THIOPHENE AND DERIVATIVES€¦ · The synthetic uses of thiophene derivat- ives for the synthesis of aliphatic compounds by desulfurization follow. Two ... thiophenes. In the last

THIOPHENE AND ITS DERIVATIVES

Part Four

Edited by

Salo Gronowitz University of Lund

Lund, Sweden

WILEY

AN INTERSCIENCE" PUBLICATION

JOHN WILEY & SONS

NEW YORK CHICHESTER BRISBANE TORONTO SINGAPORE

This Page Intentionally Left Blank


Part Four

This is a part of thefbrty-fourth aolume in the series

THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS


A SERIES OF MONOGRAPHS

EDWARD C. TAYLOR, Editor

ARNOLD WEISSBERGER, Founding Editor


Part Four

Edited by

Salo Gronowitz University of Lund

Lund, Sweden

WILEY

AN INTERSCIENCE" PUBLICATION

JOHN WILEY & SONS

NEW YORK CHICHESTER BRISBANE TORONTO SINGAPORE

In recognition of the importance of preserving what has been written, it is a policy of John Wiley & Sons, Inc. to have books of enduring value published in the United States printed on acid-free paper. and we exert our best efforts to that end.

Copyright :c) 1991 by John Wiley & Sons, Inc.

All rights reserved. Published simultaneously in Canada

Reproduction or translation of any part of this work beyond that permitted by Section 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & Sons, Inc.

Library of Congress Cataloging in Publication Data:

Thiophene and its derivatives.

(The Chemistry of heterocyclic compounds, 0069-31 5 4 v. 44) "An Interscience publication." Includes bibliographies and indexes. 1 . Thiophene. 1. Gronowitz. Salo. 11. Series.

QD403.T55 1985 547'.594 84- I5356 ISBN 0-471-61221-9 (pt. 4)

1 0 9 8 7 6 5 4 3 2 1

Contributors

Giovanni Consiglio, Dipurtimento di Chimica Oryunicu, Bolognu, Ituly

Carlo Dell’Erba, Istituto di Chimica Organica, Genova, Italy

Salo Gronowitz, Division of Oryanic Chemistry I , Chemical Center, Unicersity of Lund. Lund, Sweden

Anna-Britta Hornfeldt, Division of Oryunic Chemistry I , Chemical Center, Uni- wrsity of Lund, Lund, Sweden

Marino Novi, Istituto di Chimica Oryanica, Genooa, Italy

Jeffery B. Press, R. W. Johnson Pharmaceutical Research Institute at Ortho Phurmac*euticul Corporation, Raritan, New Jersey

Domenico Spinelli, Dipartimento di Chimica Organica, Bologna, ItuIy


The Chemistry of Heterocyclic Compounds

Introduction to the Series

The chemistry of heterocyclic compounds constitutes one of the broadest and most complex branches of chemistry. The diversity of synthetic methods utilized in this field, coupled with the immense physiological and industrial significance of heterocycles, combine to make the general heterocyclic arena of central importance to organic chemistry.

The Chemistry of Heterocyclic Compounds, published since 1950 under the initial editorship of Arnold Weissberger, and later, until Dr. Weissberger’s death in 1984, under our joint editorship, has attempted to make the extra ordinarily complex and diverse field of heterocyclic chemistry as organized and readily accessible as possible. Each volume has dealt with syntheses, reactions, properties, structure, physical chemistry and utility of compounds belonging to a specific ring system or class (e.g., pyridines, thiophenes, pyrimidines, three- membered ring systems). This series has become the basic reference collection for information on heterocyclic compounds.

Many broader aspects of heterocyclic chemistry are recognized as disciplines of general significance that impinge on almost all aspects of modern organic and medicinal chemistry, and for this reason we initiated several years ago a parallel series entitled General Heterocyclic Chemistry, which treated such topics as nuclear magnetic resonance, mass spectra, and photochemistry of heterocyclic compounds, the utility of heterocyclic compounds in organic synthesis, and the synthesis of heterocyclic compounds by means of I ,3-dipolar cycloaddition reactions. These volumes werc intcnded to be of intercst to all organic and medicinal chemists, as well as to those whose particular concern is heterocyclic chemistry.

I t has become increasingly clear that this arbitrary distinction created as many problems as it solves, and we have therefore elected to discontinue the more recently initiated series General Heterocyclic Chemistry, and to publish all forthcoming volumes in the general area of heterocyclic chemistry in The Chemistry of Heterocyclic Compounds series.

Deparrmenr 14 Chemisrry Princeton D’niorrsity Princeton, New Jersey

EDWARD C. TAYLOR

vii


In 1952, in the first volume of The Chemistry of Heterocyclic Compounds, Howard D. Hartough described the state of research on the chemistry of thiophene and its derivatives up to 1950. Selenophene and tellurophene were also included in this monograph, which, except for two chapters, was written by Hartough alone. When this book was written, the explosive development triggered by the commercial process for thiophene from butane and sulfur, developed by Socony-Vacuum Oil Company in the 194Os, had just begun. The enormous amount of work carried out on this important aromatic five-membered heterocycle since 1950 makes i t of course impossible for one person to cover all aspects, and an able group of specialists were assembled from all over the world to treat the entire field. This makes some minor overlaps between chapters unavoidable, but I think it is important to treat some topics from different angles of approach.

Because of the wealth of results and the rather large number of contributors, these volumes are not as strictly organized as some previous volumes in this series, but can be considered as a collection of topics on thiophene chemistry. Together, however, it is my hope that these chapters give as comprehensive a description as possible of the chemistry of thiophene and its monocyclic derivatives, based on the literature from 1950 up to the end of the 1980s. References to previous results, treated in Hartough’s book, are also given when necessary.

The chapters fall in two categories: (1) those that treat syntheses, properties, and reactions of thiophenes; and (2) those that systematically treat functionalized simple thiophenes, such as alkylthiophenes, halothiophenes, aminothiophenes, thiophenecarboxylic acids, and so on. The latter chapters, as is custorn- ary in the Taylor-Weissberger series, contain tables of compounds with their physical properties which should be very useful for all synthetic chemists. Part 1 of these volumes contains only chapters in category 1 and starts with a treatise on the preparation of thiophenes by ring-closure reactions and from other ring systems. It is followed by a chapter on theoretical calculations. Then, in two chapters, naturally occurring thiophenes in plants and in petroleum, shale oil, and coals are treated. The topic of the next chapter is the important field of pharmacologically active compounds. The synthetic uses of thiophene derivatives for the synthesis of aliphatic compounds by desulfurization follow. Two chapters treat thiophenes modified at sulfur, namely, thiophene- 1,l -dioxides and thiophene-I-oxides, and S-alkylation of thiophenes. In the last three chapters, the discussion on different reactivities of thiophenes starts with radical reactions of thiophenes, cycloaddition reactions, and photochemical reactions.

ix

X Preface

Part 2 of this five-part volume begins with a treatment of the important field of electrophilic aromatic substitution of thiophenes, followed by systematic treatment of four classes of functionalized thiophenes, namely, the alkyl-, halo-, nitro-, and aminothiophenes.

The first two chapters of Part 3 of this volume treat the chemistry of thiophene derivatives containing thiophene-to-oxygen bonds and thiophene-to- sulfur bonds, respectively, and the remaining chapters cover formyl and acyl derivatives of thiophene, thiophenecarboxylic acids, and thienyl derivatives.

In Part 4, an extensive treatment of physical properties of thiophenes is given. The second chapter deals with the important nucleophilic substitutions of thiophenes, and in the third chapter the many important results in the expand- ing field of biologically active thiophenes, obtained during 1983- 1988, are summarized.

Finally, in Part 5, vinyl thiophenes and thienyl acetylenes will be treated. A second chapter will cover thienyllithium and other organometallic derivatives of thiophene, and in the last chapter, bithienyls will be covered.

I wish to thank all the distinguished scientists who contributed chapters to these volumes for their splendid cooperation, and my secretary Ann Nordlund for her invaluable help. I am also indebted to Dr. Robert E. Carter for correcting my chapters and those of some of the other authors whose native tongue is not English.

SALO GRONOWITZ Lund. Sweden January I990

Contents

1. Physical Properties of Thiophene Derivatives SALO GRONOWITZ and ANNA-BRITI-A H~RNFELDT. . . . . . . . . . . . 1

11. Nucleophilic Substitution of Thiopbene Derivatives DOMENICO SPINELLI, GIOVANNI CONSIGLIO, C A R 1 . O DELL'ERBA. and MARINO N o w . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295

111. Biologically Active Thiophene Derivatives Revisited: 1983- 1988 JEFFFRY B. PRESS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503

xi



Part Four

This is a part of rhejiorry-jourth colitme in the series



CHAPTER I

Physical Properties of Thiophene Derivatives

Salo Gronowitz and Anna-Britta Hornfeldt

Diiision of Organic Chemistry 1 . Chemical Center .

Linit~ersiry u/ Lund. Sweden

I . Thermodynamics and Thermochemistry of Thiophenes . . . . . . . . . . . . . . . . . . I1 . Phase Equilibria. Chemical Equilibria. and Solutions of Thiophenes . . . . . . . . . .

I l l . Dipole Moments and Related Properties of Thiophenes . . . . . . . . . . . . . . . . . 1 . Dipole Moments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 . Various Dielectric Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

IV . General Physical Chemistry of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . V . Electrochemical Properties of Reactions of Thiophenes . . . . . . . . . . . . . . . . . .

3 6 7 7

17 19 20

1 . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2 . Polarography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

A . Halothiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 B . Reduction of Thiuphene Aldehydes and Ketones . . . . . . . . . . . . . . . . . . 23 C . Polarography of Nitrothiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 D . Miscellaneous Polarographic Work . . . . . . . . . . . . . . . . . . . . . . . . . . 26

3 . Anodic Oxidations of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 4 . Conducting Polymers from Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . 29 5 . Cathodic Reduction of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

V1 . Structure Determination of Thiophenes by X-ray Crystallography . . . . . . . . . . . 31 V I I . Surface Chemistry of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

VIII . Gas Chromatography of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 IX . Microwave Spectroscopy of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 X . Electron Diffraction of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

X I . NMR Spectroscopy of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 1 . 'HNMR spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

A . Spectral Interpretation and Special Techniques . . . . . . . . . . . . . . . . . . . 52 B . Coupling Constants of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . 54 C . Chemical Shifts of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 D . 'H NMR Studies of Tautomeric Thiophene Derivatives . . . . . . . . . . . . . . 84

7 l e Chrmisrry n/ Hrrerocyclic Compounds . C'nlume 44: Thiophene and I t s Deriratires. Part Four. Edited by Salo Gronowitz . ISBN 0-471-61221-9 ( ' 1991 John Wiley & Sons. Inc .

1

2 Physical Properties of Thiophene Derivatives

E . 'H NMR Studies of Various Substituted Thiophenes . . . . . . . . . . . . . . . 84 F . 'H NMR Studies of Organometallic Thiophenes . . . . . . . . . . . . . . . . . . 89 G . Miscellaneous ' H NMR Investigations of Thiophenes . . . . . . . . . . . . . . . 89 H . Conformational Studies of Thiophenes by 'H NMR . . . . . . . . . . . . . . . . 91 1 . Dynamic 'H NMR Investigations of Thiophenes . . . . . . . . . . . . . . . . . . 93 J . 'HNMR Spectra of Thiophenes in Nematic Solvents and in Adsorbed States 96

2 . Various Magnetic Investigations on Thiophenes . . . . . . . . . . . . . . . . . . . . 97 98

A . I3C NMR Spectroscopy of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . 98 B . 33S NMR Spectroscopy of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . 107 C . I9FNMR Spectroscopy of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . 108

11 1 a . " B-Substituted Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 b . 27Al-Substituted Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 c . "P-Substituted Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 d . 77Se-Substituted Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 e . ''9Sn-Substituted Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

4 . Nuclear Quadrupole Resonance Spectra (NQR) of Thiophenes . . . . . . . . . . . . 112 A . "CI Spectra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 B . "Br Spectra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

XI1 . Electron Spin Resonance Spectroscopy of Thiophenes . . . . . . . . . . . . . . . . . . 115 1 . Radicals Derived from Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 2 . Radical Anions Derived from Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . 121

A . Carbonyl Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 B . Nitro Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 C . Miscellaneous Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

3 . Radical Cations Derived from Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . 133 4 . Miscellaneous ESR Work on Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . 134

XI11 . Vibrational Spectra of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 1 . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 2 . Vibrational Spectra of Thiophenes and Deuterated Thiophenes . . . . . . . . . . . 136 3 . Vibrational Spectra of Substituted Thiophenes . . . . . . . . . . . . . . . . . . . . . 143 4 . Influence of the Thiophene Ring on the Vibrational Frequencies of Side Chains . 144 5 . Various IR Spectroscopic Investigations . . . . . . . . . . . . . . . . . . . . . . . . . 149

XIV . Electronic Spectra of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 1 . UV Spectra of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 2 . UV Spectra of Charge-Transfer Complexes of Thiophenes . . . . . . . . . . . . . . 162 3 . Fluorescence Spectra of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 4 . Magnetic Circular Dichroism Spectra of Thiophenes . . . . . . . . . . . . . . . . . . 206 5 . Photoelectron Spectra and ESCA Spectra of Thiophenes . . . . . . . . . . . . . . . 207 6 . Miscellaneous Reactions of Thiophenes with Radiation . . . . . . . . . . . . . . . . 209

XV . Mass Spectra of Thiophenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 1 . Fragmentation Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 2 . Appearance and Ionization Potentials of Thiophenes . . . . . . . . . . . . . . . . . 220 3 . Negative Ion Mass Spectra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 4 . Various Mass Spectral Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224

XVI . Optically Active Thiophene Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 1 . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 2 . Optically Active Thienyl and Thenyl-Substituted Acids . . . . . . . . . . . . . . . . 225 3 . Optically Active Thiophenes as Intermediates for Chiral Quaternary Hydro-

carbons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 . . . . . . . . 231

5 . Enzymatic Resolution of Thiophene Derivatives . . . . . . . . . . . . . . . . . . . . 234

3 . 'H NMR Investigations of Other Magnetically Active Nuclei in Thiophenes . . . .

D . NMR Spectra of Thiophenes Bound to Other Magnetically Active Nuclei . . .

4 . Preparation of Optically Active Thiophenes from Chiral Precursors

I. Thermodynamics and Thermochemistry of Thiophenes 3

6. Optically Active Thiophenes by Asymmetric Syntheses . . . . . . . . . . . . . . . . 235 7. ORD and CD Spectra of Thiophenes. . . . . . . . . . . . . . . . . . . . . . . . . . . 236

XVII. Free-Energy Relationships in the Thiophene Series . . . . . . . . . . . . . . . . . . . . 237 1 . Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 2. Thienyl as Substituent on Benzenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 3. Hammett-Type Correlations in Substituted Thiophenes . . . . . . . . . . . . . . . . 238 4. Ortho Correlations in the Thiophene Series. . . . . . . . . . . . . . . . . . . . . . . 241 5. Linear Free-Energy Correlations in Nucleophilic Substitution of Thiophenes . . . 243 6. Various Correlations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 7. Linear Correlations between Physical Properties and Substituent Constants. . . . 245

A. IR Stretching Frequencies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 8. NMR Chemical Shifts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 C. Various Correlations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

I. THERMODYNAMICS AND THERMOCHEMISTRY OF THIOPHENES

Vapor pressures and second virial coefficients for thiophene, 2- and 3- methylthiophene, 2,5-dimethylthiophene, 2-etylthiophene, and 2-chlorothio- phene were measured by an isoteniscopic method in the temperature range 60 100 C.’ The low vapor pressure of thiophene over solid thiophene at - 80’C was measured with a special appara t~s . ’ .~ Vapor pressure-temperature

relationships have been determined for thiophene and 2- and 3-methylthio- ~ h e n e . ~ The vapor pressurc of 2-thiophenecarboxylic acid has been determined by a Knudsen effusion method over the temperature range 41.8-50°C. The lattice energy was 23.17 kcal/mol and the entropy of evaporation 48.71 cal/deg/ moL5 The critical temperature of thiophene has been determined by the sealed- tube method to be 579.4 K.6 Measurements have been reported on the inter- diffusion coefficients of thiophene in binary systems with hydrogen, nitrogen, and oxygen. Collision diameters were evaluated from the viscosity of the vapors.’ The variation of the coefficient of self-diffusion in thiophene with temperature was studied using a spin-echo spectrometer.8

The thermodynamic and thermochemical data of thiophene have been studied in great detail at the Thermodynamics Laboratory of the Bureau of Mines. The heat capacity of thiophene was measured over the temperature range 1 1 340 K. The solid had two A-type transitions at approximately 112 and 138 K, an isothermal transition at 171.6 K, and a short region of anomalously high heat capacity on the high-temperature side of the latter transition. The heat of transition ( 1 52.4 cal/mol), heat of fusion (121 5.5 cal/mol), and the triple point (234.95 K) were obtained. The vapor pressure of thiophene was measured over the tempcrature range &120C, and the following equation was found to fit the data log,,P (mm) = 6.95926-1246.038/(221.354 + t ) . The normal boiling point was determined to be 84.16C. The heat vaporization of thiophene was measured at three different temperatures, and the values found were 8032, 7808, and 7522 calimol at 45.36, 63.08, and 84.16”C, respectively. The heat capacity of


thiophene vapor was measured at five different temperatures in the range 343472 K. The experimental values for Ci, the heat capacity in the ideal-gas state, may be represented by equation Cp = - 7.017 + 0.10045T- 6.325 x 10-'TZ. An equation for the second virial coefficient B in the equation of

state P V = RT + BP, was obtained from thermal data. The equation is B (liters) = - 0.435 0.0172 exp(1200/T). The entropy of liquid thiophene at 298.16 K is

43.30 f O.lOcal/deg/mol. The entropy of the ideal gas at the normal boiling point (357.32 K) and 1 atmosphere pressure is 70.04 + 0.20 cal/deg/m01.~

The heat of combustion of thiophene was determined. For the reaction C,H,S (I) + 13/20, (g ) + 0.7H,O = 4C0, (g) + H2SO4, 1.7H,O at 298.16 K, A H , = - 667.19 kcal/mol. The heat of formation of liquid thiophene is 19.52 kcal/mol, and the heat of formation of the gas is 27.82 kcal/mol, both at 298.16 K.9 Later determinations of the heat of combustion gave - 676.09 kcal/mol" and heat of formation of 19.13 +_ 0.15 kcal/mol,' which

was later corrected to 19.35 & 0.15 kcal/mol at 25°C" and 19.20 k 0.239 kcal/ mol." For some other determination of the heat of combustions, see Refs. 13 and 14.

From the heat combustion and from values of thermochemical bond energies a resonance energy of 20 kcal/mol was calculated for thiophene."

Various thermodynamic properties of 3-methylthiophene in the solid, liquid, and vapor states have been determined between 12 and 473 K. The entropy of the liquid at 298.16 K, 52.18 k 0.10 cal/deg/mol, was calculated from measured values of the heat capacity of the liquid and the heat of fusion (2518 cal/mol) at the triple point, 204.19 & 0.05 K.

Experimental results obtained for the heat capacity of the liquid (Csafd), the heat of vaporization (AH"), the heat capacity in the ideal gaseous state (C;), and the second virial coefficient [B = (PV - R T / P ) ] are represented by the empir- ical equations:

Crafd (hq) = 46.074 - 0.17610T + 6.8006 X W 4 T 2 - 6.8021

x 10-'T3 cal/deg/mol (207-337 K )

A H v = 13.593 - 13.913Tcal/mol(329-389 K)

(1 )

(2)

C ; = - 1.375 + 9.4508 x 10-"T - 4.2587 x lO-"TZ cal/deg/mol(375475 K) (3)

(4)

From determinations of the heat of combustion, the standard heat of formation [AH," (liq)] of 3-methylthiophene from graphite, hydrogen, and rhombic sulfur was found to be 10.49 k 0.20 kcal/mol at 298.16 K. Calorimetic, spectroscopic, and molecular structure data were used to compute the functions ( F O - H g ) / T) , (Ha - HG), S" , and C i at selected temperatures between 0 and IOOOK. The height of the barrier to internal rotation ( - 600 cai/mol) was evaluated from the experimental entropy and vapor heat capacity data. Values of AH,", AF,", and logloKf for the formation of 3-methylthiophene in the ideal-gas state from

B = 75 - 94.56 exp (IOOO/T) ml/mol(329473 K)

I. Thermodynamics and Therrnochemistry of Thiophenes 5

graphite, hydrogen and gaseous diatomic sulfur were computed from the thermodynamic functions and appropriate calorimetric data. '

For 2-methylthiophene, the following thermodynamic data were obtained. Values of the heat capacity for the solid and liquid [Cut,, = 45.85 - 0.1754T+ 6.772 x 10-4T2 - 6.771 x 10-7T3cal/deg/mol(213-344K)], and

the vapor [CP = - 1.745 + 9.562 x I0-'TZ - 4.420 x 10-'T2 cal/deg/mol (375473 K)]; the heat of fusion (2263 cal/mol) at the triple point (209.79 - + 0.05 K), the entropy in the liquid state at 298.16 K (52.22 cal/deg/mol); the

heat of vaporization [AH, = 11651 - 3.937T - 1.364 x lo-' T 2 cal/mol (343-385 K)]: the second virial coefficient in the equation of state P V = RT (1 + B / V ) [ B = 114-127 exp (900/T) ml/mol (343-473 K)]; and the standard heat of formation of the liquid from graphite, hydrogen, and rhombic sulfur [AH;:Z5 = 10.86 5 0.21 kcal/mol]. (10-340 K) were computed and the same chemical thermodynamic properties as for 3-rnethylthiophene were calculated.'

Conjugation energies in thiophene were estimated with the aid of bond energy terms and the calculated heats of formation of thiophene and 2- and 3-methylthiophene compared with the experimental values."

The heat capacities of both the stable crystalline form (T , = 210.55 K, AH,,, = 1958 cal/mol) and a metastable form (TM = 204.87 K, AH,,, = I769 cal/mol) of 2,5-dimethylthiophene were determined by adiabatic calori-

metry. The derived thermodynamic properties of the liquid at 298.15 K are 42.62, 58.49, and 27.91 cal/mol K for the heat capacity (Cp), entropy (So), and Gibbs energy function (- [Go - H;]/T), r e s p ~ c t i v e l y . ' ~ * ~ ~ The detailed trend of the heat capacity in the region of 2-methylthiophene has been delineated from 110 to 195 K by equilibrium adiabatic calorimetry. The temperature dependence is that of a glass-type transition with a continuously inflected curve without a local Enthalpies of combustion for 2-isopropylthiophene have been measured by rotating-bomb combustion calorimetry.22

Tables containing chemical thermodynamic properties of some thiophenes are given in some other report^^^-'^*^^ and tabulated together with those of other sulfur-containing corn pound^.^^-^' Enthalpies of mixing of thiophene and cyclohexane at 45°C have been deterrni~~ed.~' Thermodynamic functions of gaseous thiophene have been calculated from spectroscopic data and molecular structure.j3 Vapor-pressure measurements have been carried out at low temperatures with mixtures of silyl iodide and thiophene, and the stoichio- metry and relative stability of the complex was inferred.34 The saturated vapor pressures of chloro and chlorosilyl derivatives of thiophene have been determined.3 '

The wetting heat of thiophene on silica gel has been determined to 7.93 k 0.03 cal/g by ~ a l o r i m e t r y . ~ ~ The connection between molecular volume and

critical pressure the number of atoms has been studied for th i~phene .~ ' The temperature dependence of the rate of sublimation of thiophene has been in~es t iga t ed .~~ The thermal conductivity of thiophene, which in the solid state undergoes continuous phase transitions, has been measured at 77-300 K.40 The thermochemical behavior of thiophene under high pressure has been ~ t u d i e d . ~ '


11. PHASE EQUILIBRIA, CHEMICAL EQUILIBRIA, AND SOLUTIONS OF THIOPHENES

The liquid-vapor equilibrium of the binary systems e thanol - th i~phene ,“~ .~~ benzene-thiophene,“’. 44-47 methan~l-thiophene,~~.~~ thiophene-fluoroben- ~ e n e , ~ ~ t h i ~ p h e n e - h e p t a n e ~ ~ , ~ ~ , thi~phene-N,N-dimethylformamide,~’ thiophene-l-methylpyrr0lidone,4~ thiophene-nitromethane,”8 and thiophene- methyl ethyl ketone48 have been studied. In most cases these systems were characterized by positive deviations from Raoult’s law. Azeotropes were observed for thiophene-nitr~methane,~~ thiophene-heptane,46 ethanol-thio- phene4’ and methan~l- thiophene.~~ Azeotropic characteristics of aqueous and alcoholic systems composed of alkenes and thiophenes have been ~b ta ined .~ ’ Azeotrope formation between various hydrocarbons and thiophene and 2- and 3-methylthiophene has also been ~bserved . ’~

Several ternary systems have also been investigated. The systems benzene-thiophene-N,N-dimethylformamide and benzene-thiophene-l- methylpyrrolidone were studied under isobaric conditions (760 mm Hg) by the Gillespie method.47 Isobaric studies have also been carried out on the binary system formed by thiophene and benzene with light alcohols.54 A number of ternary systems containing thiophene has been investigated by Francis.55. 56.58-61 Calculation and study of vapor-liquid equilibria5’ in the benzene-thiophene-heptane6’ and ethanol-ben~ene-thiophene~~ ternary systems have been carried out. Phase equilibria for the ternary system n- heptane- thiophene-liquid ammonia have been determined at ternperaturcs of 0 and 20°C. A new method has been proposed that correlates tie-line data in such a manner that a straight line is obtained for most systems, including solutropic systems.64

The relative volatilities of benzene-thiophene6’ and of toluene-methylthiophene mixtures66 in the presence of polar solvents has been investigated. Critical properties and vapor pressure of thiophene have been de te r~n ined .~~

The liquid vapor equilibrium was studied by the distillation of dilute solutions of thiophene in carbon tetrachloride in trichloroethylene and benzene. For highly effective columns ( - I 0 0 theoretical plates) the best testing solution was thiophene in carbon tetrachloride.68 Other workers have suggested the use of dilute solutions of thiophene in benzene as test mixtures in fractional distillation” also (see Ref. 69). The vapor pressure and molar volume of thiophene as a function of temperature have been measured and the cohesion energy dis- c ~ s s e d . ~ ’ The temperature -molar volume relationships for polar solvents and thiophene have been studied.70 Distribution coefficients of dilute solutions of thiophene in trichloroethylene and benzene were determined using 35S and I4C as radioactive indicators. The distribution coefficients were constant and the solutions obeyed Henry’s law.50

A study of the mutual solubility in the binary systems formed by thiophene with aliphatic glycols monoethanolamine and ethylenediamine at 20-80°C

Ill. Dipole Moments and Related Properties of Thiophenes 7

showed that the Van Laar equation can be used for the calculation of the activity coefficient of these system^.^' A comparative study of the solubility of thiophene and benzene in the dimethylsulfoxide-octane system has been under- taken.72 The solubility of some thiophenes in 24 organic solvents was studied by determination of the critical dissolution temperature^.^^ The slightly mutual solubilities in water -benzene and water-thiophene systems at 30°C were investigated by measurements of differential refractive indexes.74 The solubility of hydrogen chloride in thiophene has been mea~ured.~'

Freezing-point depressions have been measured for very dilute solutions of thiophene in benzene. Thiophene was found to pack in the benzene crystals with a small volume defect, as indicated by the collision areas (16.7 x 10- '6cm2 obtained from viscosity of vapors) and parachor (187.4). The slightly larger volume occupied by thiophene (124.5 x cm3) than benzene ( 1 17.75 x cm3) in its own crystal lattice was attributed to differences of crystal s t r ~ c t u r e . ~ ~

Solid-liquid-phase diagrams have been obtained for thiophene-fluorobenzene, giving a molecular compound at composition 1 : Phase equilibria have also been determined for the binary systems of thiophene with benzene,78 m-xylene, ethylbenzene, cyclohexane, pyridine, and d i ~ x a n e . ~ ~ The solid- phase-melt distribution coefficient for a benzene- thiophene mixture in the low thiophene concentration region has been studied." It has been shown that mixed melting-point determinations between isomeric thiophenes are not more unreliable than in other series, as stated previously." The condensed-phase equilibrium for triphenylmethane and thiophene was studied, and a 1 : 1 complex, dissociated at 56 'C, was observed.82 Cryoscopic data have been presented for solutions of thiophene containing 0.5-1 8 mol% of n-, iso-, sec,- and ~ert-butanol."~

In connection with studies on the quasiracemate method, the melting-point diagrams for mixtures of the (+) and ( - ) forms of a-methoxypenylacetic acid, a-methoxy-2-thienylacetic acid, and a-methoxy-3-thienylacetic acid have been determined.84 The formation and crystallization of thiophene as a glass have been studied.85

111. DIPOLE MOMENTS AND RELATED PROPERTIES OF THIOPHENES

1. Dipole Moments

Dipole moments of a large number of relatively simple thiophene derivatives have been measured, especially by Russian and French workers. The dipole moments were used in connection with estimations of electron- distribution and substituent effects in thiophenes, and for confirmation of molecular orbital (MO) calculations. However, their most important use has been in connection


with conformational analysis of carbonyl-substituted thiophenes and bihetero- cyclic derivatives.

Most of the electrical dipole moments were measured in benzene solution by using the well-known Debye refractivity method, and the method of Halverstadt and KumlerS6 was used to calculate the dipole moments. Dielectric constants were usually measured with a heterodyne beat apparatus.

The measured dipole moments of thiophene in different solvents are given in Table 1, and those of substituted derivatives are collected in Tables 1-9. Quite different values have been obtained for the same compound by different groups, which can be due only partly to variations in the method of calculation.

From the microwave spectra of thiophene and 3-methylthiophene, dipole moments of 0.533 k 0.005 D87*88 and It 0.914 D were ~bta ined . '~

With regard to the direction of the dipole moment of thiophene, there has been some confusion, as some textbooks reported that the dipole moment of thiophene, as well as those of furan and pyrrole, is directed from the positive heteroatom toward the C ( 3 t C (4) b ~ n d . ~ ' - ~ * However, Marinog3 and Lien and Kumler9* presented evidence based on reactivity data, theoretical calculation, and dipole moment values of substituted thiophenes, that the dipole moments of both thiophene and furan are directed from the ring (positive pole) to the heteroatom (negative pole). This was confirmed by studying the orientational influence of dipolar solutes on the aromatic solvents benzene and hexa- fluorobenzene as reflected by NMR chemical shiftsg5 The same technique has also been used to show that the negative end of the dipoles of selenophene and tellurophene are directed toward the heteroatom.96

The experimental dipole moments of substituted thiophenes were compared with electric moment values calculated on the basis of vector addition using the group moment values obtained in the corresponding benzene derivatives, and

TABLE I. Dipole Moments (in Debyes) for Thiophene

Solvent Dipole Moment Ref.

Carbon tetrachloride

Benzene

Hexane Gas

Cyclohexane

Carbon disulfide

"

0.562, 0.003 0.63 0.54, 0.02 0.54 0.54, 0.02 0.53 0.52, 0.05 0.523, 0.002 0.54, 0.002 0.58 0.55, 0.04 0.58 0.524, 0.002 0.53 0.552, 0.01

191 200 203 20 1 101 204 205 199 20 1 202 205 204 199 I56 199

TABLE 2. Dipole Moments (in Debyes) for 2-Substituted Thiophenes

I2 R Z Solvent Dipole Moment Ref.

4 Br

C1

1

NO2 CHO

SH

5 Cocl COOH

CH,CI CSNH,

SCHJ CH,

6 COCII,

8 CH,Cr(CO),

Hg-2-thien yl 2-thienyl

Te-2-thienyl

Dioxane Benzene

CC1, Dioxane Benzene Dioxane Benzene

CCI, Dioxane Dioxane Benzene

CCI,

Benzene

CCI, Dioxane Benzene CCI, Benzene Benzene

CCI,

Benzene

Dioxane

Benzene

Dioxane Dtoxane

Benzene

9

1.41, 0.03 1.35, 0.01 1.36 1.34, 0.01 1.33 1.39 1.38, 0.01 1.60, 0.01 1.48, 0.01 0.83, 0.03 1.20. 0.01 1.13 1.08. 0.01 1.12. 0.03 4.22, 0.05 3.60 3.48 3.55 3.55 3.45 I .50

3.79 1.96 1.26, 0.02 1.30, 0.02 1.58 4.23 0.67 1.50

3.31 3.40 3.36, 0.01 3.41. 0.01

3.31 5.98 3.49 3.28 4.00 2.09 1.91

6.23

1.15, 0.05 1.15, 0.02 0.77 0.96, 0.02 0.66, 0.05 1.53

94

I02 191 I98 100 191 94

100 191

101 111 193 98

I94 111 109

115 196 191

98 117 98

109

98 195 191

123 128 I23 1 20 119 196 98

128

197 94

125 94

101 116

TABLE 2. (Continued)

n R2 Solvent Dipole Moment Ref.

9

10

I 1

12

13

14

15

16

COCC-2-t hienyl COCHdH-2-thienyl

COC,H,

COCCC4H, CH==CHCOC(CH,),

C4CH,)3Cr(CO),

CHSHC6H4-2-CI CH=CHC,H4-3-CI CH=CHC6H44CI CHdHC6H4-2-NO2 CH=CHC,H4-3-NOz CH=.CHC,H,-QNO, CH=CHC,H,

COCCC,H CH=CHCOC,H,-CCI COCH=CHC,H,-4-CI CHdHCOC,H4-4-NOz CH==CIfCOC,H,

"

Benzene

n

Dioxane

Benzene

"

Dioxane Benzene

10

1.53 1.82 0.93

3.09

0.81 1.04, 0.01 0.58, 0.04

4.14 4.14 3.37 3.45 6.33 4.33 3.40

1.63 I .73 1.62 3.64 4.32 4.8 1 0.53

4.30 3.3 1 3.1 I 5.03 3.27 3.11 3.43 4.30 3.19 3.44

3.32 3.75 3.39 3.94

3.25 3.50 3.21 3.91 4.64 4.56 5.59

4.64 5.43

1 I6 126 100

112

124 94

101

123

120

128 123 I I9

118

"

123 120

119 120

123 120 .,

111. Dipole Moments and Related Properties of Thiophenes 1 1

TABLE 2. (Conlintred)

n R 2 Solvent Dipole Moment Ref.

17 CH==CHCO-a-naphthyl CH=CHCO-/l-naphthyl COCH=C'H-z-naphthyl COCH==CH-/+naphthyl

3.3 I 3.62 3.20 3.62

19 COCH=CHC, H Benzene 3.67 CH==&'HCOC,H,C6H, 3.33

i21

120

TABLE 3. Dipole Moments (in Debyes) for 3-Substituted Thiophenes

n R' Solvent Dipole Moment Ref

4 Br NO2 SH

5 CHO

CH3

8 CH,Cr(CO), 2-Thienyl 3-Thien yl Te2-3-thienyl

10 C,H5

Benzene

Dioxane Benzene CCI, Benzene

1.13 3.86, 0.04 I .07

2.94

2.76 2.82

0.82

6.24 1.07 0.75 1 . lo 0.8 I 0.49, 0.05 6.35

198 101 100

1 1 1

194 98

"

128 125

I I6

124 101 128

the results obtained were interpreted to indicate a greater importance of conjugation of the substituent with the thiophene than with the benzene

A study of the dipole moments of some 2-thiophene aldehydes over the temperature range 25-1 45°C showed on comparison with calculated data that the 5-bromo-2-thiophene aldehyde, as well as 2-thiophene a1dehyde,'O5* ' 0 6 exist predominantly in the S.0-cis form 1, in contrast to the corresponding furans. In 5-nitro-2-thiophene aldehyde, the two forms, 1 and 2, are almost equally

ring.97-'04

S.O-cir R = H, BI, NO2

i

$0-tram R P H. BI, NO1

I


TABLE 4. Dipole Moments (in Debyes) for 2.3-Disubstituted Thiophens

n R 2 R J Solvcnt Dipole Moment Ref.

4

5

6

I

Br

CHO I CHO CHO

CHO TeCH, COCH, TeCH, 3-N02-2-thienyl CHO CH, CHO CO,CH, COCH, C6H5

C 6 H S

Br

I CHO OH CHO

Benzene

Dioxane Benzene

1.74

3.19 2.61 2.86 3.39 3.31 3.50 2.84 3.06 2.68 5.55, 0.05 4.84 6.43 4.83 5.32 4.73 1.10

0.86

I98

105

112 I l l

1 I6

101 I l l I28 112 128 112 124

TABLE 5. Dipole Moments (in Debyes) for 2,4-Disubstituted Thiophenes

n RZ R* Solvent Dipole Moment Ref.

CHO I Benzene 2.50 2.51

5

2.22 I CHO

6 CHO CHO Dioxane 2.39

9 CH, CH,Cr(CO), Benzene 6.25

11 C6H3 CH3 0.88

16 G H , C6H5 0.89

I05

111

128

I24

probable.'" The position of the conformational equilibria for the 3-formyl group in 2-chloro-34ormyithiophene and 2-chloro-3-formyl derivatives of other heterocycles have been determined by dipole moment measurements."'

2-Acetylthiophene also appears to exist preferentially in the S,O-cis form.'06 This was elucidated from comparison of the dipole moment of 2-acetylthiophene with that of 7-oxo-4,5,6,7-tetrahydro-ben~o[b]thiophene.'~~ From the experimental dipole moments of 2-benzoylthiophene (3.45 D), 2-thiobenzoyl- thiophene (3.14 D), dL(2-thienyl)ketone (3.75 D) and di-(2-thienyl)thioketone (3.75 D), conclusions about their conformation in solution were obtained. It was claimed that while 2-benzoylthiophene exists in the S-cis conformation, the

TABLE 6. Dipole Moments (in Debyes) for 2,5-Disuhstituted Thiophencs

n R' R' Solvent Dipole Moment Ref.

4

5

6

8

9

12

16

17

18

20

Br

c1

CHO

CHO

CHO CHO

COOH

CN CHO

CH 3

5-Br-2-thienyl 2-Hg-5-1-2-thienyl 5-1-2-thienyl

2-thienyl

COCH,

CH,

C(CH 3 13

C,H,

CH-CHCO-1-naphthyl CH=€HCO-/?-naphi hyl COCH=CH-2-napht hyl COCH=CH-/haphthyl

CH;=NC,H4-4-N02 CH=NC,H,-3-N02 CH=NC6H,

CH=NC,H4-3-CH3 CH=NC6H4-4-CH3

Br

CI

Br

c1

1 NO'

CN CHO

CH,

Br I I

I

Benzene

CCI, Benzene CCI, Deca I i ne CCI, Benzene CCI, Benzene Decaline CCI, Dioxanc Bcnzene

Benzene

Dioxane

Benzene

Dioxanc Benzene

"

Dioxane

Benzene

Dioxane Benzene

Benzenc

I .08 1.13, 0.01 1.08, 0.02 1.04, 0.01 1.05, 0.01 3.31, 0.15 3.28 3.24 3.25 3.32 3.30. 0.15 3.56 4.43. 0.01 3.18. 0.02

2.36 4.18 4.19 4.4 I 3.96. 0.01 3.74, 0.01 3.35. 0.01 3.94, 0.01 0.51

1.73. 0.01 3.21, 0.1 1.87. 0.08 0.85, 0.04 1.28. 0.04 1.79. 0.04 4.96

6.39

0.55

0.92

4.96 4.29 4.70 4.65

5.28, 0.06 5.49. 0.06 2.93, 0.03

2.84. 0.03 2.84. 0.03

102 191

107 194 I l l 194 105 107 194 94

113 193 1 1 1

94

99

94 197 94

193

128

100

124

121

193

13

14 Physical Properties of Thiophcne Derivatives

TABLE 7. Dipole Moments (in Debyes) for 3,4-Disubstituted Thiophenes

n R' R* Solvent Dipole Moment Ref.

4 Br Br Benzene 1.59 198

Br 2.86 I12 CHO I 2.84 105

5 CHO

6 CHO CHO 4.37 1 1 1

TeCH, CHO Benzene 3.03 116

16 C,H5 C,H 5 0.93 I24

Dioxane 4.41

TABLE 8. Dipole Moments (in Debyes) for Trisubstituted Thiophenes

n R' R' R4 R 5 Solvent Dipole Moment Ref.

6 CHO I CH, SH

CHO Benzene 3.80 CH, 1.44

7 CHO CHO CHO 3.61 CHO CHO CHO 3.13

10 CH, CH, CH,Cr(CO), 6.54

22 C6H5 C,H5 C b H 5 1.03

105 109

112

128

I24

TABLE 9. Dipole Moments (in Debyes) for Tetrasubstituted Thiophenes

n RZ R 3 R4 R 5 Solvent Dipole Moment Ref.

4 Br Br Br Br Benzene 0.12 198 CI CI CI c1 0.93 99

I 1 CH, CH, CH, CH,Cr(CO), 6.82 I28

0.60 99 I .04 124

28 CbH5 CbH5 C,Hs CeH,

thioanalogue prefers the S-trans conformation. ' 3-Thiophene aldehyde was estimated in this way to be 75% S,O-cis and 25% S,O-rruns."'

In the same way, the preferential conformers of the various diformyl- thiophenes,lo6- ' ' 2,5-diphenyliminomethylthiophene~,~ O6 and iodinated for- my1 thiopheneslo5 were determined.

Dipole moments for hydroxythiophene systems, thiophenethiols, ortho-hydroxythiophene aldehydes, and formylthiophenes have been compared with those of the corresponding selenophene derivatives. The dipole moments were measured in order to obtain information about tautomeric structure and

Documents

THIOPHENE AND DERIVATIVES€¦ · The synthetic uses of thiophene derivat- ives for the synthesis of aliphatic compounds by desulfurization follow. Two ... thiophenes. In the last