7458
Intermediates in Nucleophilic Aromatic Substitution. XIV. 1 Spiro Meisenheimer Complexes Derived from N,N’- Dimethylethylenediamine. Kinetics in Aqueous Dimethyl Sulfoxide Claude F. Bernasconi*za and Francois Terrierzb Contribution from the Thimann Laboratories of the Uniuersity of California, Santa Cruz, California 95064. Received May 5 , I975
Abstract: The rates of the equilibrium formation of the spiro Meisenheimer complexes derived from N,N’-dimethyl-N-(2,6dinitro-4-trifluoromethylphenyl)ethylenediamine( 2 ) in 70% MezSO-30% water and from N.N’-dimethyl-N-(2,4-dinitropheny1)ethylenediamine (3) in 70% MezSO-30% water and 80% Me2SO-20% water have been measured. Proton transfer is rate limiting at low buffer concentrations and low pH and partially rate limiting at high buffer concentrations and/or high pH. While protonation of the anionic form of the complex by H30’ is diffusion controlled, the rate of deprotonation of the zwitterionic form of the complex by OH- is two to three orders of magnitude lower than diffusion controlled, indicating intramolecular hydrogen bonding in the zwitterion. The low values of the proton transfer rates between the buffer components and the complexes lead to the same conclusion. Previous inferences which led to a reconsideration of current notions about the mechanism of base catalysis in nucleophilic aromatic substitutions by amines are reenforced by the present study.
A recent study3 of the reversible formation of 1 in aqueous solution has shown that the reaction can be described by
n
CHJN NCHj “ N - = p =.--””’
n
”-cj-” . CH,N
NCH,
_’
dF
NO. 1
o-‘”; n
CH3N
NCHJ
.--’ NO,
j
2
3
Scheme I. The reaction was strongly buffer catalyzed a t p H 19.5 with a curvilinear dependence on buffer concentration leveling off a t high concentration. The interpretation was that below p H 9.5 and at low buffer concentrations, the proton transfer, X H e X-, is slow compared with the step AH XH; i.e., k - l > k3’, k-3’ with
-
+ k3OH[0H-] + k 3 B ~ [ B r ] ( 1 ) k-3[H+] + k - 3 0 H + 2 I ~ - ~ ~ I [ B H , (2) ]
k3’ = k3
r=l n
k-3’
I = I
where k3, k30H, and k3Bg refer to the deprotonation of X H by the solvent, by OH-, and by any general base (buffer, A H , X-), respectively, and k-3, k-30H, k-3B~refer to the protonation of X - by H 3 0 f , by the solvent, and by any general acid (buffer, AH2+), respectively. In this paper, we report a similar study for the two complexes 2 and 3. The lower stability of these complexes necessitated a change of solvent to 70% MezSO-30% water (v/v) and 80% Me2SO-20% water (v/v). In general our results confirm the conclusions reached with 1, but they reveal some new features as well In particular we report, apparently for the first time, rates of proton transfers in aqueous Me2SO. W e also present kinetic evidence of intramolecular hydrogen bonding to the o-nitro group in the zwitterionic form ( X H ) . The relevance of our results to the mechanism of base catalysis in nucleophilic aromatic substitutions by amines will be pointed out.
to their solution in 70% or 80% Me2SO. This is evident from Figures 1 and 2. The kinetics of equilibration between the various species of Scheme I was studied over a wide p H range (see Tables 1-111). At low pH, buffered solutions were employed while, in strongly basic solutions, tetramethylammonium hydroxide was used; the ionic strength was always kept constant a t 0.5 M by adding tetramethylammonium chloride as needed. The kinetic data were all obtained under pseudo-firstorder conditions, at 20°. At the lower end of the p H range, the relaxation time (T) was relatively shortest in the more concentrated buffer solutions and only measurable by the temperature-jump t e ~ h n i q u e At . ~ high pH, the equilibrium favors X- (and X H ) over A H (and AH*+) to such an extent that the relaxation amplitude becomes too small for accurate measurements by the temperature-jump method. However, here the relaxation time is longer and within reach of the stopped-flow t e c h n i q ~ e . ~ Rate Equations. Arguments similar to those presented earlier3 show that the rate equation developed for 1 in aqueous solution can also be used here. Thus for the reciprocal relaxation time. we have
k l (k3 T-I
+ k30H[OH-] + 2 k3B‘[Bi]) I=
=
I
+ k3 + k3OH[0H-] + r5 k3Bi[Bl] =l
k-1
KA
K A + [H+I
k-1 (k-3[HC]
t
+ k-30H + 5 k-3Bi[BH,] I=
k-1
X
I
+ k3 + k30H[OH-] + 2 k3Bi[B,]
(3)
1=1
Three special cases are of particular interest. I. When the concentration of at least one of the B,’s (usually the buffer base) and/or of OH- is high so that k3 k30H[OH-] + Zk3Bi[B,]>> k - I , eq 3 becomes
+
Results General Features. N.N’-Dimethyl-N-(2,6-dinitro-4-trifluoromethy1phenyl)ethylenediamine and N,N’-dimethylN-(2,4-dinitrophenyl)ethylenediamineare rapidly convertwhere K x is the acid dissociation constant of X H (“hi” in ed to the respective complexes 2 and 3 when base is added T h i stands for “high buffer concentration”). Experimentally Journal o j t h e American Chemical Society j 97:26 j December 24, I975
7459 Scheme I
+
HC CH2CHlNH2CH, \ /
”’
I
,CH2CH,NHCHJ
H ‘C,
I
’N‘
I
I
Q
k
i A-I
s
S
AH
AH,+
s
s XH
X400
this situation manifests itself in the leveling off of a 7-I vs. [Bi] plot. 11. When the concentration of all the Bi’s is zero, we have eq 5 k i ( k 3 + k3OH[OH-1) KA Tno-l = k-1 k3 k30H[OH-] KA [H’]
+ +
+
+
500
600
nm
Figure I . Absorption spectra of N,N’-dimethyl-N-(2,6-dinitro-4-trifluoromethylpheny1)ethylenediaminehydrochloride at various pH’s (buffer solutions) and in strong base, in 70% MezSO-30% water (v/v); [AHl+]o = 3.52 X M .Note that the irregularitiesbelow 400 nm are due to some absorption by the buffers.
08
(“no” in T , ~ - stands ~ for “no buffer”). This corresponds to the intercepts of plots of 7-l vs. buffer concentration, extrapolated to zero substrate concentration, or of plots of 7-l vs. substrate concentration, extrapolated to zero buffer concentration. 111. At low buffer concentration, plots of 7-’ vs. total buffer concentration, [ B ~ ] o ,a~r e linear because the k 3 B l [ B ~term6 ] in question is small and negligible compared with the other rate terms in the denominators of eq 3 . The initial slope of such plots is given by eq 6 where K B is~ the acid dissociation constant of BHI.
06 W
E 0 0
e n
04
a 02
slope = 300
400
600
500
nm
k-1
+ k3 + k30H[OH-] + r,f k3Bf[Br] =2
From eq 4 through 6 and some simplifications thereof, coupled with some equilibrium measurements, most rate constants characterizing Scheme I can be evaluated, as will be shown below. Kinetic and Equilibrium Measurements of 2 in 70% Me2SO. A representative plot of 7-l vs. buffer concentration is shown in Figure 3 for the o-bromophenol buffer at p H 10.58. At this and a t higher pH values, low substrate concentrations ( M ) could be used rendering substrate catalysis negligible. At pH 1 9 . 5 4 substantially higher substrate concentrations (up to 1.7 X M ) were necessary in order to achieve measurable complex concentrations. As a consequence, substrate catalysis became significant, particularly a t low buffer concentrations. Two typical plots are shown in Figure 4. From plots such as Figure 4, the contribution of substrate catalysis to 7-I was evaluated for any given run. It amounted typically to about 10% of 7-l or less. “Corrected” 7-I values, representing only buffer and O H - catalysis, were then calculated for use in plots of 7-I vs. buffer concentration. As is apparent from Figure 3 and was true a t all other pH values investigated, the buffer plots do not quite reach
Figure 2. Absorption spectra of N.N’-dimethyl-N-(2.4-dinitropheny1)ethylenediamine hydrochloride at various base (OH-) concentraM. tions, in 70% MezSO-30% water (v/v); [AH2+]o = 3.78 X
the plateau, in contrast to our findings for 1 in aqueous sol u t i o ~ - ~~ h. ~i - l can nevertheless be obtained from “inversion plots” as follows. From the very strong dependence on buffer concentration, it is obvious that, for moderate and high concentrations, we have k 3 B I [ B ~>> ] k3
+ k30H[OH-] + 2 k3Bi[Bi] i=2
and k - 3 B I [ B H ~ ]>> k-3[H+]
+ k-30H + ,=z,f k-3’l[BH,]
Thus eq 3 simplifies to
k- I ~ - ~ ~ ’ [ B H I ] (7) k-1 k3BI[B1]
+
which upon inversion and some arithmetic manipulation affords
Bernasconi. Terrier
/
Spiro Meisenhrinier Coniplexes
p-Cyanophenol
{ 1: 2
/,:i o-Bromophenol
(:I:
p-Chlorophenol
{ 1:1 : 3
Phenol
2: 1
{i;;
Benzimidazole
1:l { 3:
Indazole
c:;:
8.64 8.76 8.94 9.24 9.54 10.58 10.88 11.18 11.06 11.54 12.00 12.48 12.96 13.01 13.49 14.04 14.52 14.81 14.96 15.11 15.29 15.41 15.51 15.59 15.71 15.81 16.11
69 i 5 55 i 3 35.5 t 2.5 22 i 3 14 t 2 7 i 2 -2 =2 =2 =2 ~2.5 m2.5 ~2.5 =3 m2.5 -2 12 i 2 29.0 i 2.0 42.8 i 1.0 58.6 t 1.0 95.2 i 1.0 117 i 2 139 i 2 187 i 6 212 i 5 245 i 12 396 i 25
6.69 i 0.21 5.20 i 0.15 3.84 t 0.12 1.22 i 0.03 1.43 i 0.04 1.34 i 0.04 0.28 I0.01 0.52 i 0.02 0.25 i 0.01 0.52 i 0.02 0.82 i 0.03 0.49 i 0.02 0.83 i 0.03 0.24 i 0.01 0.59 t 0.02
4 0 0 0 0 i 6000 21000 i 2000 12500 i 1000 2860 i 300 2380 i 200 2000 i 100 1750
i
80
0.185 0.2 10 0.205 0.106 0.106 0.104 0.163
Q T ~ ~ equals - ' T-' extrapolated to zero buffer and zero substrate concentration. bFrom data obtained by the temperature-jump method at pH ~ 1 1 . 5 4from , data obtained by the stopped-flow method at pH 2 1 1.54. CInitial slope of 7-' vs. [B,] o. dReciprocal of intercept of plot according to eq 8 , from data obtained by the temperature-jump method. eCalculated from eq 9.
Table II.
Kinetics of 3 in 7070 Me,SO at 20" 1 0 - ~x slope,b.c M-l sec-'
Tno -I 1 a, b
Buffer p-Chlorophenol
2: 1
Phenol
t ti:
Benzimidazole
(2;1 : l
[Me,N+OH-]
/0.0005 0.001 0.002 0.003 0.005 0.010 0.020 0.030 0.050 0.100 0.200 0.250 0.400
I
UH
sec-l
11.84 12.00 12.48 13.01 13.49 13.71 14.81 15.11 15.41 15.59 15.81 16.11 16.41 16.59 16.81 17.11 17.41 17.51 17.71
oi1 0 t 0.5 0.4 i 0.2 0 ? 0.1 0.4 i 0.1 0.28 i 0.05 0.050 i 0.001 0.089 i 0.002 0.166 i 0.003 0.23 i 0.004 0.34 i 0.007 0.65 t 0.013 1.17 i 0.02 1.42 i 0.03 1.87 + 0.04 2.39 i 0.05 2.93 i 0.06 3.22 i 0.06 3.65 i 0.07
10.3 i 0.3 2.50 t 0.07 2.08 i 0.06 0.50 i 0.02 0.28 i 0.01 0.180 i 0.006
7hi-l,d
k-]/k,BI,e
sec-'
M
2550 i 300 1850 i 150 600 i 75 1 8 0 t 20 100 f 10 50 i 5
0.158 0.137 0.138 0.160 0.244 0.195
aSame as in Table I. bFrom data obtained by the stopped-flow method. C-eSame as in Table I
where [Bl]o is the total buffer concentration. Plots of T vs. [B,]"-l are in fact linear as can be seen for a representative e x a m p l ~in Figure 3. The intercept yields T h i , whereas the slope permits one to find k - l / k 3 B 1 according to k-l - slope K B ~ -(9) k3Bi Thi K e l -I- [ H ' ] Table I summarizes all 7 h i - I (eq 4) and T , ~ - I (eq 5) values as well as the initial slopes (eq 6) of the buffer plots, and k - 1 / k 3 ~ calculated I from eq 9. The acid dissociation constant of XH, Kx, and the product K A K ~could be determined by the same spectrophotometric procedure used b e f ~ r eA. ~plot according to eq I O Journal of the American Chemical Society
/
Y7:26
where O D is the optical density at the A,, (585 nm) of X-, I the path length, and C X H and tx- the molar extinction coefficients of XH and X-, respectively, is shown in Figure 5. Assuming ~ X H= tx- = 2.28 X lo4 (tx- determined a t high p H where all substrate is in the form of X-), we obtain K x = slope/intercept = 3.25 X M and K A K ~= intercept/tx- = 8.95 X M. Calculation of Rate Coefficients for 2 in 70% Me2SO. The various rate constants, summarized in Table IV, were calculated as follows. ( 1 ) A plot of T ~ , - I vs. [ H + ] is linear,
/ December
24. 1975
746 1 Table 111. Kinetics of 3 in 80% Me,SO at 20" Buffer o-Bromophenol p-Chlorophenol Phenol Phenol
[ Me,N+OH-]
a-e
3: 1 1: 1 1:3 1:1 0.0005 0.001 0.002 0.003 0.005 0.010 0.020 0.030 0.050 0.100 0.200 0.250
PH 11.91 12.44 12.96 13.56 16.59 16.89 17.19 17.37 17.59 17.89 18.19 18.37 18.59 18.89 19.19 19.29
7no-1,a, b sec-' -2 r 5 2 i 2 0.08 i 0.10 0.12 i 0.10 0.012 f 0.0002 0.044 i 0.0009 0.107 i 0.002 0.168 i 0.003 0.291 i 0.006 0.613 i 0.012 1.08 r 0.02 1.50 ? 0.03 2.12 r 0.04 2.88 i 0.06 3.80 r 0.08 4.15 i 0.08
10- x slope,btc sec-' 4.30 1.55 0.26 0.20
? ?
t t
sec-'
k-,lk,B1,e M
1000 r 200 330 r 70 100 t 20 5015
0.165 0.091 0.07 1 0.112
7hi-1,d
0.20 0.07 0.01 0.01
Same as in Table 11.
2000
1
1
I 1500
-
I
0
2~
0
[AH],
t
~ X I O - ~
M
Figure 4. Representative plots of 7-I vs. substrate concentration for 2 in 70% Me2SO: (0)p-cyanophenol, [ B I ] = ~ 1.2 X lo-* M ,pH 8.64; M ,pH 9.54. (0) p-cyanophenol, [ B I ] =~ 1.5 X Figure 3. Representative plot of 7-l vs. total buffer concentration for 2 in 70% Me2SO; o-bromophenol buffer, pH 10.58. (0) Inversion plot according to eq 8.
indicating K A >> [ H + ] (see eq 4). From its intercept, we obtain k~ = 1700 f 100 sec-i and from its slope, k - I / K x = 3.64 f 0.55 X lOI3 M - ' sec-I. In conjunction with K x determined spectrophotometrically, this yields k - l = l . 18 f 0.30 X IO6 sec-l and K I = k l 1 k - l = 1.44 f 0.50 X in combination with K A K ~measured spectrophotometrically, we also obtain K A = 6.3 f 1.5 X M or ~ K =A8.20 f 0.1. This value for K A is consistent with the linearity of the plot of 7 h i - l vs. [H+] since at pH >9.3 K A >> [H+], whereas a t pH 1 9 . 3 the kl term in eq 4 is negligible compared with the k-1 term. (2) At pH 19.54, a plot of T , , ~ - I vs. [ H + ] is linear. At these pH values, the equilibrium strongly favors AH2+ and AH over X H and X- so that the first term in eq 5 is negligible. Furthermore k-1 >> k 3 0 H [ O H - ] k3 even if the highest possible values for k30H (=2 X 1OIo M-l sec-I) and for k3 ( k 3 = k-3Kx = 5 X 10'OKx = 1.6 X lo3) are assumed; hence eq 5 reduces to
+
-
0 0
2
6
4
X
8
[H+]-', M-'
Figure 5. Determination of K x and K I K A for 2 in 70% Me2SO; plot according to eq 10.
k - 3 [ H + ] , k 3 0 H [ O H - ] >> k3, and K A k-1 >> k3, eq 5 now reduces to
>> [H+]; since
also
+
= k-3[H+] k-30H (11)' From the slope, we obtain k-3 = 2.86 f 0.50 X 1 O l o M-I sec-I; this also allows calculation of k3 = K x k - 3 = 9.3 f 2.5 X lo2 sec-I. The intercept ( k - 3 0 H ) is too small for an accurate evaluation of k - 3 0 H . (3) In strongly basic solutions (pH 214.8), k-30H >>
As long as k-1
>> k 3 0 H [ O H - ]this further reduces to
T"0
-I
=k 1 k 3 0 H[OH-]
k-i
Bernasconi. Terrier
+ kV3OH
(13)
/ Spiro Meisenheimer Complexes
7462 Table IV. Rate and Equilibrium Constants Obtained from
and
T~~
2 in 70% Me,SOb
1 in H,Oa
k-JKx, M-I sec-l k,, sec-l k- 1 , sec-' K, = k,/k-, Kx, M e PKXe k,OH,M-' sec-' k-,OH, sec-l k,, sec-l e k-3, M-I sec-l KA, M PKA KS
Thi
3.64 i 0.55 x lo1, 1.7 ~t0.2 x 103 1.18 i 0.30 x l o 6 1.44 t 0.50 x 3.25 i 0.30 x 10-*f 7.49 i 0.04.f 4.2 + 1.5 x l o 7 1.0 k 0.4 x 10-3 9.3 i 2.5 x l o 2 2.86 i 0.50 x 10" 6.30 i 1.50 x 8.20 k 0.10 7.85 x 1o-l9i
1.20 x 103 1.93 X l o s 6.21 x 10-3 2.29 x 10-7 6.64 5.2 x 109 4.45 x 102 1.35 x 104 5.9 x 1 O ' O 2.23 x 10-9 8.65 1.96 x 10-14
3 in 70% Me,SOb
3 in 80% Me2SOb
1.8 t 0.2 x 1015 4.0 i 0.5 2.4 t 0.2 x 106C 1.7 i 0.4 x C 1.33 i 0.30 X 10-9C~g 8.87 i 0.05C.g 4.2 X 1 O ' C 2.5 i 0.8 x 10-2cjh 38i 2.86 x 10'Oi
8.5 i 1.5 x 1014 6.25 i 0.40 4.3 i 0.6 x ioSd (4.3 x 1 0 6 ) ~ 1.47 i 0.35 x lO-'d (1.47 x 10-6)C 5 k 2 X 1O-Iod8g(5 x 10-9)c.g 9.3 k 0.2dvg (8.3)ng 4.2 X 106d (4.2 X 1 O ' ) C 1.04 t 0.30 x 10-4CJ1z 14.3d , i (143)Cr i 2.86 X 10'Oi
7.85 x 1o-l9i
1.29 x io-20i
25", p = 0.5 M maintained by NaCl (ref 3). b At 20", p = 0.5 M maintained by Me,NC1 (this work). C Assuming k,OH = 4 X l o 7 as for 2; see text. d Assuming k30H = 4.2 X lo6, reduced tenfold from 70% Me,SO due to hydrogen bonding; see text. eNot statistically corrected. f Determined spectrophotometrically. gDetermined from k-,/Kx. hcalculated as k-,OH = k30HKS/KX. iAssuming k-, = 2.86 X 1 O 1 O as for 2; see text. i S e e Experimental Section. a At
to 2.5 X M , a plot In the range of [OH-] = 5 X of Trio-' vs. [OH-] is in fact linear; the slope provides k 1 k 3 O ~ l k - l= 5.7 f 0.3 X lo4 M - ' sec-I. The intercept, k-30H, is again too small and uncertain. M , a plot of T,,-I vs. [OH-] beAt [OH-] L 2.5 X comes curved. An "inversion plot" according to eq 14
(note that the second term of eq 12 has been omitted in taking the inverse because it becomes negligible a t these base concentrations) is linear. The reciprocal of its intercept provides kl = 1670 f 300 sec-', in excellent agreement with the value of 1700 obtained from 7 h i - I . The reciprocal slope provides k 1 k 3 O ~ l k - l= 6.2 f 0.2 X IO4 M-' sec-' which compares well with the same quantity (5.7 f 0.3 X lo4) obtained via eq 13. In conjunction with k-1 and k l , we now find kjoH = 4.2 f 1.5 X lo7 M-l sec-l and k-30H = k30H K s l K x = 1.0 f 0.4 X sec-I, where K s is the self-ionization constant of the solvent. (4) If the values summarized in Table IV are substituted into eq 5 for the pH range 11 to 14, the only significant term is T
~
=~kl k3/k~
(15)
1
With k l , k3, and k-1 from Table IV, eq 15 predicts 7,,-l = 1.34 f 0.70 sec-'. This is consistent with our observation that T,,-' is in fact constant in this range, with an approximate value of 2.5 sec-I. In view of the difficulty in determining accurately (small intercepts of buffer plots), the agreement between the two numbers is very good indeed. (5) The proton transfer rate constants k3Bl and k-3BI for the buffers were calculated from eq 16 KR-
+
which is obtained from eq 6 after replacing k-3BI with k 3 B 1 K ~ , /and K ~ neglecting
k3
+ k 3 0 H [ O H - ]+ i2 k3Bi[Bi] =2
/
97:26
Discussion Reliability of Data Analysis. Ion pairing of buffer base or O H - with the tetramethylammonium ion and association of the type BHI B I - e BHI . . . B I - are possible features which in principle could lead to a distortion of our data. For example, the curvature in the buffer plots (Figure 3) could arise from such phenomena rather than from a change in the rate-limiting step of the mechanism. By working at constant ionic strength, ion pairing, if significant at all, should,
+
which is small compared with k-1. Average values from different pH solutions are summarized in Table V. I n some cases, k3Bl could also be calculated from the k-I/k3Bi values (eq 9); they are included in Table V. The agreement Journal of the American Chemical Society
between the numbers obtained from the two methods is excellent. Kinetics of 3 in 70% and 80% MQSO. Plots of 7-I vs. buffer and vs. substrate concentration, respectively, and of 7-l vs. [OH-] at high pH are qualitatively very similar to those for 2. Tables I1 and 111 summarize our results which were obtained by the same procedures as for 2. Due to a lower complex stability, no data below pH 11.84 could be obtained with reasonable accuracy; this also precluded a spectrophotometric determination of K x . The rate and equilibrium constants summarized in Tables IV and V were calculated in the same manner as for 2 except for the following variations. ( I ) The intercepts ( k l ) of the plots of 7hi-I vs. [ H + ] are very small and thus give only approximate values, k I = 10 f 5 sec-' in 70% Me2S0, kl = 12 f 5 sec-' in 80% Me2SO; kl could, however, be obtained more accurately from inversion plots according to eq 14 at high pH, and it is these values which are reported in Table IV. (2) It was difficult to get accurate data on Tn0-l in the buffered solutions because of very strong buffer dependence which leads to small intercepts. Hence plots of T , , , - ~ vs. [H'] according to eq 11 are merely scatter diagrams, and k-3 cannot be determined at all. We assume that k-3 is the same as for 2; this is doubtless a very good assumption in 70% MezSO and probably also in 80% Me2SO (see Discussion). (3) Because K x cannot be determined directly, neither can k-1 nor k30H;the values given in Table IV were calculated based on the hypothesis that, in 70% Me2S0, k30H is the same as for 2, in 80% Me2SO tenfold smaller than in 70% Me2SO. With these assumptions, to be analyzed in the Discussion, k-l is calculated from the slope of the plot of T~,-I vs. [OH-], eq 13 (or T , , vs. [OH-]-', eq 14). This, in turn, allows calculation of K x from k - l / K x which is the slope of ~ h i - l vs. [H']. Note that an over- or underestimation of k30H leads to a proportional over- or underestimation in k-I, in K x as well as in k 3 B ~but , leaves k-30H and k - 3 B Hunaffected. ~
/ December 24, I975
7463 Table V. Proton Transfer Rates for XH + B, e X- + BH,
x k,B1
7.49 7.49 7.49 7.49 7.49 7.49
APK = PKB, - PKx A. 2 in 70% Me,SO 1.75 3.09 4.05 4.99 5.52 7.03
5.7c (5.9)4 10.2d (11.2)s 6.9e (7.2)9 7.3f 7.28 7.5h
1.0 x 8.3 x 6.1 X 7.4 x 2.2 x 7.0 X
11.54 12.48 13.01
8.871' 8.87" 8.87i
B. 3 in 70% Me,SO 2.67i 3.61i 4.14i
14.9Li (15.2)9 14.9Lk (17.5)'4 ll.Oi9~(11.9)9
3.2 x 104 3.7 x 103 1.1 x 1 0 3
o-Bromophenol
11.43
p-Chlorophenol
12.44
Phenol
13.56
9.3m (8.3)" 9.3m (8.3)n 9.3m (8.3)"
C. 3 in 80% Me,SO 2.1m (3.1)" 3 1m (4.1)" 4.3m (5.3)"
BHl
pKBi
PKX
p-Cyanophenol o-Bromophenol p-Chlorophenol Phenol Benzimidazole Indazole
9.24 10.58 11.54 12.48 13.01 14.52
p-Chlorophenol Phenol Benzimidazole
M-l
sec-I
k-3B1, b IT' sec-'
___-.
2.44m,o (2.61)m,9 [24.4] 4.00m.o (4.73)m,9 140.01 " 4.45m,p ( 4 . 7 3 p 9 [44.5]
1.8 X li.8 x 2.9 x [2.9 x 2.5 X [2.5 X
io5 10' 10'
10' 10' lo-'
lo4 1041 103 1031
10' 10'1
From eq 16. bk_,B, = k3B1KB/KX. CAverage from three slopes: 5.91 X l o 6 (PH 8.941, 5.82 X l o 6 (PH 9.24), 5.44 X l o 6 (pH 9.54). dAverage from three slopes: 1.01 x l o 7 (pH 10.58), 1.06 x l o 7 (pH 10.88), 0.99 X l o 7 (pH 11.18). e Average from two slopes: 6.6.X lo6 (PH 11.06), 6.8 X l o 6 (pH 11.54). f Average from three slopes: 6.95 X l o 6 (PH 12.00), 7.32 X l o 6 (PH 12.481, 7.60 X l o 6 (PH 12.96). g Average from two slopes: 6.8 x 106 (pH 13.01), 7.7 x lo6 (pH 13.49). h Average from two slopes: 6.7 X l o 6 (pH 14.04), 8.2 X l o 6 (pH 14.52). i K x and k _ , obtained by assuming k30H = 4.2 X l o 7 as for 2. j From one slope only. k Average from two slopes: 1.32 X l o 7 (pH 12.00), 1.66 X l o 7 (pH 12.48). [Average from three slopes: 1.34 X l o 7 (pH 13.01). 0.9 X l o 7 (pH 13.49), 1.05 X 10' (pH 13.71). K X and k., obtained by assuming k,OH = 4.2 x lo6, reduced tenfold from 70% Me,SO due to hydrogen bonding; see text. K X and k _ , obtained by assuming k,OH = 4.2 x l o 7 as for 2 in 70% Me,SO. 0 From one slope only. P Average from two slopes: 5.5 X l o 6 (pH 12.96), 3.41 X l o 6 (pH 13.56). 9 F r o m k _ ,/k3B1. Q
however, be independent of buffer concentration and hence should not affect the curvature of these plots. That association between buffer base and buffer acid' is not significant, at least in 70% Me*SO, can be inferred from a number of observations. ( I ) The pH values of solutions made up of buffers in the [ B I ] : [ B H I ]ratios 1:3, I : ] , and 3:l differ by the theoretical amount of 0.48 unit up to the highest concentrations used in this study. (2) The same value for kl is obtained from data points collected at high buffer concentrations ( k l = intercept of plot of 7hi-l vs. [H+]) and those collected in the absence of any buffer (eq 14). We also note that k l k 3 ° H / k - ~ determined at low [OH-] (eq 13) is about the same as that determined at high [OH-] (eq 14), showing the reliability of our data treatment in basic solutions as well. (3) Where such a comparison is possible, the k - l / k 3 B 1 values (Tables I-111), for any given buffer system, are independent of the buffer ratio within the experimental error;* this is significant because k-l/k3BI was obtained at high buffer concentrations where association would be most pronounced. Furthermore, k3Bl values calculated from initial slopes, Le., from data at low buffer concentrations, are in excellent agreement with those calculated from k-l/k3BI (data at high buffer concentrations), again demonstrating the consistency of our analysis. I n 80% MezSO, the situation is a little less clear cut. The pH intervals for various buffer ratios are slightly dependent on buffer concentration, indicating some association. On the other hand, the close agreement between the k3BI values obtained at low and at high buffer concentrations again indicates that our analysis is basically sound; association thus seems to have a negligible effect on our results even in 80% Me2SO. Effects of Structure and Solvent on k l , k-1, and K , . Based on numerous analogies,y.10one expects, for a given solvent, kl and K I to decrease in the order 1 > 2 > 3 and k - I to increase in the order 1 < 2 < 3. For example, in the case of methoxide ion attack on the respective anisoles to
form the 1 , I complex in methanol, one has kl = 4.0 M-I sec-I, k-l = 5 X sec-I, and Ki = 7700 M-I for 2,4,6-trinitroani~oIe,~l kl 0.4 M-l sec-I, k-1 = 5.3 sec-' and K I 0.07 for 2,6-dinitr0-4-trifluoromethylanis0le." and kl = 2.12 X M-I sec-I, k-1 = 42 sec-I, and K I = 5.06 X for 2,4-dinitroani~ole.l~.'~ On the other hand, adding Me2SO to a protic solvent has the effect of increasing kl and K I . and of decreasing k - I The qualitative picture emerging from Table I V is entirely consistent with these expectations. Thus, despite the lower temperature, the change from water to 70% Me2SO apparently slightly overcompensates the expected decrease in kl caused by substituting a 4-nitro group with a 4-trifluoromethyl group. On the other hand, k-1 is about sixfold larger for 2 compared with that for 1; i.e., the change in solvent does not fully compensate for the change in structure. The above effects are not unexpected on the basis of the anisole-MeO- reactions since there the replacement of the 4nitro group with a 4-trifluoromethyl group lowers the kl only about tenfold but increases k-1 about 104-fold. I n fact, based on this comparison, one might have expected that k-1 for 2 in 70% Me2SO is more than sixfold larger than for 1 in water. Intramolecular hydrogen bonding to the o-nitro group, for which evidence is presented below, may be responsible for the low value of k-1 since the activation energy of the k-1 process would have to include the energy required to break this hydrogen bond. In comparing 2 and 3 in 70% Me2S0, we note that k I for 3 is 425-fold smaller than for 2, while k-1 for 3 is 2-fold larger than for 2. This compares rather closely with the anisoles where MeO- attack on 2,4-dinitroanisole is about 200 times slower but dissociation about 8 times faster than for 2,6-dinitro-4-trifluoromethylanisole.I t should be noted that, in the case of 3, k-1 was calculated based on the assumed value k30H = 4.7 X lo7 M-' sec-I. Below it will be shown that it would not be unreasonable to assume a slightly higher value for k30H. As a consequence, k-1 for 3 in 70% Me2SO would also become larger, by the same relative amount as k30H
.'
Bernasconi, Terrier / Spiro Meisenheimer Contole.res
7464 The effect of changing the solvent from 70 to 80% MezSO on kl also appears “reasonable”, though a slightly greater increase might have been a n t i ~ i p a t e d ; ~ .for ’ a discussion of k - I , see below. Rates of Proton Transfer. H30+ and OH-. The high rate constant, k-3 = 2.86 X 1O’O M - ’ sec-I, for the protonation of 2 by H 3 0 + makes it evident that this reaction is diffusion controlled,16 just as the analogous reaction of 1 in aqueous solution.17 It is the first report of such a proton transfer rate in this solvent system; in view of D e l p u e ~ h ’ s ’recent ~ findings on proton transfers in pure MelSO, our result is not surprising. Although we could not determine k-3 for the reaction of 3 with H 3 0 + in the same solvent, there can be little doubt that it must be about the same as for 2. In our analysis, we assumed that this is also true in 80% Me2SO. A most interesting finding is that k30H for 2 in 70% Me2SO is about 100-fold lower than that for 1 in water. Since the increased viscosity can a t best explain a rate decrease by a factor of 3 to 4, two other possible interpretations come to mind: (1) ion pairing between O H - and (CH3)4N+; (2) intramolecular hydrogen bonding to the onitro group in XH.I6 I n view of the rather high dielectric constant (D F= 69.5 in 70% Me2S0, D F= 64.7 in 80% Me2S01*), ion pairing is not expected to be very significant; based on comparisons with known systems,20-21the ion association constant is expected to be smaller than 10, possibly very much smaller. Even with an association constant of 10, there would still be 20% free ions; even if only the free ions were reactive, this could still not account for more than a fivefold reduction in k 3 0 H . It is clear that intramolecular hydrogen bonding must be a n important (additional) factor. One would in fact expect such hydrogen bonding to become increasingly important when changing the solvent from water to 70% Me2SO. In a related system, weak intramolecular hydrogen bonding was invoked even in a 10% dioxane-90% water solution in order to explain a value of 2 x IO8 M-I sec-l for k3OH.l2 For 3, k30H could not be measured; in 70% MezSO, we have simply assumed k30H to be the same as that for 2. This implies that the strength of the intramolecular hydrogen bond is the same in both complexes. It is conceivable that the negative charge density on the o-nitro group of 3 is slightly different from the one on the two o-nitro groups of 2; this would probably affect the hydrogen bond strength. Let us assume that, in 3, the p-nitro group bears a substantially larger fraction of the charge than the o-nitro group, as suggested by the numerous observations that the p-nitro group is more effective in stabilizing a - c o m p l e ~ e sIf. ~ we further assume that, in 2, most of the negative charge resides on the nitro groups so that any one carries a larger fraction than does the o-nitro group in 3, the hydrogen bond in 3 would presumably be weaker than that in 2, and thus k 3 0 H for 3 should be assumed >4.2 X l o 7 M - ’ sec-I. As mentioned above, k-l would become larger too, thus increasing the difference in k-1 between 2 and 3 in the direction of that found in the reaction of methoxide ion with anisoles. On the other hand, the inverse assumption, viz.’, that it is 3 which has a stronger hydrogen bond, would bring k-1 for 3 closer to or even below that of 2 which would be difficult to rationalize. Based on these considerations, we tentatively conclude that any difference in the hydrogen bonding strength between 2 and 3, if significant a t all, is more likely to be in the direction 2 > 3. I n going from 70 to 80% Me2S0, an even stronger hydrogen bond is expected. W e have assumed that this lowers k j o H by another factor of 10; with this assumption, one obtains a “reasonable” k-l value as well as “reasonable” k3BI Journal of Ihe American Chemical Society
/
97:26
values (see below). The factor could, however, well be only 3 to 5; the alternative assumption that there is no further strengthening of the hydrogen bond in the less polar solvent would, however, lead to k-l and k3BI values which are larger in 80 than 70% Me2S0, a n unrealistic result. Rates of Proton Transfer. Buffers. The rate constants of the reactions X H B1- is XBH1 are summarized in Table V. The data for 2 in 70% MezSO a r e again the most reliable since they do not depend on any assumptions as to the value of k 3 0 H .The reaction from left to right is thermodynamically favored (ApK > 0) for all buffers, and thus no great dependence of k3B1 on ~ K Bis, expected.16 Indeed the k3BI values differ very little; they a r e about four to eight times lower than k30H which is comparable to other proton transfer reactions in aqueous s o l ~ t i o n . It~ ~is .nevertheless ~~ somewhat surprising that, even for BI = p-cyanophenolate ion, for which ApK is less than 2, k3BI is not significantly lower than those for the buffers with much larger ApK values. The possible significance of these findings with respect to the mechanism of deprotonation of intramolecularly hydrogen bonded species has been discussed elsewhere.lh The k3Bl values for 3 in 70% Me2SO a r e all slightly higher than for 2 despite smaller ApK values. This could be an artifact because the k3Bl’s depend on which value is assumed for k 3 0 H .However, lowering the k 3 B I ’ ~is only possible by assuming a lower k 3 0 H , implying a stronger hydrogen bond in 3 compared with 2, contrary to our earlier conclusions. A more satisfactory explanation of the higher k3BI values is therefore in terms of a reduced steric hindrance (one instead of two o-nitro groups) to the attack by B I . In 80% MezSO, the k3BI values obtained under the assumption that k30H is lowered tenfold compared with 70% Me2SO a r e about three to four times lower than that for 3 in 70% MelSO. This is consistent with stronger hydrogen bonding in the less aqueous solvent and was one of the criteria in assuming a tenfold decrease in k 3 0 H . Implications with Respect to the Mechanism of Base Catalysis in Nucleophilic Aromatic Substitution. The most widely accepted mechanism of base catalysis in nucleophilic aromatic substitutions by amines2’ is shown in Scheme I I .
+
+
Scheme I1
X
s
+
X
NHRR’
S‘ 4
5
~~~~~~~~
s 6
7
It was originally proposed by Bunnett;lX k3’ and k--3’ are defined by eq 1 and 2, respectively, whereas k4’ is defined byeq 17
k4’ = k 4 [ H + ]
+ kdoH + 2I k4Bd[BHi]
( 1 7)
i=
where kq and k4Bi refer to hydronium ion and general acid catalyzed leaving group expulsion, respectively, and k401’ to a nonassisted or solvent assisted pathway. I n basic solutions, the k 4 [ H + ] term is expected to be very small and thus is usually not included. The second-order rate constant for the over-all reaction
/ December 24, 1975
7465 of Scheme 11, derived by treating both 5 and 6 as steady states, is given by
In all discussions of this mechanism, it has been assumed that the equilibrium between 5 and 6 is rapidly established and that the k4’ step is rate limiting (SB-GA mechan i ~ m * ~In) . fact, assuming k-3’ >> k4’ leads to the following simplification of eq 18
by more than two orders of magnitude. On top of that comes the likely reduction of k3’ due to intramolecular hydrogen bonding and/or ion pairing. Thus in 60% dioxane, k-3’ > k-3‘. In fact, a rough guide of what to expect for k4’ can be obtained from the rate ( k = 42 sec-l 15) of methoxide ion expulsion from 8 in methanol. Based on the reactions, in CH,O
OCH3
with 8
According to this view, base catalysis is observable as long as k-1 is larger than or similar to K3’k4‘; when K3’k4’ >> k-1 we have kA = k l . If on the contrary one assumes k-3’ > k4‘. This would imply the SB-GA mechanism. However, in view of Jencks’ rule,35 this is unlikely.36 Experimental Section Materials.
N,N’-Dimethyl-N-(2,6-dinitro-4-trifluoromethyl-
pheny1)ethylenediamine hydrochloride and N,N’-dimethyl-N(2.4-dinitrophenyl)ethylenediamine hydrochloride (AH*+) were prepared by adding a solution of 5 g (40 mmol) of N,N’-dimethylethylenediamine monohydrochloride in 20 ml of ethanol (prepared and HCI) dropwise to in situ from N,N’-dimethylethylenediamine a solution of 5.4 g ( 2 0 mmol) of 4-trifluoromethyl-2,6-dinitrochlorobenzene (Pierce) or 4.05 g (20 mmol) of 2.4-dinitrochlorobenzene (Aldrich) in 40 ml of ethanol. The monohydrochloride of N,N’-dimethylethylenediamine rather than the free base was used in order to prevent nucleophilic attack on two aromatic substrates to form “dimers”, e g , N,N’-dimethyl-N,N’-bis(2,4-dinitropheny1)ethylenediamine. Nevertheless, small amounts of yellow precipitates were formed, presumably the dimers, which were filtered off. The filtrates were concentrated to about 20 ml which led to precip-
Bernasconi, Terrier
/
Spiro Meisenheimer Complexes
Sloan Foundation. One of us (F.T.) thanks the N A T O for a travel fellowship. W e also thank Professor J. F. Bunnett for criticism of the manuscript. References and Notes
calomel, saturated aqueous KCI
saturated KCI i n water--Me,SO (30-70 or 20-80)
\
1
Reference (SI
test solution in water--Me,SO, (30-70 or 20-80) ionic strength 0.5 .?I (acidic, basic or buffer solution)
H,(g,
1 a t m ) , Pt
The potential of the hydrogen electrode is measured relative to an internal reference in the solvent mixture S. The pH values so obtained and listed in the various tables are relative to the standard state in each solvent H20-Me2SO-0.5 M NMed+CI-. Details of all the experiments and results, including the determination of K s . will be reported in a separate paper. By means of the pH scales so determined, we could standardize a glass electrode, the response of which was perfectly linear with a slope close to 58 m V per pH unit in the pH ranges studied (8.6413.49 in 70% Me2SO; 1 1.91 -1 3.56 in 80% Me2SO). The pH measurements were made with a Corning Model l I O pH meter.
Acknowledgment. This work was supported by grants from the National Science Foundation and the Alfred P.
Journal of the American Chemical Society
(1) Part XIIi: C. F. Eernasconi and R. G. Eergstrom, J. Am. Chem. Soc.,96, 2397 (1974). (2) (a) Alfred P. Sloan Fellow, 1971-1973; (b) present address: ENSCP, 11, rue Pierre et Marie Curie, Paris 5s. (3) C. F. Bernasconi and C. L. Gehriger, J. Am. Chem. Suc., 96, 1092 (1974). (4) (a) M. Eigen and L. DeMaeyer, Tech. Chem. (N.Y.), 6, Part 2, 63 (1974); (b) G. G. Hammes, ibid., 6, 147 (1974). (5) E. Chance, Tech. Chem. (N.Y.). 6, Part 2, 5 (1974). (6) We use the symbol E1 for the buffer to distinguish from the other general bases, Bi ( i = 2, 3). present, such as AH or X-. (7) (a) J.-C. Halle. R. Gaboriaud. and R. Schaal, Bull. SOC. Chim. Fr., 2047 (1970); (b) J. F. Bunnett and G. T. Davis, J. Am. Chem. Soc., 80, 4337 (1958). (8)The only exception is for benzimidazole (Table 11). We note, however, that there exists a similar scatter in the initial slopes (footnote / o f Table V). suggesting that there must be a different reason for the scatter, possibly imperfect pH control. (9) For recent reviews, see (a) M. R. Crampton, Adv. Phys. Org. Chem., 3, 211 (1969); (b) M. J. Strauss, Chem. Rev., 70, 667 (1970). (10) (a) F. Terrier and F. Millot, Bull. SOC.Chim. Fr., 1743 (1970); (b) ibid., 1823 (1974). (1 1) V. Gold and C. H. Rochester, J. Chem. Soc., 1687 (1964). (12) Estimated by extrapolating from data in 80% Me2SO-20% MeOH using Figure 7 of Terrier et aI.l3 (13) F. Terrier, C. Dearing, and R. Schaai, Roc. 21st Meet. SOC. Chim. Phys., 137 (1973). (14) J. H. Fendier, J. Am. Chem. Soc.,88, 1237 (1966). (15) C. F. Eernasconi, J. Am. Chem. SOC.,90, 4982 (1968). (16) M. Eigen. Angew. Chem., lnt. Ed. Engl., 3, l(1964). (17) The somewhat lower value in 70% Me2SO is consistent with the approximately fourfold greater viscosity. " (18) G. J. Janz and R. P. T. Tomkins. "Nonaqueous Electrolyte Handbook", Voi. 1, Academic Press, New York, N.Y., 1972. (19) J. J. Delpuech in "Chemical and Biological Applications of Relaxation Spectrometry". E. Wyn-Jones, Ed., D. Reidel, Dordrecht-Holland, 1975, p 365. (20) M. Szwarc, "Carbanions, Living Polymers and Electron Transfer Processes", Wiley-Interscience, New York, N.Y., 1968, p 212. (21) See, e.g., E. A. Moelwyn-Hughes. "The Chemical Statics and Kinetics of Solutions". Academic Press, New York. N.Y., 1971, p 66. (22) C. F. Eernasconi, J. Phys. Chem., 75, 3636 (1971). (23) (a) F. Terrier, A. P. Chatrousse, and R. Schaai. J. Org. Chem., 37, 3010 (1972); (b) F. Terrier, F. Millot. and R. Schaal, J. Chem. Soc., Perkin Trans2, 1192(1972). (24) J. H. Fendler. E. J. Fendier, and C. F. Griffin, J. Org. Chem., 34, 689 (1969). (25) M.-L. Ahrens and G. Maass, Angew Chem., lnt. Ed. Engi., 7, 818 (1968). (26) C. F. Bernasconi and F. Terrieiin "Chemical and Biological Applications of Relaxation Spectrometry", E. Wyn-Jones. Ed., D.Reidel, DordrechtHolland, 1975, p 379. (27) For a recent review, see C. F. Eernasconi, MTP Int. Rev. Sci.: Org. Chem., Ser. One, 3, 33 (1973). (28) (a) See ref 27 in J. F. Bunnett and G. T. Davis, J. Am. Chem. Soc.,82, 665 (1960); (b) J. F. Eunnett and R. H. Garst. hid., 87, 3879 (1965). (29) A more familiar form of eq 19 (in basic solution) is
(30) J. F. Bunnett and J. J. Randall, J. Am. Chem. Soc.,80, 6020 (1958). (31) H. S. Harned and L. D. Faiion, J. Am. Chem. Soc.,61, 2374 (1939). (32) J. F. Eunnett and R . H. Garst, J. Org. Chem., 33, 2320 (1968). (33) J. F. Bunnett, T. Kato, and N. S. Nudelman, J. Org. Chem., 34, 785 (1969). (34) (a) M. R. Crampton, J. Chem. SOC.,Perkin Trans. 2, 2157 (1973); (b) M. R . Crampton and M. J. Willison, ibid., 1681 (1974). (35) W. P. Jencks. J. Am. Chem. SOC.,94, 4731 (1972). (36) For further elaboration, see C. F. Eernasconi, R. H. deRoss1. and P. Schmid, to be published.
/ 97.26 / December 24, 1975
