J . Am. Chem. SOC.1980,102, 5329-5336
5329
Nucleophilic Addition to Olefins. 4.' Structure-Reactivity Relationships in the Reactions of Amines with Substituted Benzylidene Meldrum's Acids. Evidence for Intramolecular Proton Transfer to Carbon Claude F. Bernasconi* and Simonetta Fornarini Contribution from the Thimann Laboratories of the University of California, Santa Cruz, California 95064. Received December 24, 1979
Abstract: The reactions of piperidine and morpholine with benzylidene Meldrum's acid (1-H) and its p-OMe and p-NMe2 derivatives (1-OMe, 1-NMe,) in water are characterized by a fast and a slow kinetic process. The fast reaction refers to the formation of a zwitterionic adduct (TAi) which is in rapid acid-base equilibrium with TA- (eq 1). The slow process leads, via an iminium ion, to the respective benzaldehyde and Meldrum's acid anion (eq 3) whereby protonation of TA- on carbon, to form TAo,is rate limiting. The effect of the substituents in the olefin on rate ( k , ) and equilibrium constants ( K , ) for adduct formation indicate that the transition state is located approximately halfway between reactants and products (a log k l / d log K I = 0.40-0.45). On the other hand, &, is extremely low (0.07-0.12), suggesting that C-N bond formation has made very little progress in the transition state. These data then suggest an imbalanced transition state for which two different and possibly complementary explanations are proposed. According to the first, rehybridization of the benzylic carbon (site of nucleophilic attack) is ahead of C-N bond formation. In the second it is assumed that some negative charge is localized on the benzylic carbon in the transition state but delocalized into the (COO),C(CH,), moiety in the product, as has been suggested for the nitroalkane anomaly. Protonation of TA- on carbon by morpholinium ion is retarded 1000-fold owing to a steric effect; carbon protonation by the hydronium ion occurs mainly by prior equilibrium protonation on nitrogen, to form TAi, followed by an intramolecular proton switch, TAi -+ TAD(eq 3), through an intermediate water mokcule.
As noted
benzylidene Meldrum's acid (1-H) is a very
actions in acetonitrile and in chloroform. Results General Features. Upon mixing of 1-H, 1-OMe, or l-Me2N with an excess of piperidine or morpholine in aqueous solution one typically observes three kinetic processes. The fastest, with , to reaction 1. Depending on the relaxation time T ~corresponds
1-H, X = H 1-OMe, X = OCH, 1-NMe,, X = N(CH,),
reactive electrophile and appears well suited for studying structure-reactivity relationships in the nucleophilic addition to olefins. In a previous paper3 we described the rather complex kinetic behavior of 1-H in aqueous solution which arises (a) from nucleophilic attack by water and hydroxide ion to form TOH-, (b) from protonation of TOH- on carbon to form TOHo,and (c) from cleavage of ToHointo benzaldehyde and the anion of Meldrum's acid ( M H ) .
TOHo
MH
In the present paper we discuss the kinetic behavior of benzylidene Meldrum's acid as well as that of the 4-methoxy (1-OMe) and 4-NJV-dimethylamino ( 1-NMe2) derivatives in the presence of piperidine and morpholine in the same solvent. Our work complements a recent study by Schuster et of the same re( I ) Part 3: Bernasconi, C. F.; Fox, J. p.; Fornarini, s. J . Am. Chem. SOC. 1980, 102, 2810. ( 2 ) Schuster, P.; Polansky, 0. E.; Wessely, F. Tetrahedron, Suppl. 8, Part I I 1966, 463. ( 3 ) Bernasconi, C . F.; Leonarduzzi, G. D. J . Am. Chem. Soc. 1980, 102, 1361. (4) Schreiber, B.; Martinek,
H.: Wolschann, P.; Schuster, P. J . A m . Chem.
SOC.1979, 101, 4708.
0002-7863/80/ 1502-5329$01.OO/O
1
TAT
'i' H-C-CI
I
NR,
;:.of3
+coo -
(1) CH3
TA-
the pH, either TA* or T A - is the major species formed. The spectrum of TA*,A,(, 263 nm, t 14600) and that of T A - ,A,(, 269 nm, c 15 800) derived from 1-H and piperidine are shown in Figure 1; the spectra (not shown) of the morpholine adducts of 1-H and of the piperidine and morpholine adducts of 1-OMe and 1-NMe2are all very similar to the ones shown in Figure 1 as well as to that of TOH- ,,A,( 263 nm, c 17 000) and of the Meldrum's 258 nm, t 21 400). acid anion (A,, In all cases we found that the reciprocal relaxation time obeys the equation T
~
=- kl[R2NH] ~
+ k lK," O+H +aH+
or a special form thereof; this is consistent with rapid proton transfer (K,*) and rate-limiting nucleophilic attack (kl). The second kinetic process can be attributed to the addition of water or hydroxide ion to form TOH-.Since this reaction for ( 5 ) Schuster, P.; Stephen, A,; Polansky, 0. E.; Wessely, F. Monatsh. Chem. 1968, 99, 1246.
0 1980 American Chemical Society
5330 J. Am. Chem. SOC.,Vol. 102, No. 16, 1980
Bernasconi and Fornarini 20
1
I
0.7
I
l5 i
7 15 6 63
5t
6 15
I
00
2
6
4
8
IO5 x Morpholine3 , M Figure 2.
X, nm Figure 1. Spectra of TA*and TA- derived from 1-H and piperidine. [Pip] =5 X M, [&HI,, = 4.65 X M, pH 9.74 for TA*,pH 12.79 for
T*-. 1-H has been described before3 it will only be discussed to the extent that it interferes with the amine reactions. The slowest kinetic process, with the relaxation time T ~refers , to the cleavage reaction 3 where ki and k_irefer to an intramo-
l i d 1
TAo
7,-'
for the reaction of 1-H with morpholine.
solution; they refer to protonation on carbon to form ToHoand acid-catalyzed breakdown of TOH- to the olefin. The third process is much slower than the T~ process and refers to hydrolysis of the substrate. Since these processes have already been thoroughly analyzed3 they will not be discussed further. All kinetic results reported were obtained under pseudo-firstorder conditions with the olefin as the minor component; all measurements were in water at 25 OC and at a constant ionic strength of 0.5 M, maintained with KCl. Benzylidene Meldrum's Acid (1-H) Adduct Formation. Solutions of 1-H at pH 36 were mixed with amine solutions and the kinetics was followed in the stopped-flow apparatus by monitoring either the decrease in absorbance at 320 nm (1-H) or the increase in absorbance at 260 nm (TA*and/or TA-). With morpholine T ~ - ' was determined at pH 8.82, where morpholine acts as its own buffer, and at pH 7.15, 6.63, and 6.15 in cacodylate buffers. The results are summarized in Table Sl.' Plots of T ~ - Ivs. morpholine concentration at pH 7.15, 6.63, and 6.15 are shown in Figure 2. Points determined at different pH fall on the same straight line and thus are consistent with the equation TI-'
Mlecular proton switch, most likely with a water molecule as an intermediary (see Discussion), while k3p and k-3p are pseudofirst-order rate coefficients for intermolecular proton transfer, defined as k3p =
+
+
k3pHaH+ k3pW k3pAH[R2NH2f]
(4)
k-3p = k-3pW+ k - 3 p o H a ~+~ -k-3pA[R2NH]
(5)
with kjpH,k,,", and kjpAHbeing the rate constants for protonation of TA- on carbon by the hydronium ion, water, and the ammonium ion, respectively, and k-3pW,k_3p0H,and k-3pAbeing the rate constants for deprotonation of TAoby water, hydroxide ion, and the amine, respectively. This process was observed with all three olefins and was measurable by conventional spectrophotometric methods; it was investigated in detail for the morpholine/l-H pair only. We also conducted experiments in which the equilibrium of eq 1 was approached from the product side, by first generating TA* and/or TA- in basic solution, followed by mixing with an acidic solution (pH-jump experiments). In the course of performing these experiments we observed not only the relaxation time associated with reaction 1 ( T ~ but ) three additional kinetic processes. Two of these are faster than the T~ process and are due to reactions of TOH- which is cogenerated along with TA* and TA- in basic
= k,[RzNH]
+ k-1
(6)
which is a special case of eq 2 where aH+>> Kaf. From the slope we obtain k l = 2.04 f 0.2 X io5 M-I s-I and from the intercept k-l = 2.0 f 0.1 s-l. The data at pH 8.82 yield k l = 1.50 f 0.2 X IO5 M-I SKI,We shall use the average, 1.75 X IO5 M-I s-I , in our subsequent discussion. Further evidence that the intercept in Figure 2 corresponds to k-l (eq 6), implying aH+>> Kaf, comes from pH-jump experiments which were conducted in the following way. The olefin was first mixed with enough morpholine buffer at pH 9.05 to convert it virtually quantitatively into a mixture of TAf and TA-.8 This solution was then mixed with an acidic buffer in the stopped-flow apparatus. Under these conditions the reaction corresponds essentially to an irreversible breakdown of TA*and/or TA- according to TA-
& TA* K.*
k-i -*
1 + RzNH
(7)
with
(6) Acidic solutions were required to prevent conversion of the olefin into TOH-.
(7) See paragraph at end of paper regarding supplementary material. (8) Some TOH-is also formed.
J . Am. Chem. SOC.,Vol. 102, No. 16, 1980 5331
Reactions of Amines with Benzylidene Meldrum's Acids Table I. Reactions of Benzylidene Meldrum's Acid and of 4MethoxybenzylideneMeldrum's Acid with Morpholine and Piperidine. pH-Jump Experiments
~~~
4.01 3.71 3.39 3.07 3.07 2.76 2.76
formated formated formated HC1 HC1 HC1
HCl
Morpholine + 1-Hn 1.70 x 10" 8.50 X IO-' 4.08 X 1.95 x 2.5 x 10-3 4.89 x 5.0 x 1 0 - 3 4.80 x 10-3 9.60 X
Piperidine + 1-He 2.0 x 5.92 X 2.0 x 10-4 5.92 x 2.0 x 10-4 5.92 x R 5.0 x 10-4 1.48 x R 10-3 2.96 X R 2 x 10-3 5.92 x I: 3 x 10-3 8.90 x R 3.9 x 10-3 1.15 x 7.03 cacodylateg 9.8 X 4.06 x R 2 x io-' 8.34 x R 4 X 10.' 1.67 X g 8 X 10" 3.33 X g lo-] 4.17 X
6.88 cacodylatd f f
2.84 HCl 1.87 HCl 1.89 HCl
Morpholine + 5 x 10-3 5 x 10-3 1.2 x 10-2
10-7
2.02 1.97 1.97 lo-a 2.01 10-9 1.96 10-9 2.04 10-lo 1.98
10-9 10-9 10-8
lo-' 10-8
10-8 10-7 10-7
1-OMeh 5.74 x 10-9 6.14 x 1 0 - 1 0 1.55 x 10-9
1.60 X 1.69 X 1.70 X 1.61 X 1.74 X 1.61 X 1.49 X 1.62 X 7.80 x 6.47 x 5.45 x 3.96 x 3.54 x
lo-'
10.' 10.' lo-' lo-' lo-' lo-' lo-' 104
10-3 10-3 10-3 10-3
9.87 9.77 9.80
Piperidine t 1-OMeh 5 x 10-3 1.44 x 1 0 - 1 1 7.74 x 2.86 HCI 1.88 HCl 5 x 10-3 1.51 x 1 0 - 1 2 7.78 X 1.88 HCl 3.02 X 7.59 x 10-2 [Substrate], = 2.5-4.2 X M, monitored at 320 and/or 260 nm. Total amine concentration. Free amine concentra1.3 X lo-*, and tion. Total buffer concentration 9.8 X 2.05 x Mat p H 4.01, 3.71, and 3.39, respectively. e [Sub strate] = 1.1-2.3 X M, monitored at 240 nm. Total buffer concentration 3.2 X 6.4 X lo-', and 1.28 X lo-' M in first, second, and third run,respectively. g Total buffer concentration 6.4 X 10" M. [ Substrate] ,, = 2-4 X 10'' M, monitored at 370 nm. The results are summarized in Table I. They show again that T ~ is - pH ~ independent because aH+>> Kaf and thus T , - I = kl with k-, = 1.98 f 0.05 s-I, in agreement with the data in cacodylate buffers. With piperidine T ~ - I was measured at pH 8.40 in an N methylmorpholine buffer, at piperidine concentrations ranging from to 2 X lo4 M. The results are summarized in Table S2;7 T!-' obeys eq 6 with k l = 2.70 f 0.20 X lo5 M-I s-l while k-, is indistinguishable from zero. A value for k l was obtained from pH-jump experiments which were conducted in a similar way as in the morpholine reaction and the results of which are included in Table I. At pH 6.88 and a free piperidine concentration 5 1.15 X lo-' M T ~ is- seen ~ to be independent of amine concentration ( k , [ R 2 N H ]
