2746
Journal of the American Chemical Society
/
102:8
/ April 9, 1980
Role of Through Space 2p-3d Overlap in the Alkylation of ( a - N , N -Dimethylaminoalky1)diphenylphosphines and in the Alkaline Decomposition of Related Quaternary Phosphonium Salts William E. McEwen,* Joanne H. Smith, and Edward J. Woo Contribution from the Department of Chemistry, Unioersity of Massachusetts, Amherst, Massachusetts 01003. Receiaed Nooember 19, 1979
Abstract: A series of (o-N,N-dimethylaminoalkyl)diphenylphosphines has been prepared and subjected to reaction with benzyl chloride in benzene-methanol (60:40 v/v) a t 3 1 .O f 0.1 O C . Each of the quaternization reactions was found to follow the second-order rate law, and the data indicated the operation of a modest degree of through space 2p-3d overlap between the amino nitrogen and the phosphorus atom in the transition state. A series of quaternary phosphonium bromides containing an w-N,N-dimethylaminoalkylgroup bonded to phosphorus was prepared and subjected to hydroxide-induced decomposition reactions in MqSO at 22.0 f 0.1 O C . Each reaction was found to follow the third-order rate law, and the data indicated the operation of a pronounced through space 2p-3d overlap effect. Finally, a series of quaternary phosphonium iodides containing an o-methoxyalkyl group bonded to phosphorus was prepared and subjected to hydroxide-induced decomposition reactions in dioxane-water ( I : I ) at 45.0 & 0. I OC. Each reaction was found to follow the third-order rate law, and the relative velocities of reaction were found to be influenced by the inductive, electron-withdrawing effect of the methoxy group bonded to a saturated carbon atom of sufficient magnitude to mask any possible 2p-3d overlap effect.
Introduction Kinetics data for the s N 2 reactions of various triarylphosphines with benzyl chloride, benzyl bromide, and n-butyl chloride, and of aryldiethylphosphines with ethyl iodide, have been presented in previous p ~ b l i c a t i o n s . l Four - ~ particularly important effects were observed. (1) The presence of an omethoxy substituent on an aryl group of the phosphine causes a significant increase in the rate of the reaction. (2) The ratio of the rates of reaction of a given triarylphosphine with benzyl chloride and with n-butyl chloride is about 20, probably the smallest such ratio ever reported for S Nreactions ~ of these alkyl chlorides. (3) Rate and activation-parameter profiles for the reactions of the isomeric anisyldialkylphosphines and anisyldialkylamines, respectively, with alkyl halides are distinctly different. (4) Diphenyl(2,6-dimethoxyphenyl)phosphine undergoes the quaternization reaction with alkyl halides faster than any other phosphine we have used, including tris(o-anisy1)phosphine and bis(o-methoxypheny1)phenylphosphine.A rationalization of these observations has been presented based partly on the concept of through-space overlap of a pair of 2p electrons of the oxygen atom of a 2-methoxyphenyl group with an empty 3d orbital (or hybrid orbital) of phosphorus in an early transition state, this phenomenon being modified by the effects of ortho substituents on CPC bond angles and by possible double overlap effects. It has also been ~ u g g e s t e d l that, - ~ if a through space 2p-3d overlap effect exists in the transition state of an sN2 reaction, it will also be apparent in the phosphonium cation which is the product of the reaction. Three lines of support for this concept have been offered. ( 1 ) An X-ray diffraction study of benzyl(2-methoxyphenyl)diphenylphosphonium bromide has revealed that the P - 0 distance is substantially shorter than the sum of the van der Waals radii of phosphorus and oxygen. Furthermore, the bond angles indicate that the o-methoxyphenyl group is actually leaning toward the phosphorus in order to facilitate a P-0 bonding interaction, and energy minimization calculations, in which the total steric energy is made up primarily of bond stretching energies and van der Waals nonbonded interactions, also indicate that a weak P-0 bonding interaction exists. (2) For reasons cited in the previous papers,'-4 the chemical shift of the protons of the methylene group directly bonded to phosphorus in the phosphonium salt 0002-7863/80/ 1502-2746$01 .OO/O
represents the best probe of the overlap effect in the N M R spectrum of each compound. An upfield shift of the methylene hydrogens is expected when the electron density at phosphorus is increased owing to the overlap effect, and this is observed. (3) The rates of alkaline cleavage of a series of benzyltriarylphosphonium chlorides in 50% v/v aqueous dioxane at 10.1 O C have been determined.6 The salts containing o-methoxy groups have been found to undergo reaction much more slowly than those containing p-methoxy groups. For example, benzylbis(o-methoxypheny1)phenylphosphonium chloride reacts but 2.6 X times as fast as benzylbis(p-methoxypheny1)phenylphosphonium chloride. Benzyl(2,6-dimethoxyphenyl)diphenylphosphonium chloride reacts about ten times slower than the bis(o-methoxyphenyl) compound. These are the results anticipated based on the operation of the through-space 2p-3d overlap effect of the ortho-substituted compounds. It has also been found4 that, in the attempted reaction of diphenyl(methoxymethy1)phosphine with benzyl chloride, the inductive, electron-withdrawing effect of a methoxy group bonded to a saturated carbon atom is so large that the rate of reaction with benzyl chloride in benzene-methanol a t 3 1 O C is essentially zero. I n the reaction of diphenyl(4-methoxybuty1)phosphine with benzyl chloride, the inductive effect is still being felt, even though four methylene groups intervene between the phosphorus atom and the methoxy group, as evidenced by the fact that the rate is slightly lower than that of the reaction of diphenyl-n-butylphosphinewith benzyl chloride. I n spite of what must be large rate-depressing inductive effects of the methoxy group in the reactions of diphenyl(2methoxyethy1)phosphine and diphenyl(3-methoxypropy1)phosphine with benzyl chloride, these reactions are faster than those of diphenylethylphosphine and diphenyl-n-propylphosphine, respectively. Thus, it was concluded4 that the 2p-3d overlap must be significant in the cases of the 2-methoxyethyl and 3-methoxypropyl compounds, inasmuch as the overlap effects are still apparent even though masked by the counterbalancing inductive effects. Since these results have important implications with respect to hydrolysis and exchange reactions of biologically important phosphate esters, in which alkoxy1 groups of carbohydrate moieties are almost always in close proximity to the phosphorus atom of the phosphate group, we decided to expand the study to include the effects of methoxyalkyl groups on the rates of alkaline cleavage of quaternary
0 1980 American Chemical Society
McEwen. Smith, Woo
/ Alkylation of (w-N,N-Dimethylaminoalkj~1)dipkenylphospkine.s
2747
Reactions of (w-,~,;.,Y-Dimethylaminoalkyl)- Table 11. Rate Data for the Decomposition of Phosphonium Hydroxides at 22.0f 0.1 OC in Me,SO diphenylphosphines with Benzyl Chloride in Benzene-Methanol (3:2)at 21.0f 0.1 "C Table I. Rate Data for
phosphonium bromide phosphine
diphenyl[2,6-dimetho~yphenyl)-~
tris(o-anisql)-l bis(o-anisy1)phenyl-'
diphenyl(o-anisy1)-l diphenyl~nethyl-~ diphenyl( 2-metho~yethyl)-~
diphenyl(3-metho~ypropyl)-~ di~henylethyl-~ (N,N-dimethylaminomethy1)diphenyl(6-N,N-dimethylaminobutyl)diphenyl-
diphenyl-n-butyl-4 diphenyl-n-pr~pyl-~ (@-N,N-dimethylaminoethy1)diphenyl-
(y-N,N-dimethylaminopropy1)diphenyltriphenyl-' diphenyl(methoxymethyl)-4
539 f 32 195 f 4 I46 f 3 53.6f 0.7 35.5 f 0.3 33.8f 0.3 3 1.2f 0.2 27.1 f 0.1 26.6f 0.2 26.5 f 0.2 26.0 f 0.1 25.9 f 0.1 18.9 f 0.2 13.7f.2 7.22f 0.13 O.OOb
Average deviation based on four to ten experimental results. Too slow to measure under conditions cited. a
phosphonium salts, and also to examine the effects of w-N,N-dimethylaminoalkylgroups in both alkylation of phosphines and the alkaline cleavage of phosphonium salts.
benzyltriphenql- a (y-N,N-dimethylaminopropy 1)diphenylbenzyl(P-N,N-dimethylaminoethy 1)diphenylbenzyl(6-N,N-dimethylbutjl)diphenylbenzyl(N,N-dimethylaminoethy1)diphenylbenzyl-
2310 f 1 31.7 f 0.3 16.2f 0.2 5.7 f 0.7 5.1 f 0.5
a The decomposition reactions of simple alkyldiphenylbenzylphosphonium hydroxides (alkyl = methyl, ethyl, n-propyl, n-butyl) were too fast to be measured under these conditions.
Table 111. Rate Data for the Decomposition of Phosphonium Hydroxides a t 45.0 f 0. I "C in Dioxane-Water ( 1 : 1)
phosphonium iodide
(methoxymethy1)diphenylbenzyl(P-methoxyethy1)diphenylbenzyl-
methyldiphenylbenzyl(y-methoxypropyl)diphenylbenzylethyldiphenylbenzyl(6-methoxybuty1)diphenylbenzyln-propy ldiphenyl benzyl-
n-butvldiDhenvlbenzvl-
1750 f 80 94.3f 12.3 16.7 f 0.3 4.19f 0.10 1 .I6f 0.06 1.64 f 0.02 1.38 f 0.10 0.917 f 0.050
decreases the nucleophilicity of the phosphine and causes a Results decrease in the rate of the S y 2 reaction with benzyl chloride, but it increases the electrophilic reactivity of the phosphorus (N,N-Dimethylaminomethy1)diphenylphosphine and the atom in the phosphonium salt and, by causing an increase in homologous P-N,N-dimethylaminoethyl-, y-N,N-dimethylamino-n-propyl-, and 6-N,N-dimethylamino-n-butylphos-the concentration of the intermediate hydroxyphosphorane,8-19 brings about an overall increase in the rate of alkaline cleavage. phines were prepared and subjected to reaction with benzyl There is no clear evidence of a 2p-3d overlap effect in either chloride in benzene-methanol (60:40 v/v) at 3 1.O f 0.1 "C. reaction. All of the quaternization reactions were found to follow the second-order rate law, and the results are summarized in Table It is also apparent from the data presented in Table 111 that there is no major influence on rates of alkaline cleavage of the I, together with a few selected results from previous studies for other w-methoxyalkylphosphonium salts caused by possible purposes of comparison. 2p-3d overlap effects. This can best be seen by means of a Four new quaternary phosphonium bromides containing an comparison of the rate ratios for each w-methoxyalkylphosw-dimethylaminoalkyl group bonded to phosphorus were phonium hydroxide decomposition to the corresponding simple prepared and subjected to hydroxide-induced decomposition alkylphosphonium hydroxide decomposition. For example, the reactions in Me2SO at 22.0 f 0.1 O C . For purposes of comratio of the third-order rate constants for the (methoxyparison, benzyltriphenylphosphonium bromide was subjected to the same reaction conditions. All of the reactions were found methy1)diphenyIbenzylphosphonium hydroxide and methylto follow the third-order rate law, and the results are summadiphenylbenzyl phosphonium hydroxide decomposition reacrized in Table 11. tions is 1750/16.7 = 105. The corresponding ratios for the Four new quaternary phosphonium iodides containing an remaining pairs of reactions are 0-methoxyethyllethyl = 54, w-methoxyalkpl group bonded to phosphorus were prepared y-methoxypropyl/n-propyl = 3, and 6-methoxybutyl/n-butyl and subjected to hydroxide-induced decomposition reactions = 1.8. These results would seem to reflect mainly a normal dampening of the inductive, electron-withdrawal effect of the i n dioxane-water ( 1 : l ) a t 45.0 f 0.1 "C. For purposes of comparison, the corresponding methyl, ethyl, n-propyl, and methoxy group bonded to a saturated carbon atom as the n-butyl salts were also subjected to the same reaction condinumber of methylene groups from the phosphorus atom is increased. At the very least, any possible 2p-3d overlap effect tions. All of the reactions were found to follow the third-order is being masked quite effectively by the inductive effect.*O rate law, and the results are summarized in Table 111. The apparent effects of the presence of w-N,N-dimethylDiscussion amino groups on the rates of alkylation reactions, shown in Table I , are not impressive. However, the same type of arguIn general, as found in previous ~ t u d i e sthere , ~ is an inverse ment as used in the corresponding (w-methoxyalky1)phosphine relationship between the rate of alkylation of a given phosphine and the rate of decomposition of the corresponding quaternary reactions4 can be invoked for the occurrence of at least a weak phosphonium hydroxide. For example, as shown in Table I, 2p-3d overlap effect. The inductive, electron-withdrawing effect of a dimethylamino group bonded to a saturated carbon diphenyl(methoxymethy1)phosphine does not undergo reaction with benzyl chloride at a measurable rate in benzene-methanol atom is not as large as that of a methoxy group,j but it is nev(3:2) at 31 .O f 0.1 "C. However, as shown i n Table 111, (meertheless appreciable.*' Nevertheless, each (w-N,N-dithoxymethy1)diphenylbenzylphosphonium iodide undergoes methylaminoalky1)phosphine undergoes reaction with benzyl the alkaline decomposition reaction in dioxane-water ( 1 : I ) a t chloride at about the same rate as the corresponding simple 45.0 f 0.1 O C a t a faster rate than any of the other phosphoalkylphosphine. Specifically, the ratio of the rates of reaction nium iodides listed. Clearly, it is the inductive, electronof ( N ,N - d i me t hyla mi nome t h y I ) d i p hen y 1phosphine and withdrawing effect of a methoxyl group bonded to a saturated methyldiphenylphosphine with benzyl chloride is 26.6/35.5 carbon atom7 which is responsible for both results. This effect = 0.75. The corresponding ratios for the remaining pairs of
2748
Journal of the American Chemical Society
Table IV. N M R Absorption Data Taken in CDC13 or CD30D Solution for the Methylene Hydrogens of Phosphonium Bromides
ohomhonium cation
6. DDm ICH,)
benzytriphenyP
5.32
o-anisylbenzyldiphenyl-a
5.10 4.82 4.67
bis(o-anisyl)benzyldiphenyl-" tris(o-anisyl)benzyldiphenyl-a (N,N-dimethylaminomethyl)benzyldiphenyl-b (P-NJ-dimethy laminoethyl)benzyldiphenyl-b (y-N,N-dimethylaminopropyl)benzyldiphenyl-b (6-N,N-dimethylaminobutyl) benzyldiphenyLb
4.01 -4.22c 4. 1O-4.4Oc
4.27-4.4OC 4.06-4.45'
a CDC13 solution. CD3OD solution. The presence of two 2H peaks, each with evidence of splitting, prohibited definitiveassignment
'of J values.
reactions are P-N,N-dimethylaminoethyl/ethyl= 0.70, y-N,N-dimethylaminopropyl/n-propyl = 0.53, and 6-N,N-dimethylaminobutyl/n-butyl = 1.02, Thus, in spite of what must be substantial rate-depressing inductive effects of the dimethylamino group, the compensating through space 2p-3d overlap effects are causing the ratios cited above to be close to unity. The most convincing evidence for through space 2p-3d overlap involving the dimethylamino group as the donor is to be found by consideration of the rates of decomposition of phosphonium hydroxides containing the w-N,N-dimethylaminoalkyl group. Whereas the simple alkyldiphenylbenzylphosphonium hydroxides (alkyl = methyl, ethyl, n-propyl, and n-butyl) undergo decomposition i n Me2SO a t 22.0 f 0.1 'C at too rapid a rate to permit convenient measurement,22 the quaternary phosphonium hydroxides containing a n w-N,N-dimethylaminoalkyl group react at rates several orders of magnitude slower (Table 11). This observation can be explained in a satisfactory manner by application of HSAB theory.23 Tetrahedral phosphorus, with its high degree of positive charge and its empty d orbitals, resembles a proton in its reactivity. Thus, through space 2p-3d overlap is highly effective with a basic group as the donor; i.e., a dimethylamino group engages in more effective overlap than a methoxy group. The same would not apply to the S k 2 reactions of the phosphines, inasmuch as the transition state for this reaction is an early one,? 4.24 and the degree of positive charge on the phosphorus in the transition state is very small. The data presented previously4 and in Table I indicate that there is relatively little difference in the ability of nitrogen in the dimethylamino group and of oxygen in the methoxy group to act as the donor in the through space 2p-3d overlap effect as applied to the quaternization reactions. It is reasonable to believe that steric effects should play some role in determining the relative rates of the quaternization reactions of the (w-N,N-dimethy1aminoalkyl)phosphines as against those of the analogous (w-methoxyalky1)phosphines. It is obvious that the dimethylamino group is larger than the methoxy group, but there seems to be no direct comparison of the steric requirements of these tw'o substituent groups in the literature. However, an indirect comparison can be made. Taftz5 has listed the increasing order of steric hindrance of some common substituents to be OMe < F < Br Me < t-Bu, while similar steric effects for the MelN and t-Bu groups have been reported by Elie126on the basis of conformational studies of substituted cyclohexanes. Thus, in a comparison of the rate of reaction of (P-methoxyethy1)diphenylphosphinewith benzyl chloride as against that of (P-N,N-dimethylaminoethy1)diphenylphosphine, for example, two mutually antagonistic factors would have to be taken into consideration in addition to 2p-3d overlap effects. The reaction of the (P-ethoxyethy1)phosphine should be faster than that of the (P-N,N-dimethylaminoethy1)phosphineon the basis of steric
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102:8
/ April
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considerations, but, as mentioned p r e v i ~ u s l y , slower ~ . ~ ~ on the basis of the operation of the inductive effect. Thus, the effect that the P-methoxyethyl compound is somewhat less than twice as reactive as the &N,N-dimethyIaminoethyl compound, while not predictable, is also not surprising. The small differences in reactivity between the quaternization reactions of the y-methoxypropyl- and y-N,N-dimethylaminopropylphosphines and between the reactions of the 6-methoxybutyl- and 6-N,N-dimethylaminobutylphosphines, respectively, can also be rationalized in the same manner. The only major difference in reactivity between pairs of analogous phosphines involves the methoxymethyl- and N,N-dimethylaminomethylphosphines. Here, as mentioned previously, the very strong inductive electron-withdrawing effect of the methoxy group bonded to a saturated carbon, and removed from the phosphorus atom by but one methylene group, is the dominant factor in controlling the relative lack of reactivity of the methoxymethylphosphine. Examination of models indicates that the degree of steric interaction between the methyl and phenyl groups resulting from a binding interaction between the basic nitrogen and the positive phosphorus atoms in the phosphonium cations increases in the order M ~ ~ N ( C H ~ ) ~ P +
- -, (4) W.'E. McEwen, A. B. Janes, J. W. Knapczyk. V. L. Kyllingstad,W. I. Shiau. S. Shore, and J. H. Smith, J. Am. Chem. Soc., 100, 7304 (1978). (5) J. S. Wood, R. J. Wikholm, and W. E. McEwen, Phosphorus Sulfur, 3 , 163 (1977). (6) G. L. Keldsen and W. E. McEwen, J. Am. Chem. Soc., 100, 7312 (1978). (7) (a) The CT value for a methoxy group is +0.26.7b (b) A. J. Gordon and R. A. Ford, "The Chemist's Companion", Wiley, New York, 1972, p 153. (8) M. Zanger, C. A. Vander Werf, and W. E. McEwen, J. Am. Chem. Soc.,81, 3806 (1959). (9) W. E. McEwen, K. F. Kumli. A. Blade-Font, M. Zanger, and C. A. Vander Werf, J. Am. Chem. SOC.,86. 2378 (1964). (10) W. E. McEwen, G. Axelrcd, M. anger. and C. A. Vander Werf, J. Am. Chem. SOC.,87, 3948 (1965). (11) J. R. Corfield and S.Trippett, Chem. Commun., 1267 (1970). (12) D. W. Allen, J. Chem. SOC.6, 1490 (1970) (13) D. W. Allen, B. G. Hutley, and M. T. Mellor, J. Chem. SOC., Perkin Trans. 2, 63 (1972). (14) D. W. Allen and B. G. Hutley. J. Chem. SOC.,Perkin Trans. 2, 67 (1972). (15) D. W. Allen, 8 . G. Hutley, and M. T. J. Mellor, J. Chem. SOC.,Perkin Trans. 2, 1690 (1974). (16) F. Y. Khalil and G. Aksnes, Phosphorus Sulfur, 3, 27 (1977). (17) G. Aksnes. F. Y. Khalil, and P. I. Majewski, Phosphorus Sulfur, 3 , 157 (1977). (18) H. J. Cristau, H. Christol, and M. Soleiman. Phosphorus Sulfur, 4 , 287 (1978). (19) B. Siegel. J. Am. Chem. SOC.,101, 2265 (1979). (20) We could find no evidence for a competing elimination reaction in the decomposition of @4hoxyethyl)diphenylbenzylphosphonium hydroxide. The same observation has been made by Cristau, Christol, and Soleiman.18 (21) The (TI value for a dimethylamino group is +0.10 (ref 7b, p 153). (22) Khalil and Aksnes16 have discussed in depth the huge rate acceleration found in the decomposition of quaternary phosphonium hydroxides when Me2S0 is used as the solvent. (23) J. 0. Edwards and R. G. Pearson, J. Am. Chem. Soc.,84, 16 (1962). (24) T. Thorstenson and J. Songstad, Acta Chem. Scand., Ser. A, 30, 724 (1976). (25) R. W. Taft, Jr., in "Steric Effects in Organic Chemistry", M. S.Newman, Ed., Wiley, New York, 1956, pp 556-675. (26) E. L. Eliel, Angew. Chem., lnt. Ed. Engl., 4, 761 (1965). (27) A. M. Aguiar, J. Beisler. and A. Mills J. Org. Chem., 27, 1001(1962). A more convenient preparation has recently been published: P. W. Clark, Org. Prep. Proced. lnt., 11, 103 (1979). (28) H. Bohme, Chem. Ber., 1305 (1960). (29) C. R. Ganellin, J. Chem. SOC.,2220 (1967). (30) Commercially available. (31) K. B. Wiberg, "Laboratory Technique in Organic Chemistry", McGraw-Hill, New York, 1960, pp 245-246.
