(Z)-And (E)-8-Chlorocinnamohydroximoyl Chlorides with Methoxide
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REACTION OF (Z)- AND (E)-8-CHLOROCINNAMOHYDROXIMOYL CHLORIDES WITH METHOXIDE ION A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN THE GRADUATE SCHOOL OF THE TEXAS WOMAN'S UNIVERSITY COLLEGE OF ARTS AND SCIENCES BY JIN LIU, B.S. •· ·--···-DENTON, TEXAS DECEMBER 2008 TEXAS WOMAN'S UNIVERSITY DENTON, TEXAS November 7, 2008 To the Dean of the Graduate School: I am submitting herewith a thesis written by Jin Liu entitled "reaction of (z)- and (e)-B-chlorocinnamohydroximoyl chlorides with methoxide ion." I have examined this thesis for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Master of Science with a major in Chemistry. We have read this thesis and recommend its acceptance: Accepted: Dean of the Graduate School ACKNOWLEDGMENTS I cordially thank everyone who helped, supported and encouraged me during my studies in the Department of Chemistry and Physics at Texas Woman's University. I especially thank Dr James E. Johnson for the opportunity to conduct research in his laboratory. Without his patient help and guidance, it would have been impossible to complete the thesis. It is my honor and privilege to work under his instruction. iii ABSTRACT JIN LIU REACTION OF (Z}- AND (E)-~-CHLOROCINNAMOHYDROXIMOYL CHLORIDES WITH METHOXIDE ION DECEMBER 2008 New a,~-unsaturated hydroximoyl chlorides and hydroximates were synthesized and characterized. 13C NMR, 1H NMR, IR and elemental analysis were determined for each new compound. The kinetics of methoxide ion substitution on (Z)- and (E)- ~ chlorocinnamohydroximoy l chloride were measured. Identification of the products and the measurement of the rate constants helped with an understanding of the mechanisms of these reactions. lV TABLE OF CONTENTS Page ACKNOWLEDGMENTS ....................................................................................... iii ABSTRACT ........................................................................................................... iv LIST OF SCHEMES .............................................................................................. vii LIST OF TABLES ................................................................................................ viii LIST OF FIGURES .................. .. ............................................................. ............... ix Chapter I. INTRODUCTION ................................................... .................. ..... .... I II. RESULTS AND DISCUSSION ............ ........................ .... .. ............................ 6 III. EXPERIMENT ........................................................................................ 19 General Procedures ....................... ... .............................................................. 19 Kinetic Study .... .. .. ................................ .. ............. .. ....... ...... .. ......................... 20 The Kinetic Method ... .... ... ... ..................................................................... 20 Measurement of Correction Factors ... .. ....................................... ... ........... 20 Preparation of Methoxide Ion Solution Used for Kinetics ..... .. ..... .............. 21 Synthesis ... ........ ... ............. .. ............................. .. .................................... .. ..... 22 Synthesis of (E)-B-Chlorocinnamic Acid (4E and 42)... .... ... .. .. ... .. .... ... .. 22 Synthesis of Methyl (E)- B-Chlorocinnamohydroxamate (6E) ................. 23 V Synthesis of (Z)-0-Methylphenylpropiolohydroximoyl Chloride (8) ........ 24 Synthesis of Methyl (Z,E)- B-Chloro-0-Methylcinnamohydroximate (9) ..24 REFERENCES ................................................................................................... .. 26 VI LIST OF SCHEMES Scheme Page 1. Synthesis of 6E and 6Z ................................. ................ .......................... 7 2. Synthesis 7ZE and 7ZZ and reaction of 7ZE and 7ZZ with methoxide ion ......... 8 vii LIST OF TABLES Table Page 1. The pseudo first order rate constants for the reaction of compound 72 with methoxide ion ..................................................................... ................ 11 2. The pseudo first order rate constants for the reaction of compound 7E with n1ethoxide ion .... ................................................................................ 11 3. Data for the plot of the pseudo first order rate constant for 7E vs [OCH 3]2 ....... 12 4. Values of ln([7E]/[7E] 0) and ([9E]/[ I 0]1+ I )tat 1.456M [Na0CH3] ................. 14 VIII LIST OF FIGURES Figure Page 1. Structure of hydroximoyl chloride, hydroximates, and hydroximoyl cyanides .................................................................................................................. 4 2. De localization of the positive charge protonated ...... ................. ...... .. ..... .. ...... 5 3. The plot of the pseudo first order rate constant for 7E vs [OCH 3]2.. .. .. ... .. .. ... 12 4. The plot of the value of ln([7E]tf[7E]o) vs ([9E]il[ 1O]t+ 1)t.. .............................. 14 5. Two examples of anti vs syn elimination in haloethenes ................................ 16 6. An example of the anti to syn ratio for elimination in conjugated system ......... 17 7. The mechanisms of elimination in chloromaleate and chlorofumarate ...... ....... 18 ix CHAPTER I INTRODUCTION Nucleophilic subsitutions at the carbon-oxygen double bond is one of the most important reactions in synthetic organic chemistry. The mechanism of these reactions has received considerable attention. An important aspect of any mechanism study is the stereochemistry of the reaction. Since it is not possible to have a subsituent on the oxygen of a carbonyl group it is not possible to study the stereochemistry of these reactions. The stereochemistry and mechanisms of nucleophilic substitution at the carbon 1 2 carbon double bond has also been studied extensively - • The mechanism of nucleophilic substitution at the carbon-nitrogen double bond has not received much attention. The barrier for interconversion of the 'z and E isomers of most imines is too low to allow isolation of the Zand E isomers. It has been found that placing a N-methoxy group on the nitrogen atom of the imine raises the barrier to isomerization of imines so that the Z and E isomers can be easily isolated. This has made it possible to investigate the 3 6 stereochemistry of nucleophilic substitution at the carbon-nitrogen double bond. - 4 5 The mechanism ofhydrolysis • of the Zand E isomers of O methylbenzohydroximoyl chloride (lZa and lEa) has been reported. The reaction of (Z)-4-methoxybenzohydroximoyl bromide was 38 times faster at 80 °C than the hydroximoyl chloride. A Hammett plot for the hydrolysis of hydroximoyl chlorides gave 1 a value of 1.4. The Z isomer hydrolyzes about I 05 times faster that the E isomer at 25 °C. It was concluded that the Z and E isomers undergo hydrolysis by rate-determining ionization to a nitrilium ion CDN# + AN), The faster rate of hydroysis of the Z isomer was attributed to the stereoelectronic effect of the nitrogen lone pair being antiperiplanar to the leaving group in the Z isomer. The mechanism of alkoxide ion substitutions of the Z and E isomers of O methylbenzohydroximoyl chlorides has also been investigated. The reaction of the Z isomer with methoxide ion gives greater than 95% retention of configuration. The reaction with methoxide ion with the E isomer is less stereoselective giving about 77% of the product with retention of configuration. The reactions follow second order kinetics and have approximately the same rate constants. The reaction of methoxide ion with the (Z)-hydroximoyl bromide is only 2. 7 times faster than the (Z)-hydroximoyl chloride. A Hammett correlation for the reaction of the hydroximoyl chlorides gave a value of+ 1.90 with cr. It was concluded that the methoxide substitution was proceeding by rate limiting attack by methoxide ion ion on the hydroximoyl chloride followed by rapid loss of chloride ion (AN# + DN), The stereospecificity of the reaction was interpreted in terms of stereoelectronic control during the loss of chloride ion from the tetrahedral intermediate. The reaction of methoxide ion with hydroximoyl cyanides (lZc and lEc) has also been investigated. 7 The (Z)-hydroximoyl cyanide reacted slowly with methoxide ion to give the product with retention of configuration. The E-hydroximoyl cyanide underwent isomerization to the Z isomer faster than it reacted with methoxide ion. These results are 2 consistent with a change in the rate determining step from nucleophilic attack to loss of cyanide ion (AN# + ~#) One objective of this research was to investigate the reaction of methoxide ion on a unsaturated hydroximoyl chloride that had a leaving group ( chloride ion) on the carbon carbon double bond. This investigation would determine if substitution at the carbon carbon double bond is faster than substitution at the carbon-nitrogen double bond. It is well known that imines undergo acid-catalyzed Z/E isomerization. Johnson and his coworkers have investigated the mechanism of these reactions. 7-s It was determined that the isomerization of the hydroximoyl chlorides (lEa) takes place by nucleophilic catalysis when the isomerization is carried out in H36Cl/dioxane solution. Measurement of the rate of incorporation of radioactive chloride during the isomerization of lEa to lZa demonstrated that the isomerization must take place by nucleophilic