Chemistry of Heterocyclic Compounds. Volume 3. Thiophene and Its Derivatives

540 Pages·11.45 MB·english

by  Hartough H.D.

THIOPHENE
and Its Derivatives
This iJ tk third wlumc publiihd in ihe srriei
THE CHEMISTRY OF HETEROCYCLIC COMPOUNDS
~~ ~~
THE CHEMISTRY OF HETEROCYLIC COMPOUNDS
SERIES OF MONOGRAPHS
A
ARNOLD WEISSBERGER, Consulling Edifor
THIOPHENE
and Its Derivatives
HOWARD D. HARTOUGH
Socony- Vacuum Laboratories
Paulsboro, New Jersey
\I'ith Special Chapters by
P. HOCHGESANG
F.
Sorony-Vacuum Laboratories, Paidsboiv, ;Vew Jerq
and BLICKE
F. F.
Universiy o / .Wchinan, Ann Arbor, llichigan
1952
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Copyright, 1952, Intcrscicncc Publiuhcrs, Inc.
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INTRODUCTION THE SERIES
TO
Chemistry of Heterocyclic
The Compounds
The chemistry of heterocyclic compounds is one of the most complex
branches of organic chemistry. It equally interesting for its theoretical
is
implications, for the diversity its synthetic procedures, and for the
of
physiological and industrial significance of heterocyclic compounds.
A field of such importance and intrinsic difiiculty should be made as
readily accessible possible, and the lack of a modern detailed and
as
comprehensive presentation of heterocyclic chemistry is therefore keenly
felt. It is the intention of the present scrica to this gap by expert
fill
presentations of the various branches of heterocyclic chemistry. The
subdivisions have been designed to cover the field in its entirety
by
monographs which reflect the importance and the interrelations the
of
various compounds, and accommodate the specific interests of the authors.
&#arch Loboratories ARNOLDW EISSBERGER
htman Kadak Company
Rochester, h'cw Tork
Preface
Since thiophene was discovered in 1882 by Victor Meyer its importancc
has increased at an accelerating ratr. hlthough there has not been ii
year from to the present without publications concerning thiophene
1883
or its derivatives, there are three main periods in which the greater pro-
portions of the publications were issued. The first of these was the Victor
Meyer period of to which culminated in Victor Meyer’s book
1883 1888,
Die Thiophengruppe (Braunschweig, The second period, which
1888).
should be classified the Steinkopf period, began in 1918 and continued
as
until 1941. Again the work was summarized in a book by Wilhelm
Steinkopf, Die Chemie des Thiophens (Vcrlag von Theodor Steinkopff,
Dresden, 1941). The present period of accelerated research, initiated
by the commercial availability of thiophene, began in 1945 and promises
to continue into the next decade.
The rapid strides in thiophene chemistry between 1944 and 1950 have
created the need for the present volume. For example, the subject
matter of Chapter one of the longest in the book, is covered in less
IX,
than a page in Die Chemie des Thiophens. I once commented before an
American Chemical Society meeting that thiophene chemistry was
merely in its infancy, since there were still so many problems to be under-
taken and solved before we could know its true character. The remark
came back from the that, while this was probably true, thiophene
floor
chemistry was certainly enjoying a robust and healthy childhood.
The present book was begun in 1947 but so many references appeared
in 1947 and 1948 that it was necessary to rewrite most of the chapters
as many as three times. The text originally included references up to
January 1, 1949. Several hundred references appearing in Chemical
Abstracts between January 1 and October 1, 1949, were inserted into the
completed text but in a number of cases it was not possible to handle these
later references in detail. Since October 1, 1949, about four hundred
additional articles and patents have been published.
The treatise was dcsigncd to cover critically all phases of thiophene
chemistry and to point out wine of the existing problems yet to be solved.
In order to achieve this goal, Dr. F. F. Blicke, Head of the Pharmacy
School, University of Michigan, contributed Chapter I1 on toxicological
and pharmacological properties of thiophene, and Mr. F. Hochgesang
P.
of the Physics Division of the Socony-Vacuum Laboratories reviewed
the spectrochemical and related properties of thiophene. In addition,
vii
viii I’reface
Chapter IV includes a complete summary of the unpublished data
obtained in the Socony-Vacuum Laboratories. These data should be
of particular value to petroleum chemists, as well to organic chemists,
as
in identifying natural-source thiophenes and synthetic thiophenes. The
literature was reviewed with the intention of including every significant
reference and every derivative of thiophene. It will be appreciated
that this is a rather formidable task, and I shall be most grateful to those
users of the book who will bring to my attention deficiencies of which
they become aware.
In addition to the contributions mentioned above, I deeply in-
am
debted to Drs. A. A. O’Kelly and D. Badertscher for their encourage-
E.
ment during the writing period. Meisel and E. Crane
Dr. S. L. Dr. M.
were especially helpful in proofreading the manuscript and in offering
critical comments. Great credit goes to Hawthorne for
Dr. W. P. his
painstaking proofreading and critical review of the contents of this
volume which have immeasurably improved its quality and organization.
Special thanks are due to R. Bulkley, L. A. Hamilton, and
Dr. Dr. Mr.
J. J. Dickert, Jr., who graciously volunteered to help in the tedious task
of checking references.
The writing of this was greatly facilitated by private communica-
book
tions to the author from friends in this country and abroad. Sincere
thanks due Robert Levine of the University of Pittsburgh,
are Dr. Dr.
C. D. Hurd of Northwcstern university, Dr. F. F. Nord of Fordham
University, and many others. Dr. Otto Dann of the University
of
Erlangen, Germany, was instrumental in maintaining contact for thc
author with Stcinkopf and in supplying hioqraphical data about
Dr.
Steinkopf. He also transmitted information concerning
Dr. his own
work in thiophene chemistry. Frederick Challenger of the
Dr. Uni-
versity of England, has been helpful in forwarding copics
Leeds, of
articles submitted for publication in English journals many months
his
prior to their availability in this country.
Originally this volume was to include fused ring systems containing
thiophene rings such as thianaphthene and dibenzothiophene. To
expedite publication of thiophene data, the data on condensed ring
systems containing thiophcnc rings now scheduled for publication in
are
a separate volume by the: present author Dr. L. Meisel which
and S.
should appear in 1952 or 1953.
Hercules Exfierimen! Station H.
D. H.
Wilmington, Delaware
Aupt, 1957
Conten te
Preface .............. ..................... ... vii
.
I General Dimxraon ............................................... 1
. History Thiophene ..................... 1
11II11... NOcocmuernreconlfac teu roef oTfh Tiohpihoepnhee nCeo Cmopmoupnodusn dins .N...a..t..u..r..e... ....................................... ...... 161
Rcactiona Thiophcne Compounds 13
IVV .. C&otlimora tion of Thoifo phcne ..................................... 17
VI Removal of Thiophene a
and Petroleum St& .......... ...................... 19
.
Isomorphism and Physic 23
VII . Odor Thiophcnc and Derivatives. ....................... 26
VIII of Its
.
I1 BidogicaJ and. Pharm. ac.o logica.l. A..c.t.i.v.i.ty.. o.f. .T.h..i.o.p..h.e.n.c.. a.n..d. .I.t.r. D..c. riva-
tiver By E F Blukt 29
Introduction ................................ 29
.
I General Biological Effects.. .................................. 29
.
I1. Antihistamine Compounds ..................... 32
111. Pressor Compounds ........................................ 36
IV . Local Anesthetics ................................... 37
V Hypnotia .............................................. 38
.
Antifebridu and Analgesics ........................... 39
VI .
VII . AntirpaModia ..................................... 40
Anticonvulaants. .......................................... 41
VIII
Germicides ......... ........................ 42
X..
Analogs DDT ..... ........................ 43
X . Miroellanocfo ua Compounds and Their ................. 44
XI Properties
. ....
lU Spthemr and and Homalop 41
Phyucal Propertier of Thiophene Its
.
I Synthesis Thiophene and Homologs ...................... 47
of Its
A. Synthuis of Thiophene and Homologs by Ring Closure
Its of
Hydrocarbons ......................................... 48
1. Socony-Vacuum Thiophene Procas .. ... 55
(a) The Roc= .................... ... 55
(b) Materials .. .................. 55
Flow of
(c) Equipment ....................................... 58
Miscellaneous Methods .... .... .................... 60
. 2
Qmure y-Diketona YDiacids, YKeto Acida ...... 63
. B Ring of or
Physical Properties Thiophene and Homologs ............. 64
I1. of Its
Synthesis and Properties the Hydrothiophenes ................ 73
111 . of
A Thiolena (Dihvdrothiophenes) ............................ 74
ix
X
.
III Synthesis Physical Properties of Thiophene and Its Homolog8
and
(confinurd)
.
B Dihydrothianaphthena ......................... 75
C. Thiolane s ........................................ 76
D . Preparation 3-Thiolenr- and lhiolanecarboxylic Acids ...... 78
of
. Molecular Structure Spect
IV tives. By Frank P . aHnocdh grsang ............ 81
Introduction .................................................... 81
I . Molecular Structure and Related Propertics ......... 82
A . Bond Distances and Angles of Thiophene ........... 82
B .. Dipole Moments and Resonance in Thiophene Nucleus ....... 83
C Miscellaneous Related Propertics .......................... 89
.
Theoretical Considerations from the Vicwpint of Spectroscopy and
I1
Summary of Publihed Spectral Data ........................ 91
A . Electronic Absorption Sprctra ............................. 91
B. Electronic Emission Spectra .......... ..... 94
C. Vibration Spectra ...................................... 95
.
D Thermodynamic Functions from Spectroscopic and Molecular
Structure Data .................................... 97
.
111 Applied Spectroscopy .................................... 99
Introduction .................................. 99
.A . U 1t raviole t .A bsor pion Sp cc t ra ...................... 100
B. Infrared Absorption Spcctra ............................ 106
.
C Mass Spectral Data ................................. 132
.
V Factors Affecting Substitution Reactions in the Thiophene Nucleus ... 143
Introduction .................................. ........ 143
I . Resonance in the 'I'hiophcnc Nucleus ..................... 143
.
11 Directive Influcncc of thc Sulfur ;\torn in hlonosuhstitution Keac-
tions ............................................. 144
111. Dirrctive Influences lypic.al (~rlho-pnra-l)ircctingG ruups on thc
of
Thiophcnr Ni~clr.~.s. .............................. 145
IV. 1)irective Influences of'l'ypiral .We ~n-l)irwtingG ~IJII~..S. ....... 147
.
V Methods of Synthcsis in thr '~lii~~p.Slc~rirmn H~a~srd on 1)irrctive
Influences in the 'Thiophriw Nuclrim ..................... 148
A, . Preparation of 3-Sulxititutrd .I'hiophi~tic.*s. ................ 149
3-Alkylthiophents . ................................... 149
3-Nitrothiophenr ........................................ 150
3-Chlorothiophmc . .................................... 150
3-Broinothiophenr ...................................... 150
3-Iodothiophenc .................................... 151
3,CDiaminothiophenc ................................ 151
3-Thenyl Bromidc and Some of Its Kcactioiis ............. 152
.
B Synthcscs Involving thc 3-hfethylthiopl1cne Nttrlcits . . . . . . 152
C . Synthesis of the Pix Isonirric: hl~thyltliioplictirc.a~I~~s.\ Vcilctls~ ~ 152
5-Methyl-2-thiophenecarboxyli(:A rid (I 1 . . . . . . . . . . . . . . . 153
Grignard Method ........................... 153
XI
.
V ractors Substitution Reactions in the Thiophene
Affecting Nucleus
(cnnlinurd)
hcylation and Oxidation ........ . . . . . .... ...... 154
Direct Sodium Metalation (Grignard ‘Type) ... . . . . . . 154
2-Methyl-Cthiophenrcarboxylic Acid (11) ..... . . . . . . 154
Method of Stcinkopf and Hanske ......... . . . . 154
2-hlethyl-3-thiopheneca~hxylicA cid (111) ...... ........ 154
Method of Strinkopf and Jacob ............. . . 154
3-Methyl-2-thiophenecarboxylicA cid (IV) ..... . . . . . . 154
Grignard Method ...................... 154
4-h4ethyl-2-thiophenecarboxylicA cid (V). . . . . . . . . . . 154
Metalation Method ............... 154
Sodium
Acylation Method . . . . . 155
Method of Steinkopf dnd Jacob . . . . 155
4-Methyl-3-thiophenerarboxylirA c.id I Vl) . . . . . 155
Method of Steinkopf and Hanskc ........ 155
1) . Possible Extensioits of the Bt.otnosiiccinintide Kcartion with
Metliylthiophrnrs ................................... 156
.
Vl Alkylation. Polymerizatioir. Hydrogenation and Miscellaneous Reac-
tions of Thiophene . ..... 159
Introduction ........................................ . . . .. .. 159
I . Introduction of Alkyl Groups ............... 159
. Preparation of Alkenyltliioplienrs. ............... 164
I1I11.. Polymerization of Thiophene and Its Homologs ..... ..... . . 165
1V . Hydrogenation of Thiophcne .................. . 167
V Miscellaneous Chemical Reactions of ‘Thiophenc. . 169
.
VI1 Halothiophenes Haloalkylthiophenes 173
and
I . 2-Fluorothiophene ................ ...... .. . . 173
11. Chlorothiophenes and Haloalkylthiophenes . . ... . 173
.4 . Chlorine Addition Products of Thiophenc ....... ..... ... . 174
.
B Chlorine Substitution Products of Thiophenc .... ... . . 179
1 . 2-Chlorothiophene ..................... . . 181
2 . 3-Chlorothiophenc ....................... . 181
3. 2,5-Dichlorothiophcnc ..................... ... . . 182
4. 2,3Dichlorothiophenc . . . . . . . . . . . . . . . . . . . . .. .. . 182
. 2,4-Dichlorothiophene. .................. . . . .. .. . 183
5
6 . 3,4-Dichlorothiophene. . . . . . . . . . . . . . . . . ...... ... . 183
.
7 2,3,4-l’richlorothiophrnr ................. ...... ... . 184
.
8 ................. ....... .. . 184
. 2,3,5-Trichlorothiophene
9 2,3,4, 5-Tetrachlorothiophene . . . . . . . . . ....... .. . 185
.
C Chlorination Alk.vlthio.phenc s. . . ...... ... . 185
. of .
D Introduction of the Halogrns into ail \lkylthiophrne Side Chain 186
.
E Reactions of Chloro- and Haiomrthylthioptirn~.~. .......... 189
.
Physical Roperties .................................. 191
F
111. The Bromothiophenes. .................................. 199
A . Bromination of Thiophcnr . . . . . . . . . ............ 199