|
1. |
Solvent effects on Diels-Alder reactions. The use of aqueousmixtures of fluorinated alcohols and the study of reactions ofacrylonitrile |
|
Journal of the Chemical Society, Perkin Transactions 2,
Volume 1,
Issue 4,
1997,
Page 653-660
Carlos Cativiela,
Preview
|
|
摘要:
Solvent eVects on Diels–Alder reactions. The use of aqueous mixtures of fluorinated alcohols and the study of reactions of acrylonitrile Carlos Cativiela Jose I. García,*,a J. Gil,a Rosa M. Martínez,a Jose A. Mayoral,*,a Luis Salvatella,a Jose S. Urieta,a A. M. Mainar a and about the influence of the different solvation mechanisms on the results of Diels–Alder reactions have been carried out with carbonylic dienophiles.2 Even for such a restricted family of dienophiles it has been shown that solvent effects may be dependent on the nature of the dienophile. Therefore it is interesting to consider dienophiles other than carbonyl derivatives in order to get a more general insight into solvent effects on this kind of reaction. Thus in this work we also present the results obtained in the study of solvent effects on the Diels–Alder reactions of a different type of dienophile namely acrylonitrile (13) by means of a multiparametric approach.The responses chosen are the kinetic rate constant and endo/exo selectivity of its cycloaddition with cyclopentadiene (1) as well as the regioselectivity of its reaction with 2-methylbuta-1,3-diene (isoprene) (4) (Scheme 1). Results and discussion Aqueous mixtures of fluorinated alcohols as solvents in Diels– Alder reactions In order to cover uniformly the range of mole fraction composition the following mixtures (in percentage of volume of alcohol) considered were 100 95 80 50 15 and 0. The corresponding mole fractions are gathered in Table 1. As can be seen there are mixtures with less than 5% of alcohol (in mole fraction) which allows the study of the possible catalytic effects of the fluorinated alcohols.Tables 2 and 3 gather the results of the reactions of cyclopentadiene (1) with mvk (2) and (1R,2S,5R)-menthyl acrylate (3) and that of isoprene (4) with mvk (2). Reaction rates. In the case of the reaction between cyclopentadiene (1) and (1R,2S,5R)-menthyl acrylate (3) the kinetic rate constants show only a little variation with the water content of the reaction medium tending to increase with water content which indicates a positive effect of the solvent solvophobicity. J. Chem. Soc. Perkin Trans. 2 1997 Michael H. Abrahamb a b Departamento de Química Orgánica y Química Física Instituto de Ciencia de Materiales de Aragón Facultad de Ciencias Universidad de Zaragoza–C.S.I.C.E-50009 Zaragoza Spain Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street London UK WC1H 0AJ Rate endo/exo regio- and diastereo-facial selectivities of several Diels–Alder reactions were measured in a series of fluorinated alcohol–water mixtures whose solvophobicity has been determined by means of the solvophobic power (Sp) parameter. Solvophobicity is the main factor influencing the reaction rate although in some reactions hydrogen bond donating (HBD) ability may also play a role. Both solvophobicity and HBD ability are important to account for changes in endo/exo selectivity. HBD ability is the main factor responsible for the changes in regio- and diastereo-facial selectivities induced by the reaction medium.On the other hand the kinetic rate constants and endo/exo selectivity of the reaction of acrylonitrile with cyclopentadiene as well as the regioselectivity of the reaction of acrylonitrile with isoprene have been determined in 23 reaction media. The analysis of the results using empirical solvent parameters show that the reaction rate depends on solvophobic HBD and dipolarity interactions whereas endo/exo selectivity is influenced by solvophobic and dipolarity interactions and the regioselectivity only by HBD effects. Modelling of solvent effects is one of the most useful methods with which to obtain information about the mechanisms of organic reactions.1 In the last few years special attention to Diels–Alder cycloaddition has been paid due to the different solvation mechanisms involved in this process.Three main types of solute–solvent interactions have been proposed in order to explain the variations in rate and several kinds of selectivity of this reaction by modifying the reaction medium solvophobic effects hydrogen bond donor (HBD) interactions and dipolarity–polarisability.2 The increase in reaction rate observed in aqueous reaction media has been explained by the high solvophobic power (Sp) values of these media,3,4 and the use of solvents with high HBD ability namely fluorinated alcohols also favours these reactions.5–7 Solvent solvophobicity has also been invoked to explain the increase in endo/exo selectivity observed in some reaction media.4,5,8,9 HBD ability seems to be the only factor influencing the regioselectivity,7,9 and it also improves the diastereofacial selectivity.5,6 Aqueous mixtures of fluorinated alcohols would in principle present high solvophobicity together with high dipolarity and HBD ability.So it is interesting to test if the use of these mixtures improves the results in the rate and selectivities of Diels–Alder reactions. To this end we have considered the following benchmark reactions cyclopentadiene (1) with methyl vinyl ketone (mvk) (2) cyclopentadiene (1) with (1R,2S,5R)- menthyl acrylate (3) and 2-methylbuta-1,3-diene (isoprene) (4) with methyl vinyl ketone (2) [reactions (1)–(3)]. The first two reactions allow the study of solvent effects on the reaction rate and the endo/exo selectivity.The second reaction also allows us to study the effect on the diastereofacial selectivity and the third allows us to study the effect on para/meta regioselectivity. The fluorinated alcohols used were 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). However if studies on hetero-Diels–Alder reactions are excluded from consideration most of the quantitative analysis 653 (1) (2) (3) Scheme 1 Unfortunately the low solubility of the dienophile in water precludes the measure of reliable kinetic rate constants for mixtures with more than 50% in water volume which makes the assessment of the predominant factor affecting the reaction rate difficult.In the case of the reaction between cyclopentadiene (1) and mvk (2) the kinetic rate constant clearly increases with the water content of the reaction medium. In particular this increase is remarkable for mixtures with 50% or more in water volume (more than 80% in mole fraction). This points to a predominant influence of the solvophobicity on the reaction rate. In order to confirm this hypothesis the Sp values for several TFE–water and HFIP–water mixtures were determined from solubility measurements of rare gases and hydrocarbons according to the method developed by Abraham et al.10 These values are gathered in Table 4. Fig. 1 plots the Sp values of 654 J. Chem. Soc. Perkin Trans. 2 1997 Table 1 Percentages of volume and mole fractions of the fluorinated alcohols used in the aqueous mixtures Mole fraction Alcohol (vol%) xHFIP xTFE 100 95 80 50 15 0 1.000 0.765 0.406 0.146 0.029 0.000 1.000 0.824 0.497 0.198 0.042 0.000 Fig.1 Variation of the solvophobic power (Sp) of fluorinated alcohols–water mixtures with the alcohol mole fraction Fig. 2 Plot of the kinetic rate constant of the reaction between cyclopentadiene (1) and methyl vinyl ketone (2) (log k) carried out in different reaction media against the Sp empirical solvent parameter these mixtures as a function of the mole fraction of the fluorinated alcohol. As can be seen the solvophobicity of the medium falls exponentially with the proportion in alcohol. This decay is more pronounced in the case of the HFIP which indicates that the internal structure of the water is disrupted to a greater extent by HFIP i.e.the chaotropic effect is greater which can be ascribed to its higher HBD ability. When the logarithm of the kinetic rate constants of the reaction between cyclopentadiene (1) and mvk (2) is related to Sp the following regression equation is obtained [eqn. (4)]. log k = 23.167 + 2.852 (±0.514)Sp (n = 9; r = 0.903; s = 0.156; F1,7 = 30.7) (4) Table 2 Kinetic rate constants a (in l mol21 s21) and endo/exo diastereofacial and para/meta selectivities of the reactions of cyclopentadiene (1) with methyl vinyl ketone (2) and (1R,2S,5R)-menthyl acrylate (3) and of isoprene (4) with methyl vinyl ketone carried out in several aqueous mixtures of TFE 4 + 2 1 + 3 1 + 2 k/1024 l mol21 s21 TFE (vol%) k/1023 l mol21 s21 endo/exo endo2R/endo2S para/meta (7 + 8)/(9 + 10) (8/7) (12/11) endo/exo (5/6) 2.10 2.21 2.30 8.24 8.30 8.67 4.6 4.2 3.6 3.0 2.7 2.5 1.48 1.45 1.47 1.45 1.30 1.27 6.6 6.9 6.9 6.6 5.6 3.1 10.3 10.1 11.7 12.1 16.5 16.5 100 95 80 50 15 0 2.67 bb 19.06 bb a Determined by gas chromatography.b Solubility of the reagents is too low to obtain reliable values. Table 3 Kinetic rate constants a (in l mol21 s21) and endo/exo diastereofacial and para/meta selectivities of the reactions of cyclopentadiene (1) with methyl vinyl ketone (2) and (1R,2S,5R)-menthyl acrylate (3) and of isoprene (4) with methyl vinyl ketone carried out in several aqueous mixtures of HFIP 4 + 2 1 + 3 1 + 2 endo/exo (5/6) endo/exo 2R/endo2S endo para/meta (7 + 8)/(9 + 10) (8/7) (12/11) k/1024 l mol21 s21 HFIP (vol%) k/1023 l mol21 s21 1.96 2.21 2.10 5.78 5.22 6.19 8.5 7.0 5.0 4.7 3.8 2.5 1.78 1.76 1.58 1.54 1.55 1.27 7.2 7.5 7.3 7.3 7.5 3.1 10.0 11.1 11.2 11.7 12.3 16.5 100 95 80 50 15 0 2.46 bb 11.19 65.95 b a Determined by gas chromatography.b Solubility of the reagents is too low to obtain reliable values. If we examine the corresponding plot of log k vs. Sp (Fig. 2) it is apparent that the data from the aqueous TFE mixtures lie on a different line to those of the aqueous HFIP mixtures.Taking each series separately the regression models signifi- cantly improve [eqns. (5) and (6)]. log k (TFE) = 22.685 + 1.838 (±0.216)Sp (n = 4; r = 0.986; s = 0.036; F1,2 = 72.3) (5) log k (HFIP) = 23.656 + 3.776 (±0.405)Sp (n = 5; r = 0.983; s = 0.097; F1,3 = 86.8) (6) In both series there is a fair linear correlation between the solvophobicity of the medium and the reaction rate which indicates that solvophobicity is the main factor influencing this reaction feature. However the fact that the slopes are different may indicate that there are other solvent properties (probably the HBD ability) that can also play a role. Fig. 3 Plot of the endo/exo selectivities of the reaction between cyclopentadiene (1) and methyl vinyl ketone (2) (log endo/expo) carried out in different reaction media against the Sp empirical solvent parameter to reach a maximum in pure water.This indicates that for this dienophile solvophobicity is the main factor responsible for the variation observed in the endo/exo selectivity in agreement with previously reported results using multiparametric regression models.9 As in the case of the reaction rate regression analyses using Sp as the independent variable agree with this interpretation [eqn. (7)]. log (5/6) = 0.918 + 0.314 (±0.033)Sp (n = 11; r = 0.954; s = 0.024; F1,9 = 91.8) (7) Endo/exo selectivity. In the case of the reaction of cyclopentadiene (1) with (1R,2S,5R)-menthyl acrylate (3) the endo/exo selectivity (7 + 8/9 + 10) remains almost constant within each series of reaction media except in the case of pure water being used as the reaction medium.In this case the observed endo/exo selectivity decreases to a value similar to that obtained when the reaction is carried out in low polar media. This is undoubtedly due to the low solubility of the dienophile in water which leads to the existence of two phases in this solvent. Most of the reaction occurs in the organic phase leading to the low selectivities observed. As a conclusion changes in solvophobicity do not seem to be important to determine the final endo/exo selectivity. The reactions carried out in aqueous mixtures of HFIP are slightly more selective than those carried out in aqueous mixtures of TFE which indicates that the HBD ability of the reaction medium has a small but positive influence on this kind of selectivity.Unlike the case of the reaction rate however the plot of log (endo/exo) vs. Sp (Fig. 3) does not indicate the necessity of splitting the data into two separate series and indeed when the In the case of the reactions of mvk (2) the behaviour is quite different. The endo/exo selectivity (5/6) remains constant for reaction media containing 50% or less water and then increases 655 J. Chem. Soc. Perkin Trans. 2 1997 Table 4 Solvophobic power (Sp) values of the fluorinated alcohol– water mixtures at several mixture compositions Sp Sp xHFIP Alcohol (vol%) xTFE 0.35 0.37 0.40 0.43 0.45 0.48 1.000 0.606 0.406 0.285 0.204 0.146 0.31 0.35 0.36 0.40 0.45 0.52 1.000 0.690 0.497 0.366 0.270 0.198 100 90 80 70 60 50 40 30 0.54 0.59 0.71 1.00 0.102 0.068 0.041 0.000 0.60 0.71 0.87 1.00 0.141 0.096 0.058 0.000 20 0 Fig.4 Plot of the para/meta regioselectivity of the reaction between isoprene (4) and methyl vinyl ketone (2) carried out in different reaction media against the mole fraction of fluorinated alcohol in the reaction media regressions are repeated for each separate series the results do not significantly improve [eqns. (8) and (9)]. log (5/6) (TFE) = 0.923 + 0.316 (±0.041)Sp (n = 6; r = 0.967; s = 0.027; F1,4 = 58.5) (8) log (5/6) (HFIP) = 0.923 + 0.289 (±0.034)Sp (n = 6; r = 0.973; s = 0.019; F1,4 = 72.1) (9) Para/meta regioselectivity.The para/meta regioselectivity (12/ 11) of the reaction between isoprene (4) and mvk (2) uniformly increases with the proportion of fluorinated alcohol in the reaction medium and when keeping fixed the proportion of water it is also greater for HFIP than for TFE mixtures. In fact there is a linear dependence between this kind of selectivity and the mole fraction of alcohol in the mixture (Fig. 4). This result points to the HBD ability as the main factor influencing this selectivity which is in agreement with previously reported results. Thus the reaction between isoprene and acrolein carried out in toluene–HFIP mixtures,7 also displays the same behaviour (Fig.4). Furthermore the application of empirical 9 and theoretical 11 solvent models also supports this conclusion in the case of other solvents and aqueous mixtures. It is important to note that the HBD ability of water (a = 1.17) is not suf- ficient to induce an increase of para/meta regioselectivity with respect to an ‘inert’ solvent such as hexane ( para/meta = 2.21).9 Diastereofacial selectivity. The endo2R/endo2S diastereofacial selectivity (8/7) of the reaction of cyclopentadiene (1) with (1R,2S,5R)-menthyl acrylate (3) increases with the proportion of alcohol in the reaction medium. As happened in the para/ meta regioselectivity the selectivity obtained with HFIP is also greater than that obtained with TFE when both fluorinated 656 J.Chem. Soc. Perkin Trans. 2 1997 Fig. 5 Plot of the diastereofacial selectivity of the reaction between cyclopentadiene (1) and (1R,2S,5R)-menthyl acrylate (3) carried out in different reaction media against the mole fraction of fluorinated alcohol in the reaction media alcohols are in the same proportion in the mixture. However unlike the para/meta regioselectivity the variation in diastereofacial selectivity is not linear with the mole fraction of fluorinated alcohol. In the case of TFE (Fig. 5) the endo2R/endo2S selectivity increases with the proportion of alcohol until a mole fraction of ca. 0.2 and then remains practically constant until the pure alcohol. In the case of HFIP the diastereofacial selectivity rapidly increases with the proportion of fluorinated alcohol.Then it remains constant until a mole fraction of ca. 0.4 in HFIP and finally it displays a further increase until the pure alcohol is used as a solvent. This behaviour is completely different from that observed in the case of the reaction carried out in toluene– HFIP mixtures 6 (Fig. 5). In this case the diastereofacial selectivity uniformly increases with the proportion of fluorinated alcohol in a practically linear form. These results point to a non-negligible role of the co-solvent in this kind of selectivity. The diastereofacial selectivity is always higher in aqueous mixtures than in toluene–HFIP mixtures. A possible explanation of this result comes from the different polarity of water and toluene.Thus when water is the co-solvent the dienophile– HFIP hydrogen-bonded species are solvated in a highly polar medium favouring the charge transfer and then the behaviour of HFIP as a true Lewis acid. However toluene is a medium of low polarity and the dienophile–HFIP hydrogen-bonded species are poorly solvated giving rise to a lesser charge transfer between them. Only the increasing of the HFIP in the mixture leads to a global increasing of polarity and hence to a greater role of the HFIP as a mild Lewis acid. This further increase in diastereofacial selectivity as observed in the aqueous mixtures of HFIP may be due to the existence of two molecules of HFIP simultaneously solvating a single molecule of dienophile a fact which has been reported to happen in the case of solutions of mvk in HFIP,7 but does not happen in the case of the less HBD TFE.Solvent eVects on Diels–Alder reactions of acrylonitrile In order to cover a wide range of solvent properties we selected a set of 23 reaction media with different solvophobicity dipolarity–polarisability and hydrogen-bond donor (HBD) ability as expressed by the Sp p* and a empirical solvent parameters,1 respectively. The reason for choosing these parameters is that they have already been successfully used to explain the solvent effects observed in the Diels–Alder reactions of carbonyl-containing dienophiles.2 Furthermore they have Table 5 Empirical solvent parameter values and experimental responses for the reactions of acrylonitrile (13) with cyclopentadiene (1) (kinetic rate constant and endo/exo selectivity) and with isoprene (4) (para/meta regioselectivity) carried out in several reaction media Solvent (vol%) Hexane Perfluorohexane Toluene Ethyl acetate Acetone DMFa Acetonitrile Dioxane Methanol DMSOb Dichloromethane Propylene carbonate Acetone (80%) Acetone (40%) 1,4-Dioxane (60%) 1,4-Dioxane (50%) 1,4-Dioxane (30%) Methanol (70%) Methanol (60%) Methanol (30%) Water TFE HFIP log k = 25.51 + 0.95 (±0.33)Sp + s = 0.22 r = 0.961 a N,N9-Dimethylformamide.b Dimethyl sulfoxide. c Value from ref. 12. been determined for many organic solvent–water mixtures which are practically interesting reaction media.Table 5 gathers the 23 solvents and solvent mixtures studied together with their corresponding empirical solvent parameter values and the results obtained in the Diels–Alder reactions of acrylonitrile (13) with cyclopentadiene (1) and isoprene (4) (Scheme 1). Reaction rate. The regression analyses carried out using the logarithm of the rate kinetic constant of the reaction between cyclopentadiene (1) and acrylonitrile (13) as the dependent variable show that the three empirical parameters considered are statistically significant leading to eqn. (10). 0.80 (±0.18)p* + 0.55 (±0.11)a (10) Standardised coefficients:† 0.32 0.44 and 0.43 n = 18 As can be seen the most important factors in determining the reaction rate are the dipolarity–polarisability and the HBD ability both having a similar standardised regression coef- ficient whereas the solvophobicity lies on a second plane.This result is surprising for two reasons. First for all previous studies dealing with solvent effects on the Diels–Alder reactions solvophobicity was always found to be the main factor influencing the reaction rate. Secondly it is the first time that polarity– polarisability appears as an important factor in determining the reaction rate of a Diels–Alder reaction. The relatively minor role of the solvophobic effects on the rate of this reaction has been previously described by Rideout and Breslow. Thus the change of isooctane by water as a solvent led to an acceleration of this reaction by a factor of 31.2 whereas the same change of the reaction medium provoked an acceleration by a factor of 740.7 when methyl vinyl ketone was used as the dienophile.12 However our results show that the role of solvophobicity is probably greater than that described by † The standardised coefficient is defined as bst = bsX/sy where b is the regression coefficient sX the standard deviation of the independent variable and sy the standard deviation of the dependent variable.The values of bst allow a direct comparison of the relative importance of each variable regardless of its units. p* 20.08 20.48 0.49 0.55 0.71 0.88 0.75 0.55 0.60 1.00 0.82 0.83 —— 0.92 0.99 1.09 0.91 0.98 1.11 1.09 0.73 0.65 F3,14 = 56.8 ( p < 0.0001) Sp k 1026/cm3 mol21 s21 1.05 (±0.46) 2.44 (±0.62) 0.0091 0.0000 0.0000 0.0635 0.1267 0.1384 — 10.13 (±1.67) 13.52 (±2.46) 14.89 (±2.55) 17.18 (±2.73) 1942 (±1.26) 0.2167 0.0794 0.1998 0.2268 0.0000 — 25.00 (±5.78) 26.00 (±6.55) 28.08 (±9.33) 31.08 (±8.73) 47.91 (±4.82) 154.84 (±41.78) 0.2390 0.6080 0.3900 0.5210 0.7550 0.4460 172.74 (±21.47) 201.96 (±52.58) 272.27 (±14.16) 167.69 (±16.46) 201.72 (±33.26) 290.20 (±16.09) a 0.00 0.00 0.00 0.00 0.08 0.00 0.19 0.00 0.93 0.00 0.30 0.00 —— 0.57 0.61 0.74 0.91 0.87 0.92 1.17 1.51 1.96 0.5310 0.8080 1.0000 0.3250 0.2800 539 c 127.80 (±18.01) 260.16 (±31.33) these authors.Thus the change of hexane by a mixture of methanol–water 30 70 leads to a ca. 300 times acceleration of the reaction rate i.e. one order of magnitude more than that previously described and closer to that observed for methyl vinyl ketone. The question remains as to why the Sp regression coefficient is the less important one. A possible explanation lies in the high cross-correlations between empirical solvent parameters. Thus Sp is highly correlated both with p* (r = 0.69) and with a (r = 0.58) so that part of the solvophobic effect on the reaction rate may be included in the regression coefficients of p* and a. In fact if we include the kinetic rate constant value reported by Rideout and Breslow for the reaction carried out in pure water,12 the following regression equation is obtained [eqn.(11)]. log k = 25.53 + 1.39 (±0.32)Sp + Standardised coefficients 0.47 0.33 and 0.35 n = 19 As can be seen in this equation Sp is the most important factor in explaining changes in reaction rate whereas the relative importance of p* and a decreases although their regression coefficients do not change very much. As a conclusion solvophobicity is the main solvent feature influencing the reaction rates as happens for carbonyl-containing dienophiles. Previous theoretical studies agree with the positive influence of the medium polarity 11 and HBD ability 11,13 of the solvents on the reaction rate. The acceleration of this reaction by means of HBD solvents agrees with the known behaviour of this kind of media as mild Lewis acids above all in the case of fluorinated alcohols.However it is difficult to assert that solvent dipolarity influences the reaction rates only on the basis of experimental results because the most solvophobic and HBD solvents are also highly polar. In the case of carbonyl-containing dienophiles the theoretical calculations predict a negative influence of solvent dipolarity on the reaction rate,11 which is difficult to detect experimentally because the strongly positive effects of solvophobicity and HBD ability mask this influence. However in the case of acrylonitrile this effect can be detected given that para/meta (16/17) endo/exo (14/15) 2.74 (±0.13) — 2.78 (±0.09) 3.02 (±0.09) 2.85 (±0.13) 2.83 (±0.15) 0.99 (±0.01) 1.13 (±0.01) 1.12 (±0.01) 1.53 (±0.04) 1.74 (±0.02) 1.70 (±0.03) 3.17 (±0.19) 3.13 (±0.08) 3.30 (±0.17) — 3.54 (±0.15) 3.32 (±0.18) 1.94 (±0.04) 1.45 (±0.02) 1.82 (±0.04) 2.04 (±0.05) 1.44 (±0.03) 1.94 (±0.04) 2.67 (±0.05) 2.57 (±0.28) 3.16 (±0.08) 3.38 (±0.02) 3.47 (±0.15) 3.48 (±0.27) 1.81 (±0.08) 2.15 (±0.04) 1.91 (±0.06) 2.08 (±0.08) 2.23 (±0.07) 1.98 (±0.06) 3.17 (±0.14) 3.51 (±0.02) 3.76 (±0.02) 4.55 (±0.21) 5.41 (±0.24) 2.05 (±0.07) 2.26 (±0.05) 2.34 (±0.11) 1.73 (±0.03) 1.60 (±0.04) 0.70 (±0.21)p* + 0.52 (±0.13)a (11) s = 0.26 r = 0.961 F3,15 = 61.0 ( p < 0.0001) 657 J.Chem. Soc. Perkin Trans. 2 1997 Fig. 6 Plot of the endo/exo selectivities of the reaction between cyclopentadiene (1) and acrylonitrile (13) [log (endo/exo)] carried out in different reaction media against the Berson’s empirical solvent parameter W it adds to the other two thus confirming the theoretical predictions.11 Endo/exo selectivity. The results of the corresponding regression analysis show a slightly poor determination coefficient (r = 0.927). Only Sp and p* parameters are significant for the endo/exo selectivity (14/15) of the reaction between cyclopentadiene (1) and acrylonitrile (13) according to eqn. (12). log (14/15) = 0.07 + 0.15 (±0.05)Sp + 0.16 (±0.03)p* (12) s = 0.04 r = 0.927 Standardised coefficients 0.41 and 0.60 n = 20 F2,17 = 52.0 ( p < 0.0001) The importance of the solvophobic interactions on the endo/ exo selectivity agrees with the results obtained for the reactions of cyclopentadiene with other dienophiles.5,9 The values of standard coefficients show that p* is the most significant parameter although Sp is also significant.The low importance of solvophobic interactions in this reaction contrasts with the greater importance of Sp on the endo/exo selectivities of cyclopentadiene with methyl vinyl ketone and methyl acrylate.9 However this result agrees with the smaller difference between the volumes of the endo and exo transition states for the reaction of acrylonitrile (DDV‡ = 0.22 cm3 mol21) relative to that of methyl acrylate (DDV‡ = 0.52 cm3 mol21).14 The rise of endo/exo selectivity by increasing the medium polarity is also supported by theoretical calculations.11,15 Finally the lack of significance of the a parameter indicates that the acceleration of this reaction by means of HBD solvents is similar in both endo and exo approximations of the reactants.This behaviour is also different from that described for carbonyl-containing dienophiles. For these dienophiles the HBD ability of the solvent is always significant. This difference can be related to the lower basicity of nitriles compared with ketones and esters. The different sensitivity of acrylonitrile and methyl acrylate to solvent effects can be easily pointed out if one considers the plot of log (endo/exo) of the reaction between acrylonitrile and cyclopentadiene versus Berson’s W1 (Fig.6) which is defined as the endo/exo selectivity obtained in the reaction of cyclopentadiene with methyl acrylate carried out in a given solvent. As can be seen non-hydroxylic and hydroxylic solvents lie either on different straight lines or on a single curved line. Moreover fluorinated alcohols lie outside both correlation lines which 658 J. Chem. Soc. Perkin Trans. 2 1997 indicates that the relative weight of dipolarity solvophobicity and HBD ability is different for the two systems. Regioselectivity. The regression analysis shows that the a parameter is the only parameter significant for the para/meta selectivity (16/17) of the reaction between isoprene (4) and acrylonitrile (13) [eqn.(13)]. (13) log (16/17) = 0.46 + 0.11 (±0.01)a s = 0.03 r = 0.885 n = 19 F1,17 = 61.7 (p < 0.0001) The regression coefficient found in this case for the a parameter is smaller than that obtained for the reactions of the same diene with methyl vinyl ketone (0.22) and methyl acrylate (0.17).9 This result agrees with the lower sensitivity of acrylonitrile to Lewis acids in the Diels–Alder reaction relative to the other dienophiles. Thus the reaction of 9-methylanthracene with methyl acrylate is accelerated 2.2 × 105 times by using GaCl3 as a catalyst whereas the reaction of acrylonitrile with the same diene is accelerated by a factor of 1.5 × 105 under the same conditions.16 The regioselectivity of the reaction between isoprene and acrylonitrile can be increased by using Lewis acids.17 For this reason the role of the a parameter can be explained by means of the behaviour of HBD solvents as mild Lewis acids.When only protic solvents are considered a better determination coefficient is found [eqn. (14)]. Neither p* nor Sp par- (14) log (16/17) = 0.39 + 0.17 (±0.02)a s = 0.02 r = 0.953 n = 10 F1,8 = 78.9 (p < 0.0001) ameters are significant in this regression analysis. The negligible effect of dielectric interactions agrees with the low effect of polarity medium calculated by means of theoretical calculations. 11 However the lack of significance of the Sp parameter agrees with the experimental results found for the cycloaddition between isoprene and methyl acrylate.9 Experimental Solubility measurements Solubility of rare gases He Ar and of CH4 were measured by a saturation method using an apparatus described in detail elsewhere and which is based on a design by Ben-Naim and Baer.18 It consists essentially of a solution vessel (ca.100 cm3) containing the liquid a burette system and a mercury manometer for the control and measurement of the gas pressure. The temperature of the air thermostat bath holding the whole apparatus was controlled to within ±0.2 8C and temperature control of the solution vessel was to within ±0.05 8C. The experimental technique is based on the determination of the volume of wet gas (saturated with vapour of liquid) which dissolves in a known mass of solvent at a constant pressure.The total pressure was chosen so that the partial pressure of the gas under study was ca. 101.33 kPa. All the gases were from Air Liquide España and their mole percentage purities where He 99.995; Ar 99.9990; CH4 99.95. TFE and HFIP were Janssen products with 99+ and 99.5+% purity respectively. The data treatment for determining solubility is a modifi- cation 19 of the data reduction method proposed by Bo et al.20 The modification takes into account the characteristics of our apparatus especially the fact that the temperature of the gas phases in the burettes is slightly higher than that of the vessel containing the liquid. Ideal behaviour of the wet gas has been assumed when determining the solubility of gases in the TFE–water and HFIP– water mixtures.The effect of considering the real behaviour of the gas when TFE or HFIP are used as pure solvents and the differences obtained are within the experimental error. Compositions of the liquid absorbing gas are determined Table 6 Amounts of reagents and solvent volume used for the reactions of cyclopentadiene (1) with methyl vinyl ketone (2) and (1R,2S,5R)-menthyl acrylate (3) and of isoprene (4) with methyl vinyl ketone Reaction medium Dienophile/ mmol Diene/ mmol V/ml 0.50 0.50 1.50 1.50 88 100 0.50 1.50 Pure organic solvents Alcohol–water mixtures (up to 50% water) Alcohol–water mixtures (more than 50% water) 100 0.33 1.00 Pure water Table 7 Solvent volumes (in ml) used in the aqueous reaction media of the reactions of acrylonitrile (13) Isoprene reactions Cyclopentadiene reactions Solvent (vol%) 15 35 50 32 32 32 22 32 10 15 40 32 12 17 10 30 250 250 1,4-Dioxane (60%) 1,4-Dioxane (50%) 1,4-Dioxane (30%) Methanol (70%) Methanol (60%) Methanol (30%) Acetone (80%) Acetone (40%) Water from vapour pressure before the solution process and verified through density measurements of the mixtures after the solution of gas.Reaction procedure Organic solvents were purified and dried according to standard procedures. The reactions were monitored by gas chromatography (FID from Hewlett-Packard 5890 II chromatograph cross-linked methyl silicone column 25 m × 0.22 mm × 0.33 mm). Cyclopentadiene (1) with methyl vinyl ketone (2) A thermostatted (30 ± 1 8C) solution of the corresponding amounts of diene and dienophile (Table 6) together with a small amount of toluene used as internal standard was stirred magnetically and monitored by GC helium as carrier gas (18 psi‡) oven temperature program 100 8C (1 min)–25 8C min21–125 8C (4 min); retention times toluene 2.5 min exo cycloadduct (6) 4.9 min endo cycloadduct (5) 5.2 min.Calibration line [adducts]/ [toluene] = 0.9024 × (peak areaadducts/peak areatoluene) 2 0.0241 (r = 1.000). Cyclopentadiene (1) with (1R,2S,5R)-menthyl acrylate (3) A thermostatted solution of diene and dienophile was stirred magnetically and monitored by GC helium as carrier gas (18 psi) oven temperature program 190 8C (1 min)–2 8C min21– 180 8C (0 min)–1 8C min21–170 8C (5 min); retention times (1R,2S,5R)-menthyl acrylate (3) 3.7 min exo cycloadducts (9 + 10) 17.0 min endo2S cycloadduct (7) 17.6 min endo2R cycloadduct (8) 18 min.Isoprene (4) with methyl vinyl ketone (2). A thermostatted solution of diene and dienophile was stirred magnetically and monitored by GC helium as carrier gas (18 psi) oven temperature program 50 8C (3 min)–25 8C min21–90 8C (15 min); retention times mvk (2) 2.4 min meta cycloadduct (11) 15.0 min para cycloadduct (12) 15.3 min. Acrylonitrile (13) with cyclopentadiene (1). In a typical run in non-aqueous reaction media 0.053 g (1 mmol) of acrylonitrile (13) dissolved in the corresponding reaction medium (2 ml) were added to a thermostatted (30 ± 1 8C) solution of 0.099 g ‡ 1 psi = 6895 Pa.(1.5 mmol) of freshly distilled cyclopentadiene (2) and 0.04 g (0.4 mmol) of 1,2-dichloroethane used as internal standard in the same solvent (2 ml). In the case of aqueous reaction media the low solubility of cyclopentadiene obliges the use of greater reaction volumes (Table 7). The reaction was monitored by GC helium as carrier gas (17 psi) oven temperature program 50 8C (3 min)–25 8C min21–90 8C (10 min). Retention times 2.8 min 1,2-dichloroethane 11.2 min endo cycloadduct (14) 12.4 min exo cycloadduct (15). Acrylonitrile (13) with isoprene (3). In a typical run in nonaqueous reaction media 0.106 g (2 mmol) of acrylonitrile (1) dissolved in the corresponding reaction medium (2 ml) were added to a thermostatted (30 ± 1 8C) solution of 0.204 g (3 mmol) of freshly distilled cyclopentadiene (2) in the same solvent (2 ml).In the case of aqueous reaction media the low solubility of isoprene obliges the use of greater reaction volumes (Table 7). Reactions were monitored by GC helium as carrier gas (17 psi) oven temperature program 50 8C (3 min)– 25 8C min21–80 8C (15 min). Retention times 17.2 min para cycloadduct (16) 16.8 min meta cycloadduct (17). Conclusions Solvent solvophobicity is the main factor in increasing the rate of Diels–Alder reactions of both carbonyl-containing and nitrile-containing dienophiles with both kinds of dienophiles the role of hydrogen bond interactions being much less important. However this solvent property is the main factor responsible for the changes observed in regio- and diastereo-facial selectivities.The influence of the solvent on the endo/exo selectivity is more dependent on the nature of the dienophile and it can be increased by the solvophobicity dipolarity– polarisability and HBD ability of the solvent. All the results obtained agree with previous theoretical studies and show that the nature of the dienophile is of prime importance to determine the relative influence of the different solvation mechanisms on each reaction feature. The choice of the reaction medium depends on what is more important in each case either high rate or high selectivities. Although there is not a cooperative effect of water and fluorinated alcohols the use of their mixtures may represent a reasonable compromise between both reaction features.Acknowledgements This work was made possible by the generous financial support of the Comisión Interministerial de Ciencia y Tecnología (Project MAT96-1053). We thank Professor Christian Reichardt for his valuable suggestions and helpful discussions. References 1 C. Reichardt Solvents and Solvent Effects in Organic Chemistry VCH Weinheim 1988. 2 C. Cativiela J. I. García J. A. Mayoral and L. Salvatella Chem. Soc. Rev. 1996 209. 3 (a) H.-J. Schneider and N. K. Sangwan J. Chem. Soc. Chem. Commun. 1986 1781; (b) N. K. Sangwan and H.-J. Schneider J. Chem. Soc. Perkin Trans. 2 1989 1223; (c) C. Cativiela J. A. Mayoral A. Avenoza J. M. Peregrina and M. A. Roy J. Phys. Org. Chem. 1990 3 414. 4 C. Cativiela J. I. García J. A. Mayoral A. Avenoza J. M. Peregrina and M. A. Roy J. Phys. Org. Chem. 1991 4 48. 5 C. Cativiela J. I. García J. A. Mayoral A. J. Royo L. Salvatella X. Assfeld and M. F. Ruiz-López J. Phys. Org. Chem. 1992 5 230. 6 C. Cativiela J. I. García J. A. Mayoral A. J. Royo and L. Salvatella Tetrahedron:Asymmetry 1993 4 1613. 7 C. Cativiela J. I. García J. A. Mayoral and L. Salvatella Can. J. Chem. 1994 72 308. 8 H.-J. Schneider and N. K. Sangwan Angew. Chem. Int. Ed. Engl. 1987 26 896. 9 C. Cativiela J. I. García J. A. Mayoral and L. Salvatella J. Chem. Soc. Perkin Trans. 2 1994 847. J. Chem. Soc. Perkin Trans. 2 1997 659 10 M. H. Abraham P. L. Grellier and R. A. McGill J Chem. Soc. Perkin Trans. 2 1988 339. 11 C. Cativiela V. Dillet J. I. García J. A. Mayoral M. F. Ruiz-López and L. Salvatella J. Mol. Struct. (THEOCHEM) 1995 331 37. 12 D. C. Rideout and R. Breslow J. Am. Chem. Soc. 1980 102 7816. 13 J. F. Blake D. Lim and W. L. Jorgensen J. Org. Chem. 1994 59 803. 14 T. Asano and W. J. Le Noble Chem. Rev. 1978 78 407. 15 T. Karcher W. Sicking J. Sauer and R. Sustmann Tetrahedron Lett. 1992 33 8027. 16 V. D. Kiselev and A. I. Konovalov Usp. Khim. 1989 58 383; Russ. Chem. Rev. 1989 58 230. 660 J. Chem. Soc. Perkin Trans. 2 1997 17 J. C. Soula D. Lumbroso M. Hellin and F. Coussemant Bull. Soc. Chim. Fr. 1966 2065. 18 A. Ben-Naim and S. Baer Trans. Faraday Soc. 1963 59 2735. 19 F. Gibanel M. C. López F. Royo V. Rodríguez and J. S. Urieta J. Solution Chem. 1994 23 1061. 20 S. Bo R. Battino and E. Wilhelm J. Chem. Eng. Data 1993 38 611. Paper 6/01717G Received 11th March 1996 Accepted 29th November 1996
ISSN:1472-779X
DOI:10.1039/a601717g
出版商:RSC
年代:1997
数据来源: RSC
|
|