I THE EFFECT OF HALOGEN ATOMS UPON THE SN2 REACTIVITY OF OTHER HALOGEN ATOMS ATTACHED TO THE SANE CARBON ATOM II A STUDY OF THE RATE OF PROTON TRANSFER REACTIONS A THESIS Presented to the Faculty of the Graduate Division by Cyrus Henry Thomas In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the School of Chemistry Georgia Institute of Technology June 1953 I lilt hiikECT OF HALOGEN ATOMS UPON THE SN2 REACTIVITY OF OTHER HALOGEN ATOMS ATTACHED TO THE SAME CARBON ATOM II A STUDY OF THE RATE OF PROTON TRANSFER REACTIONS Approved: r • V • Date approved by Chairman: /14 4,ld / 95-3 ii Acknowledgement I wish to express my sincere appreciation to Dr. Jack Hine, not only for the suggestion of the problems and his valuable aid and guidance, but also for the confidence which he displayed in my abilities by granting me a Fellowship and a Research Assistantship. Secondly, I wish to thank the Research Corporation of New York and the Atomic Energy Commission for the funds which they supplied for these investigations. Thirdly, I wish to thank my wife for the constant encouragement she has given me and the never-ending patience she has displayed, without which I may never have completed this work. iii TABLE OF CONTENTS ACKNOWLEDGEMENTS LIST OF TABLES LIST OF ILLUSTRATIONS SUMMARY PART I Chapter I INTROIUCTION 2 II PROCEDURE 5 Experimental Preparation and Purification of Reagents III DISCUSSION OF RESULTS 21 IV CONCLUSIONS 33 V RECOMMENDATIONS 34 APPENDIX A - SAMPLE CALCULATIONS 35 APPENDIX B - TABLES 44 APPENDIX C - GRAPHS 88 BIBLIOGRAPHY 97 iv PART II Page Chapter I INTRODUCTION 100 II INSTRUMENTATION AND EQUIPMENT io6 III PROCEDURE 118 Experimental Preparation and Purification of Reagents IV DISCUSSION OF RESULTS 126 V CONCLUSIONS 132 APPENDIX A - SAMPLE CALCULATIONS 133 BIBLIOGRAPHY 140 VITA 142 V LIST OF TABTRS PART I Table Page 1. Determination of Acetone Interference 7 2. Summary of Results for the Reaction RX + Y- RY + X- 23 3. Alkyl Bromide Plus Iodide Ion 26 4. Alkyl Iodide Plus Methoxide Ion 28 5. Alkyl Bromide Plus Methoxide Ion 30 6. Densities of Compounds Used 45 7. cH3I + NaOCH3 in Absolute Methanol at 20.3°C. 46 8. m131 + Na0CH3 in Absolute Methanol at 50 °C. 47 9. cH2cli + NaOCH3 in Absolute Methanol at 20.3°C. 48 10. CH2C1I + NaOCH3 in Absolute Methanol at 50 °C. 49 11. CH2BrI + NaOCH3 in Absolute Methanol at 20.3 °C. 50 12. CH2BrI + NaOCH3 in Absolute Methanol at 50 °C. 52 13. CH2I2 + NaOCH3 in Absolute Methanol at 20.3 °C. 54 14. CH2I2 + NaOCH3 in Absolute Methanol at 50°C. 56 15. CH3Br + NaOCH3 in Absolute Methanol at 20.3 °C. 57 16. CH3Br + NaOCH3 in Absolute Methanol at 50°C. 58 17. CH3CH2Br + NaOCH3 in Absolute Methanol at 20.3 ° C. 59 18. CH3CH2Br + NaOCH3 in Absolute Methanol at 50 °C. 60 19. CH2FBr + NaOCH3 in Absolute Methanol at 20.3 °C. 61 20. CH2FBr + NaOCH3 in Absolute Methanol at 50 °C. 62 21. CH2C1Br + NaOCH3 in Absolute Methanol at 20.3 °C. 63 vi 22. CH2C1Br + NaOCH3 in Absolute Methanol at 36°C. 64 23. CH2C1Br + NaOCH3 in Absolute Methanol at 50°C. 65 24. CH2Br2 + NaOCH3 in Absolute Methanol at 20.3°C. 66 25. CH2Br2 + NaOCH3 in Absolute Methanol at 36 °C. 67 26. CH2Br2 + NaOCH3 in Absolute Methanol at 50 °C. 68 27. CH2C12 + NaOCH3 in Absolute Methanol at 50 °C. 70 28. CH3Br + NaI in Acetone at 0 °C. 71 29. CH3CH2Br + NaI in Acetone at 20.3 °C. 72 30. CH3CH2Br + NaI in Acetone at 50 °C. 73 31. CH2BrF + Nal in Acetone at 20.3 °C. 74 32. CB2BrF + NaI in Acetone at 50 °C. 75 33. CH2C1Br + NaI in Acetone at 20.3 °C. 76 34. CH2C1Br + NaI in Acetone at 36°C. 77 35. CH2C1Br + Nal in Acetone at 50 °C. 78 36. CH2Br2 + NaI in Acetone at 20.3°C. 79 37. CH2Br2 + NaI in Acetone at 36°C. 80 38. CH2Br2 + NaI in Acetone at 50°C. 81 39. CH2BrI + Nei in Acetone at 20.3 °C. 82 40. CH2BrI + NaI in Acetone at 50 °C. 83 41. CH2C12 + Nei in Acetone at 50 °C. 84 42. CH2C12 + NaI in Acetone at 60 °C. 85 43. CH2C1I + NaI in Acetone at 50 °C. 86 44. CH2C12 + NaOCH3 in Absolute Methanol 87 vii PART II Table Page 1. Calibration Data for Micropipette 114 2. Data Obtained by Orr 126 3. Calculated Rate Constants 127 4. Calculated Equilibrium Percentages 128 5. Results of Exchange Between Heavy Water and Ethanol 130 6. Results of Deuterium Exchange Reactions 131 viii LIST OF ILLUSTRATIONS PART I Figure Page 1. Densities of Halomethanes 89 2. Log of Rate Constant versus the Reciprocal of the Absolute Temperature 90 3. Relationship Between Rate of Reaction of Alkyl Bromides with NaI and NaOCH3 91 4. CH2BrI + NaOCH3 in Methanol at 20.3 °C. 92 5. cH2I2 + NaOCH3 in Methanol at 20.3 °C. 93 6. CH3CH2Br + NaI in Acetone at 20.3 °C. 91 . 7. CH2BrI + NaI in Acetone at 20.3 °C. 95 8. CH2BrI + NaI in Acetone at 50 °C. 96 ix PART II Figure Page 1. Mercury-Toluene Thermoregulator 108 2. Micropipette 110 3. Micropipette Mounting Assembly 112 4. Calibration Curve for Micropipette 113 5. Infrared Absorption Spectra for Partially Deuterated t-Butylalcohol and t-Butylalcohol 115 6. Infrared Absorption Spectra for Ethylamine and Partially Deuterated Ethylamine 116 7. Calibration Curve for Determination of Ethanol 117 Summary Part I Since one of the most important reactions in organic chemistry is the nucleophilic displacement reaction upon carbon, of the type: RX + Y --is RY + X , it is of considerable interest to determine the effect of various groups in R upon the reaction. It is known for instance, that methyl groups on the alpha carbon atom of R have an inhibiting effect upon the SN2 reactivity and an enhancing effect upon SN1 reactivity. It has been shown semi-quantitatively that a halogen atom on the alpha carbon decreases SN2 reactivity but it is not known which halogens have the greatest effect nor is the extent of this effect known. Hence, we were interested in determining the effect of alpha halogen atoms upon the SN2 reactivity of other halogen atoms attached to the same carbon atom under various conditions and with various reagents. One method of attack was through the well known reaction of sodium iodide in acetone upon the dihalo methanes, for example: C1CH2Br + NaI --is C1CH2I + NaBr. In a case such as this the bromine atom is the one assumed to react since in all known cases bromine in an organic molecule reacts many times faster than chlorine. The reaction was followed through the rate of xi disappearance of the sodium iodide by titration of the iodide ion with potassium iodate in the presence of cold concentrated hydrochloric acid, according to the equation: 21 - + 103 + 6HC1 31C1 + 3H20 + 3C1 - The second method of attack was through the reaction of sodium methoxide in absolute methanol with the dihalo methanes, for example: ow NaOCH3 C1CH2Br + NaOCH3 Sl C1CH2OCH3 CH2(0CH3)2 Fast Here again it was assumed that the bromine atom reacts first and since it was shown in the course of this investigation that chloromethyl methyl ether reacts essentially instantaneously with sodium methoxide, the first step must be the slow, rate determining step. The reaction was followed through the rate of disappearance of sodium methoxide by quenching the reaction mixture in excess standard hydrochloric acid and titrating the excess with standard sodium hydroxide. For both methods the experimental technique was the same. For runs at the higher temperatures sealed tubes were used. Those at lower temperatures were run in one hundred milliliter volumetric flasks and aliquots taken at appropriate time intervals. Those organic compounds containing iodine and another halogen were found to be light sensitive and made it necessary to run the sealed tube experiments in the dark and the others in low-actinic glassware. The results are tabulated in the following tables. xii Table 1. Alkyl Bromide Plus. Iodide Ion Alkyl k x 105 1 mole -1 sec -1 4Ha ASa Group 20.3 °C. 50°C. Kcal e.u. CH3cH2 123.1 + 12.3** 1748 + 69 15.6 -18.4 cH2F 55.58 + 4.55 1350 + 18 19.4 -7.3 CH2C1 7.212 + .247 220.7 + 2.4 20.8 -6.4 CH2Br* 2.073 + .060 69.08 + .92 21.4 -6.9 C1121 5.66 + .57** u6 18.5 -14.9 CH Too fast to measure with any accuracy even at 0 3 °C. The specific rate constant is of the order of 0.03 1 mole -1 sec -1 . * Rate constants contain a statistical factor of one-half. ** Deviation estimated for this value, all others are average deviations. Table 2. Alkyl Iodide Plus Methoxide Ion Alkyl k x 105 1 mole -1 min-1 AHa ASa Group °C. 50°C. 20.3 Kcal e.u. CH3 15.01 + .39 433.0 + 8.7 20.5 -6.2 CH2C1 .0863 + .0038 4.417 + .167 22.3 -9.7 CH2Br .031 + .003** 1.023 + .027 21.3 -15.7 CH2I* .01225 + .0012** .536 + .007 23.0 -11.5 * Rate constants contain a statistical factor of one-half. ** Deviation estimated for this value, all others are average deviations. xiv Table 3. Alkyl Bromide Plus Methoxide Ion Alkyl k x 105 1 mole -1 min-1 AHa 41Sa Group °C. 50°C. 20.3 Kcal e.u. CH3 17.07 + .58 479 + 24 20.3 -6.6 CH2F 7.613 + .170 218.5 + 9.7 20.5 -7.4 CH3CH2 1.33 + .02 47.2 + 1.6 22.8 -3.2 CH2C1 .0413 + .0010 2.355 + .022 24.7 -3.4 CH2Br* .00613 + .0002 .3703 + .017 25.1 -5.9 * Rate constants contain a statistical factor of one-half.