Communications-Reactivity of 2,6-Di-t-butylpyridine Toward

Mar 5, 2003 - Communications-Reactivity of 2,6-Di-t-butylpyridine Toward Sulfur Trioxide at Elevated Temperature. H Van Der Plas · T Crawford · Cite T...
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B y the same general method, 16-hydroxymethylene-3-ethylenedioxy-5-androsten-17-one [m.p. 203206'; (a)D +26.8'], prepared from X-ethylenedioxy-3-androsten-l7-0iie,~6 gave the corresponding 16 (-cyano derivative [m.p. 240-242'; ( a ) , f4.3' (*21', c 0.2311 which was converted to 16t-cyanotestosterone [m.p. 218-219'; ( a ) , +88.5'; A,, 240 mp ( e 16,170)] by lithium borohydride reduction and acid-catalyzed removal of the ring-A blocking group. 16 - Hgdroxymethyleiieestroiie 3 - methyl ether17 and I yielded 16t-cyanosterone 3-methyl ether [m.p 138-148'; ( a ) , +189'] which on subsequent reduction with lithium borohydride afforded 16&cyanoestradiol 3-methyl ether [m p. 197-200'; (a)D +54']. The results of the as yet incomplete biological evaluation of these compounds will be reported in a forthcoming paper. S o outstanding endocrinological activities have been discovered thus far. ORGANIC CHEWCAL RESEARCH SECTION LEDERLELABORATORIES DIVISION A4MERICAS CYAUAVID C O . PEARL RIVER,X. Y.

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Instead, together with unchanged 2,6-di-t-butjrlpyridine (30-35%) and the 3. sulfonic acid (3035%), a compound was isolated (15-20%) melting a t 140-141 '. It was insoluble in water but easili soluble in ether and ethanol. From elemental analysis and molecular weight determination its composition was established as C13H19N02S. Anal. Calcd. for ClsH19S02S:C, 61.62; H, 7.56; X, 5 . 5 3 ; S, 12.66; mol. wt. 253. Found: C, 61.9; H, 7.4; E, 5.5; S, 12.1; mol. wt. (according to Rast) 245. Taking into account its composition, mode of formation and the fact that the compound could not be hydrolyzed in an alkaline medium, it was considered to be best represented by structure I,4 2,3dihydro-3,3-dimethyl-5- t-butylthieno [3,2- blpyridine l-dioxide.


Received March 13, 1961 (16) H. J. Dauben, Jr., B. Lolren, and H. J. Ringold, J . Am. Chem. Soc., 76, 1359 (1954). ( l i ) J . C. Bardhan, J . Chem. SOC.,1848 (1936).

Reactivity of 2,6-Di-t-butyPpyridine Toward Sulfur Trioxide at Elevated Temperature

Sir: It has been known for several years that 2,B-di-tbutylpyridine can be sulfonated with sulfur trioxide a t low temperature. l I n an extensive investigation of the reactivity of 2,G-dialkylpyridines one of us (v. d. PLj, together with den Hertog, has shown that during this reaction the sulfonic acid group entered the 3-p0sition,~-~ as in the sulfonation of pyridine below 300'. Since sulfonation of pyridine above 300' leads to the formation of pyridine-4sulfonic acid and 4-hydroxypyridine1 together with the 3-sulfonic acid,5we also studied the behaviour of 2,6-di-t-butylpyridine toward sulfur trioxide at elevated temperatures. When 2,6-di-t-butylpyridine was heated with sulfur trioxide a t 240-250' for fifteen hours in a sealed tube, neither 2,6-di-t-butylpyridine-4-sulfonic acid nor 2,6-di-t-butylpyridone-4 was formed. (1) H. C. Brown and B. Kanner, J. Am. Chem. Soc., 75, 3865 (1953). (2) H.C.van der Plas and H. J. den Hertog, Chem. Weekblad. 53, 560 (1957). (3) H. C . van der Plas and H. J. den Hertog, Tetrahedron Lrliws, KO. 1, 13 (1960). ( 4 ) H. C . van der Plas, Thesis, Amsterdam, 1960. ( 5 ) H. J . den Hertog, H. C. van der Plas, and D. J. Buurman, Rcc. Trav. Chim., 77, 963 (1958).

We now wish to report that this conclusion was correct. The infrared spectrum of I in chloroform shows two strong bands a t 1134 cm.-l and 1316 cm.-l, both indicating the presence of a sulfone group in the molecule.6 That no rearrangement of the t-butyl group occurred during heating of the 2,6-di-t-butylpyridine with sulfur trioxide was established by considering the XhIR spectrum of I (internal reference tetramethylsilane, solvent tetrachloromethaiie, 60 mc., magnetic field approximately 14,100 gauss). In this spectrum two peaks were observed with ~-values,'2.38 and 2.88, both peaks being characterized by doublet structures with coupling constants J = 8 c.p.s. The 7-values agree with those given for the p- and y-protons of the pyridine nucleus.8 The coupling constants, J = 8 c.p.s. also affirm the presence of both p- and yprotons in the pyridine nucleus, being in good agreement with JOY = 7.35 c.p.s. given for 2,3-substituted pyridine^.^ These data exclude the possibility of an a-proton being present in the pyridine nucleus. Further, the KMR spectrum shows peaks at 7-values 6.74, 8.43, and 8.63, attributed, respectively, to the proton resonance peaks of the methylene-, the two methyl groups, and the t-but 1 group. The intensity ratio of these three peaks, 2 :6.1 :9, supports these assignments. The paramagnetic shift of the protons of the methylene group is due t o the deshielding by the adjacent electron-withdrawing sulfone group. (6) L. J. Bellamy, The Infrared Spectra of Complex X o i e cules, John Wiley and Sons, Inc., New York, N. Y., 1958, page 360. ( 7 ) G. V. D. Tiers, J . Phys. Chem., 62, 1151 (1958). (8) L. H. Jackman. Applzcation of IYuclear Mugnetzc Resonance Spectroscopy in Organzc Chemtslr y, rcrgamon Press, New York 1959, page 64. (9) H. J. Bernstein, J. ,4.Pcple, aiid IT. G. Srhneider, Can. J . Chem., 35, 65 (1957).





The infrared and the IYMR data thus provide strong evidence for structure I. The peculiar formation of a siibctitiited dihydro-t hiopheiie ring from a rcactioii of sulfur trioxide 011 an alkylated aromatic compound has not previouslg been reported and an invedigation of the mechanism of this reaction and Its applicability to other compounds is being continud.

of benzoic acid, while mesitoic acid gives hydroxide ion to the solvent to form four particles for crcry molecule of n:cqitoic acid. l'resumably, the elcclron concentration a t the carboxylate end of mcsitoic acid could Ise due to the electron donat:osi 1 y ortho-para methyls, transmitted by r(wti:,ii C > through the benzene ring. Thus, it scerrs pcs ih e that electrons could be withdrawn from tEc ate ion a t the anode to give the Kolke reaction. A clznowledgment The authors are indebted t o Attempted Kolbe electrolysis of pot%, CTlUrn _' mesiProfessor Dr. H. J. den Hertog (Wageiiingen) for toate iii water showed that during the coiirse of many helpful discussions and to Professor Dr. reaction measurable amounts of carbon dio~.idezpRichard FI. JT'iley (Louisville) for use of the S M R peared in the anode gas. The electrolytc turned spectrometer. dark with no oil or solid separating, except a minutc I , Z R O R 4 r O R Y OB H C. VAN DER PLAS'~ amount of yellow ether-insoluble materikll judged ORG4KlC ClIEVI7TDY polymeric. Xhsence of other insolublc nia tcrin 1 akQRICULTTTRAI,~ T h I V E R S I T Y negates the formation of any hydrocarbonq R R , WLGENIUGC~ (R minus H), or rresityl mesltoate, RCOOII THFJ S E T I I E R T A K D S AAS DCPART\.IHUl' O F CHEMISTRI T 1%.C R A T E O R D ~ ~ ROB is a frequent Kolbe product, mwitol n ~ s sought In the dark electrolyte Coni entional org~iiic 1-NIVERSITY 01 LOLIWILLE qualitative chemical analysis yielded negati\ e T,OUISVILI.E 8, K Y results. Received March 22, 1961 According t o Porter and Thurberj6 mesitol is ( 10) Temporary addrws: University of Louisville, oxidized by silver oxide to give a quinone free TJouisville 8, Icy. ( I 1) National Sricnce Foundation Cooperative Graduate radical of the mesitol, which bp proton 1)ondingwith a molecule of mesitol gives a i l analogue of quinh Fcllow. drone. It is conceivable that the electroly-'+lS 0 , mesitoic acid should yield such a quinhydronctype organic coxpound by anodic oxidation I f Aqueous Mesitoate Electrolysis, ArOH is present. Kolbe-Inhibitedl Isolation of this compound was attemptcd without success. Polarographic analysis shows no siviAir: larity betn-eeii the chemically oxidized and the We wish to report that the aqueous potassium electrolyzed compounds. 2,4,6-trimethylbenzoate fails to give typical Kolbe We therefore conclude that ring-rupture by anodic products on c l e c t r ~ l y s i sThis . ~ failure will be termed oxidation accounts for the carbon diovide and polymer, and that mesitoic acid is aromatic-iiihihitetl Kolbe inhibition. Rolbe inhibition is more common in water than in water. We hypothesize that either carbovylatc in organic solvents and the feature of inhibition electron congeqtioii does not occur upon this acid in water i. the productioii of oxygen with, some- in aqueous solution, or that electron unnvailabilitv timrs, oxidative degradation. Certain features of a t thr carboxyl IS not the cause of benzenoid structure encourage inhibition w c h as the presence inhibition. The former idea i. supported by the of a double bond, a cycloalkyl group or an aromatic fact that the ionization constant of mesitoic acid is not much loner than t h l t of beiizoic acid, hoth in ring8 ncar the carboxyl group. If the published? mechanism is correct then ben- water a t 25' ; methyl electron-donation should rezenoid inhibition can be explained by an electron duce extent of proton loss Steric hindrance to deficieiicy a t the carboxyl group. Homver, Ham- carboxyl-and-ring planarity c m rcasoiiaI>ly acniett and Trefferss showed that when benzoic acid count for the lack of electronic tranqmission, but is compared with mesitoic arid aq the solute in requires a different explanation for the Hammett' pure sulfuric acid for freezing point lomring a t results. Perhaps the qteric hindrance would trnd high dilution, benzoic acid acquires a proton from to push off the hydroxyl group hut a t the same timc the solvent t o form two particles for every molecule prevent the carhouylate ion from getting close to . ___ the anode. ( 1 ) cknovlidgnxr~ntis nliidc t o thc Iixtional Sciencc 1'

Foiindntion, Contrart 3-0. C524-4. ( 2 ) 11. J. ..211(xn, O l g G n Z c Electrode Processes, Reinhold Pu1)lishing Corporntion, N e v York, 1058. pp 97-102. ( 3 ) F F1chtc.r and T. Holbro, H e k Phzn? Acta, 2 0 , (1 % 3 i ) .

(1)C I,. Wdson and IT.T. Lippincott, J . Amer. C h e m Soc., 78,4290 (1068).

( 5 ) H. P Treffrrs and Soc , 59, 1708 (lOJ7)

T, P.Hanimctt, J . Amer. Chem.



Received March 27, 1961 (6) C. W. Portrr and F. H. Thurhcr, J . .tmer. Chen?. SOC.,43, 1194 (1921).