Oct. 20, 1959
COMMUNICATIONS TO THE EDITOR
5509
basis in animals. It also reduces K + excretion as a n analogous mechanism for aromatic hydrogen compared to C1- excretion. exchange would involve a slow proton transfer Chlorosulfonation and amination of 5-chloro-o- (-423~2reaction), a reaction whose acidity dependacetotoluide (111) yielded 5-chloro-4-sulfamyl-o- ence is not known with ~ e r t a i n t y . ~Since there acetotoluide (IV) (n1.p. >263’; Anal. Calcd, for is no reason to consider hydrogen fundamentally CSHiiNZ03SCl: C, 41.1; H , 4.20; S , 10.6; S, different from other electrophilic reagents, i t seems 12.2; C1, 13.5. Found: C, 41.0; H, 4.31; N, desirable to re-examine the mechanism of aromatic 10.6; S, 11.9; C1, 13.8)which was oxidized with hydrogen exchange to see whether i t is not, in KMnO4 to N-acetyl-4-chloro-5-sulfamylanthranilic fact, an A-SE2 reaction. acid (V) (m.p. 254-256’; -1nal. Calcd, for CgHsNtThe -1-1 reaction can be distinguished from the O5sc1: C, 36.9; H, 3.08; N, 9.5’7; S, 11.0; C1, x - s E 2 reaction by the form of its acid catalysis: 12.1. Found: C, 37.3; H, 3.60; K j 9.92; S, The A-1 reaction is catalyzed only by hydronium 10.7; C1, 12.3). Treatment of V with urethan a t ion, whereas the A - S E ~ reaction shows general acid 180-190’gave I (R = CHa) directly (m.p. >320’; c a t a l y ~ i s . ~This difference cannot be observed .4nal. Calcd, for C9HYN303SC1: C, 39.6; H, with the usual aromatic substrates because these 2.93; N, 15.3; S, 11.7; C1, 13.0. Found: C, react a t appreciable rates only in strong mineral 39.3; H, 3.23; N, 15.2; S,11.5; C1, 12.9). Al- acids. The accelerating influence of a methoxy ternately, V was hydrolyzed to l-chloro-5-sul- group on this reaction is, however, very strong, famylanthranilic acid VI (m.p. 275”; Anal. Calcd. and a prediction based on known partial rate for C7H7NzO4SC1: C! 33.5; H , 2.79; N, 11.2; factors6 leads to the expectation of measurable S, 12.8; C1, 1-12. Found: C, 33.3; H, 2.85; S , rates in dilute aqueous acid for molecules bearing a 11.1; S, 12.6; C1, 14.1) which on fusion with form- sufficient number of suitably arranged methoxy amide a t 170-173’ gave I (R = H) (m.p. 310- groups. This prediction is borne out by experi315’; -4nal. Calcd. for CsH6N303SCl: C, 37.0; ment: 1,3,5-trimethoxybenzene-2-thas an exH, 2.31; N , 16.2; S, 12.3; C1, 13.7. Found: change half-life of approximately 30 minutes in C,37.1; H , 2.60; N, 15.5; S,12.4; C1, 13.6). 0.05 N strong acid. The rate of exchange is Reduction of the 4(3H)-quinazolinones (I) proportional to the first power of hydronium ion with KaBH4 in the presence of A41C13gave highly concentration over the range 1.3 X to 5 X active compounds of the 1,2,3,4-tetrahydr0-4N . In buffers, a t constant hydronium ion quinazolinone structure ( I I ) , for example; 7- concentration, the rate is also proportional to chloro - 6 - sulfamyl - 1,2,3,4 - tetrahydro - 4 - buffer concentration; Fig. 1 shows that rate changes quinazolinone (11, R = H ) (m.p. 256-258’; by a factor of 3.5 with a change of 10 in acetate A n d Calcd. for CsHsN303SC1: C, 36.7; H, -3.06; N , 16.1; S, 12.3. Found: C, 37.2; H, 6 0 1 I 3.30; X, 16.2; S, 12.2) and i-chloro-2-methyl-6sulfamyl-1,2,3,4-tetrahydro-4-quinazolinone (11, R = CH3) (m.p. 275’; Anal. Calcd. for CgH1003NaSCl: C, 39.2; H, 3.63; Ti> 15.3; S, 11.7; C1, 12.9. Found: C, 39.1; H, 3.60; S , 15.1; S, 11.8; C1, 12.7). A number of other compounds in this series have been prepared and will be reported a t a later date ORGANIC CHEMICAL RESEARCH SECTIOX x 3.0 ;/
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LEDERLELABORATORIES DIVISION ELLIOTT COHEK BETTYKLARBERC AMERICASC Y A S A M I D C O M P A h T YORK JAMES R. I.AUGHAS,JR. PEARLRIVER,SEW RECEIVED Au:~.sT 19, 19Fi9 T H E MECHANISM OF ACID-CATALYZED AROMATIC HYDROGEN EXCHANGE’
I
.o I.
I
Because rates of aromatic hydrogen exchange in L--I strong aqueous acid are proportional to Ham0 0 05 0 10 mett’s acidity function, / I ,, this reaction is thought M HOAc to proceed by the -4-1 mechanism,? which, in this Pig 1 -Dependence of rate of nuclear h! drogen exchange case, demands a reaction sequence of a t least three steps. The evidence for all other electrophilic 111 1,3,5-trlmethnsybenzene rm acetate buffer concentratirm aromatic substitutions. however. demands nothing d t constant hydroniurn inn concentration more complex than a two-step reaction ~ e q u e n c e . ~ ~
_I_
(1) Work performed under t h e auspices nf the U S .4tomlc Energy Commission, (2) V. Gold and D . P.N Satchell. .I f‘hi,ni .Sot., B609, 8619, 3622 (1955); 1635 (1956). 13) L . Melander, .4Yki.J Kemr, 2 , 211 (lY50), C K. Ingold, “Structure and Mechanism in Organic Chemistry,” Cornell University Press, l t h a c a , 9.Y . , 1953. p. 279; P U’, Robertson, J . Chew. S o r . , 1267 (1954); P. B. D. de la hIare, ’I’11. D u n n and J . T. Harvey, ibid., Y23 (1957): H. Zollinger, E x p e v z e x f i a , 12, 163 (1956); A. J. Kresge,
unpublished work on mercuration; A. J. Kresge and D P. N Satchell, Tetrahedron. in press. (4) F. A. Long and M. A. Paul, Chem. Reos., 67, 942 (1’257); A. J . Kresge a n d D. P. N. Satchell, Chem. and Ind., 1328 (1968); L. Melander and P. C. Myhre, Avkiv Kemi, 1 3 , 507 (1959). ( 5 ) R. P. Bell, “Acid-Base Catalysis,” Oxford University Press, London, 1941, p . 124; A. A. Frost a n d R . G. Pearson. “Kinetics and Mechanism,” John Wiley a n d Sons, Inc., New York, N. Y . , 1953, p. 20-1; F. A. Long and M. A . Paul, Chem. Revs., 67, 943 (1957). ( 6 ) D. P. N Satchell, J . Chetn. SOC.,3911 (1956).
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COMMUNICATIONS TO THE EDITOR
buffer concentration a t constant ionic strength ( f i = 0.100, [HOA4c]/[OAc-] = 1.00). No exchange was observed in sodium hydroxide solution during the time required for complete exchange i n acid a t a hydronium ion concentration comparable to the hydroxide ion concentration. Since acetate ion is a much weaker base than hydroxide ion, the dependence of rate on buffer concentration must be the result of catalysis by acetic acid and not by acetate ion. Preliminary results with other acids indicate compliance with the Bronsted relation; a is near 0.5. This evidence indicates that, in the rate-determining transition state for aromatic hydrogen exchange catalyzed by weak acids, the proton is not yet completely transferred from acid anion to aromatic. This reaction, therefore, must be a slow proton transfer, and the mechanism can be described quite simply as
which on acidfication gave y-tropolone. Photoy-tropolone methyl ether (I) is quantitatively converted to y-tropolone methyl ether (Ilb) after 110 minutes in 0.0857 N sodium hydroxide a t 22'. This rapid reaction is in dramatic contrast to the acid-catalyzed opening of I to IIa which does not proceed a t a measurable rate in 0.095 N sulfuric acid a t 22' and which is only 27% complete after 5 hours a t 80' in the same acid con~entration.~ The base-catalyzed isomerization of photo- y-tropolone methyl ether to I I b is without precedent. The facility of this reaction is no less than astonishing. The base-catalyzed reaction fails for dihydro- and tetrahydrophoto-y-tropolonemethyl ether which, however, do undergo acid-catalyzed ring opening.' The isomerization of I to I I b can be induced by bases weaker than hydroxide, but the rate is very considerably reduced. Prolonged refluxing of I in 95% ethanol also effects the conversion of I to IIb. Iodide ion does not catalyze H'Ar + HA H'H,4rf + A the transformation of I to IIb. H'HAr+ + A HAr + H'A The transformation of I to I I b is best rationalized iVe are grateful to hZr. R. P. Bell, F.RS., for on the basis of attack by hydroxide ion on the his interest in this work. cyclobutene double bond leading to the anion DEPARTMEVT OF CHEMISTRY A . J KRESCE I11 which can collapse quite simply to IIb. The BROOKHAVEN SATIOXAL LABORATORY Y P T O N , LOXGISLAND, YTEW YORK Y. CHIAKG Michael-type addition depicted is, to the best of our knowledge, without precedent. Interaction RECEIVED AUGUST18, 1939
=
OhIe
HO
A NOVEL BASE-CATALYZED ISOMERIZATION OF A BICYCLIC SYSTEM TO A TROPONOID SYSTEM
LN-0.
- A'
Siu:
L:
In the course of experiments designed to test the feasibility of anion formation a t the bridgehead of photo- y-tropolone methyl ether (I)' (by basecatalyzed exchange of hydrogen for deuterium) i t was found that I was rapidly and completely destroyed by 2 N aqueous sodium hydroxide with the production of a highly water soluble acidic product. The acidic product was identified quickly as y-tropolone (Ira) by its characteristic ultra-
RIeO
I
Ha. I1 = l I b, R =,\le
0
110
3 -
.ill,
"OAk
between the non-con jugated double bond and the cyclopentenone system is evident in the ultraviolet spectrum (243 mp) of I. Acknowledgment.-The authors wish to acknowledge financial support of this investigation by the Research Corporation through a Frederick Gardner Cottrell grant and by a research grant (CY-4253 PET) from the Cancer DiLrision of the National Institutes of Health, Public Health Service.
violet spectra in iicutral solution2 and in 0.1 N sodium hydroxide.2 In dilute base (O.OSS7 A' h e hydrolysis of -(-troiwlonc methyl etlirr in 0.0!13 A' s u l f u r i c sodium hydroxide) Lhe product initially observed acid( 5 )a tT80' is cluite rapid and y-tropoione is thus the observed p r o d u c i is y-tropolone methyl ether (Ilb, Amax 223 nip (unimblished rate measurements 0 . I,. Chal,man wnd D . J . Pasto) (19,700) and 333 m p (13,000) in aqueous solutionY DEPARTMEST OB CHEMISTRY and in 0.1 N sodium hydroxide3). Brief warming IOWASTATEUNIVERSITY 0 . I,. ~ i 1 A I ' ~ l A X D. J . P A S ' i . 0 of the basic solution gave y-tropolone anion4 AMES, ion-^ RECEIVED A4uc:v~,r 2 7 , 105!1
(1) 0. I,. Chapman and D. J. Pasto, THIS JOURNAL,80, 6685 ( 10x4).
(2) I n methanol y-tropolone shows A,, 228 m r (4.27) and 337 m r ( 1 . 1 1 ) a n d i n O . l S s o d i t i m hydroxide227 mp ( *.30)and 3 l j O mp ( 4 . 3 3 ) ; '1'. S o m e , 1'. Mukai. Y . Ikegami and T. Toda, Chem. a n d Ind., fifi (1925); K.B. Johns, R . S. Coffeyand A. W. Johnson, ibid., 8.58 (1955); J . hfeinwald and 0. L. Chapman, THIS J O U R N A L 78, , 4816 (1956). ( 3 ) Authentic ytropolone methyl ether shows exactly this spectrum i n either water or 0.1 r\i sodium hydroxide. ( % )This was recognized by its characteristic ultraviolet spectrum.2 T h e hydrolysis of y-tropolone methyl ether does not proceed a t a significant r a t e in 0.0887 h' sodium hydroxide a t 2 2 O , b u t in t h e same concentration of base a t SOo i t is quite rapid (unpublished r a t e measurements of 0. L. Chapman and D. J. Pasto).
COLINEAR BONDS AT THE OXYGEN ATOM S i r:
Colinear bonds a t the oxygen atom wcre fouiid first in 19% by G. R . Levi and G. Peyronel' in the pyrophosphate anion, and more recently in H3Si-O-SiHs2 and in the (C15RuORuClj)--I an(1) G. R. Levi and G. Peyronel, Z . K r i s l . , 9 2 , 190 (1936). (2) R . C . Lord, D. W.Robinson and W. C. Schumh, THISJ O ~ R N A L .
78, 1327 (1956).
