6358
M. F. HAWTHORNE [A CONTRIBUTlON
FROM THE
DEPARTMENT OF CHEMISTRY
VOl. 76 OF IOWA
STATE COLLEGE]
The Question of Hydrogen Bonded Transition States in Nucleophilic Aromatic Substitution Reactions BY M. F. HAWTHORNE' RECEIVED JULY 21, 1954 The rates of reaction of o- and p-nitrochlorobenzene with piperidine have been measured and it was observed that substitution of deuterium for hydrogen on the amino group of the nucleophile did not alter these rates of reaction. The displacement of chloride ion from the ortho compound by piperidine a t 116' proceeds 80 times more rapidly than the similar reaction of the para compound. These results indicate that hydrogen bonding of amino hydrogen with the nitro group of o-nitrochlorobenzene probably does not exist in the transition state and thus cannot account for the greater reactivity of the ortho compound. An alternative explanation is presented.
Many previous kinetic studies of the nucleophilic displacement of halogen from compounds such as oand p-nitrochlorobenzenes (I and 11, respectively) indicate a striking inversion of relative reactivity of the ortho and para isomers when the attacking nucleophile is changed from alkoxide ions to primary or secondary amines2 Specifically, i t is always observed that the ortho-substituted substrate gives the greater rate of displacement with primary or secondary amines while the cara-substituted compound gives the greater rate with alkoxide ions. Bishop, Cave11 and Chapman3 have recently explained the greater reactivity of substrates such as 2-chloro-5-nitropyridine, 2-chloro-3-nitropyridine and 2,4-dinitrochlorobenzenetoward aniline than toward pyridine on the basis of the greater steric requirements of pyridine and the possible existence of hydrogen bonds in the transition states of the aniline reactions. This novel hydrogen bond hypothesis could possibly explain the occurrence of the rate inversion described above if hydrogen bonded transition states such as I11 do indeed exist in spite of the non-coplanarity of the o-nitro group with the benzene ring and the resulting loss of resonance stabilization in such structures. This paper records an experimental attempt to verify this hypothesis. GI, .
organic reactions which involve either the loosening4*5or complete breaking6 of carbon-hydrogen bonds in the rate-controlling transition states. Therefore, it seemed logical that the question under examination which involves the formation of a weak hydrogen bond in the transition state I11 could be similarly solved by the substitution of deuterium for hydrogen on the amino nitrogen. Unfortunately, little information is available with respect to the direction or magnitude of this isotope effect7 but it may be assumed to be generally small and with the deuterated hydrogen bond the most stable of the two in systems such as the one under consideration. In addition to this primary isotope effect another small secondary isotope effect may arise from the effect of N-deuterium substitution on the apparent nucleophilicity of the secondary amine utilized in the formation of 111. Such an effect would be formally similar to the rate-decreasing hyperconjugative isotope effect of Lewis and and would be a direct result of the decrease of the force constant of the N-H bond when the secondary amine undergoes the change (-1). R R \ \+ R--S
/
+ R-N-R /
H
H
(A)
Table I records the results of the kinetic experiments carried out with I and I1 using both normal and N-deuteropiperidines as the nucleophiles. The solvent chosen for these rate determinations was anhydrous xylene since this material possesses a relatively low vapor pressure, has no ability to hy(4) E . S . Lewis and C. E. Boozer, THISJ O U R N A L , 76, 791 (1954). ( 5 ) C . E. Boozer a n d E. S. Lewis, ibid.,76, 794 (1954). (6) M . Cohen and F. H. Westheimer, ibid , 74, 4387 (1952: (7) W. H. Claussen and J. H. Hildebrand, ibid., 66, 1820 (1931), found t h a t D F has a slightly higher vapor pressure t h a n H F . Later. R . W. Long, J H. Hildebrand and \V.E. Morrell, i b i d . , 6 6 , 182 (1943). observed t h a t t h e F-D-F bond is 5 0 cal./mole more stahle t h a n t h e
R' 111
Results and Discussion The substitution of deuterium for hydrogen has previously been of great value in kinetic studies of (1) Iowa State College Research associate, 1953-1954. Present address, Rohm and H a a s Company, Redstone Arsenal Research Divi. sion, Huntsville, Alabama. ( 2 ) See J. F. Bunnett and R . E. Zahler, Chem. R e x . , 49, 304 (1951), f o r numerous examples of this rate inversion. (3) R. R . Bishop, E A S. C a v e l l a n d N . R . Chapman, J Chem S o c . , 497 ( 1 ~ 8 ) .
F-H-F bond in (DF'Ie and (HF)a, respectively. This xork taken along with t h a t of G. N. Lewis a n d P. W. Schutz, ibtd , 5 6 , 4'33, 1002, 1913 (1934), on t h e vapor pressure differences of associated and n ' m associated substances when deuterated ( i e , D~carliqxL-aretic a c i d , DCL and DCN) indicate t h a t t h e deuterium b o n d i$ s!ij,li:ly niore stable t h a n t h e corresponding hydrogen b m d Tiir a(lditionLLle x amples see L N. Ferguson. "E!ectron Structures ,if Oryanic Rfi,lecules," Prentice-Hall Inc. S e w York, N Y , F ,i7. Crystal s t r u c l i i r e studies have a13n s h o n n isotope effects when t!ie crystal Inltice contains hydrogen honds a n d deutesium is sul)stituted f
