3-dimethylallyl)-3-benzazociniumIodide (111): ~1'1, F here%
