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Long-Range Substituent Effects in Acylation of Thiophene-Pyridine Combinations.

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mechanism[3'. this mechanism is also probable for the
above cleavages''!
Hetarene combinations that can be cleaved by hydrolysis
will in general presumably be obtained if the azoles are
linked, as in ( l o ) , by a C-N bond to a strongly electrophilic hetarene.
151 Yields obtained: ( 5 ) . Y = CH, Z = N , 83%,: ( 5 J . Y = N. Z = CH.
60%; (S),Y = 2 = N, 61% (recorded m.p.'s confirmed).
[6] H . Bredereck, F. Effenberger, and M. Hajek. Chem. Ber. 98, 3178
[7] We are studying the mechanism
[ S ] Th Kauffmann and A . Woltermann, unpublished work.
Long-Range Substituent Effects in Acylation
of Thiophene-Pyridine Combinations
By Tnomas Kauffmann, Alfred Mitschker, and
Hans-Joackim Streitberger"'
That n-butyllithium neither adds to the diarenes ( 5 ) nor
cleaves them may well be due to the relatively high acidity
of ( 5 ) . This was indicated by transmetalation of (S), Y = N,
Z = CH, which occurs almost quantitatively within a few
minutes in ether at 20°C.
As a result of the mesomerism shown in the formula
scheme the nucleophilicity of the terminal thiophene
nucleus in the arene combinations ( I ) to (4)['' would be
expected to be lower than that of thiophene, and this has
been confirmed by the results of acylation experiments.
When acylation in fact occurs-as expected, it takes place
always in the a-position of the terminal thiophene ring
-the yields (Table 1) are always distinctly lower than for
unsubstituted thiophene.
In our experience it is generally difficult to prepare oligoarenes containing more than four hetarene nuclei by means of
organo-lithium and -copper compounds. It is therefore
valuable that the autoclave reaction used for preparation
of the di- and tri-arenes can also be applied to chain extension of tetraarenes ( 11 ) .
1.) n-BuLi (TIIF -60
2.) C u C l 2 ( - 6 0
0 0 0
... + 6 5 @ C ) [8]
i m i d a z o l e , 19flOC
(I), n
= 0, X = H
Whereas there was no acylation of ( I ) or ( 3 ) by 1 mol each
of acylating agent and Lewis acid (SnCI, or TiC1,) under
conditions that led to almost quantitative reaction of
thiophene, it does result with the chloro derivatives ( 2 )
and ( 4 ) (Table 1). Further, with two mol each of acylating
agent and Lewis acid results were, with one exception
[benzoylation of ( 4 ) ] , better than for the non-chlorinated
arene combinations (Table 1). In none of these cases was
there any reaction other than monoacyiation.
Received: July 5 , 1972 [Z 677c I€]
German version: Angew. Chem 84,828 (1972)
We interpret the easier electrophilic substitution at the
cc-position of the terminal thiophene nucleus due to a
chlorine atom in the a-position of the pyridine nucleus
in the following way : An electrophile (R-CO-CI,
R Z O ' , or MCl,) present in the reaction mixture attacks
primarily the pyridine nitrogen atom of the arene
combinations ( I ) and (3). Owing to the mesomerism (6)
the positive charge thus induced in the aromatic system
then makes it more difficult for electrophilic attack to
occur on the terminal thiophene n ~ c l e u s l However,
the chloro compounds (2) and ( 4 ) the electron density on
[l] Protophanes and Polyarenes, Part 9.-Part 8: [2].
[2] Th. Kauffmann. J . Jackisch, A . Wolrermann, and P . Rowemeier.
Angew. Chem. 84. 826 (1972); Angew. Chem. internat Edit. 11, 844
[3] H . A . Staab, Angew. Chem. 74,407 (1962); Angew. Chem. internat.
Edit. I . 351 (1962)
[4] M. A . Khan and J . B. Po/ya. J. Chem. Soc C 1970,85.
[*] Prof. Dr. Th. Kauffmann, Dip1.-Chem. A. Mitschker, and
DipLChem. H.-J. Streitberger
Organisch-Chemisches lnstitut der Universitat
44 Munster, Orleans-Ring 23 (Germany)
[**I This work was supported by the Deutsche Forschungsgemeinschaft.
the Landesamt fur Forschung des Landes Nordrhein-Westfalen, and
the Fonds der Chemischen Industrie.
The structural formulas above are in accord with analytical
values and spectra (MS, NMR, IR).
Angew. Chem. internat. Edil. / Vol. I 1 11972) / N o . 9
Table 1. Acylation of thiophene and thiophene-pyridine combinations with 1 mol each of acylating agent and
Lewis acid (in parentheses: with 2 mol each).
3 h in benzene,
( 5 h in benzene,
8O'C) [a]
x = C1
0 (O)%
16 (45%
0 (6OY%,
35 (771%
0 (21)"A
18 (48)%
< 1 (68)""
96 (981%
5 h in benzene,
Yields and rn p's of the products
(S), n = 0
(5), n =1
x = c1
24 (62)"$
98 (98)%
[a] Conditions for reaction with two mol each of acylating agent and catalyst
the pyridine nitrogen is decreased by the -I effect of the
chlorine to such an extent that electrophiles no longer
add so readily to the pyridine nitrogen; and additionally
the chlorine atom exerts steric hindrance.
Triarenes of the Type Nucleophile-ElectrophileNucleophile Containing Pyrimidine or s-Triazine as
Central Nuc]eus[llf**]
By Thomas Kauffinann, Patricia Bandi, Wolfgang Brinkwerth, and Bernhard Greving[*]
Systems Nu-El-Nu
composed of nucleophilic (Nu) and
electrophilic (El) groups of the 2[p/n]-electron level[" are
important in organic chemistry both for syntheses
H ,N-CO-NH,,
and as linking member between carbon chains (low- and high-molecular carbonic acid esters
and urethanes). On the basis of the arenology principle
(cf. 12)) we are interested in systems Nu-El-Nu
of the
6x-electron level. In particular, we envisage them as useful
units in polyarene syntheses.
This interpretation is supported by the fact that on
titration in acetic anhydride with 0.1 N perchloric acid
(added in glacial acetic acid) the chlorinated compounds
(2) and ( 4 ) proved clearly less basic['] than (1) and ( 3 )
and, correspondingly, unlike ( I ) and ( 3 ) , d o not form
picrates with ethanolic picric acid.
It is to be expected that such substituent effects will often
play a role in reactions of substituted polyarenes consisting
of nucleophilic and electrophilic hetarenes and will also
be effective, though to a smaller degree, over more than
three nuclei.
Received: July 5, 1972 [Z 677d IE]
German version: Angew. Chem. 84,829 (1972)
[l] Protophanes and Polyarenes, Part 10.-Part 9 : Th. Kuuffmann,
J . Legler, E. Ludorff, and H . Fischer. Angew. Chem. 84, 828 (1972);
Angew. Chem. internat. Edit. 11,846 (1972).
[2] The new arene combinations / 3 ) (m.p. 118-120°C; 49%) and 14)
(m.p. 121 "C, 44%) were prepared, analogously to the lower homologs
( I ) and (2) [3], by treatment of 5-lithio-2,2'-bithiophene with, respectively, 2-fluoropyridine at 1OO'C in di-n-butyl ether/hexane (2 : 1 )
and 2,6-dichIoropyridine at 45OC in etherihexane (1 : 1).
[3] Th. Kuuffmann, E. Wienhojer, and A . Woltermann, Angew. Chem.
83, 796 (1971); Angew. Chem. internat. Edit. 10, 741 (1971).
r4] It is known that, analogously, electrophilic attack at the P-position
of the pyridine is made much harder by formation of an electrophile/
pyridine adduct 1 7 ) . H . C. Brown and B. Kunner, J. Amer. Chem.
SOC. 75, 3865 (1953); H . C . can der Plus and H . J . Den Hertog, Tetrahedron Lett. 1960, 13.
[5] Basicity constants (pK,): pyridine 8.7; 2-chloropyridine 13.3;
( 1 ) 10.3; (2) 14.9; ( 3 ) 10.5; (4) 15.4. These values were obtained
by potentiometric measurements in acetic anhydride/glacial acetic
acid with a glass electrode and extrapolation to an aqueous medium
a s described by C . A . Streuh. Analytic. Chem. 30, 997 (1958).
As first representative we were able to prepare 2,6-di-(2thienyl)pyridine, but only in 18% yield in spite of systematic
experiments[31.The electrophilic activity of the pyridine
nucleus of 2-chloro-6-(2-thienyl)pyridine, weakened by
internuclear electron exchange, obviously does not suffice
for smooth reaction with 2-lithiothiophene. More strongly
electrophilic nuclei should thus be more suitable as central
nucleus, and this has been confirmed.
By starting from the diarenes ( I ) , which are accessible
from pyrimidine and 2-lithio-thiophene, -1 -methylpyrrole
[ ( l )X
, = NCH, ;m. p. 7 6 7 5 "C], or -furan in 46,35, and
53% yield[4,51, respectively, the pale yellow triarenes
(2a)--(2j) (Table 1 ) could be obtained, in some cases in
satisfactory yield, by the action of a molar amount of each
lithium compound (in ether at - 30"C)r61.
(I), X
= S [41
X = NCH, [5]
0 [4J
1. l i Q
2. KMnOa
[*] Prof. Dr. Th. Kauffmann, P. Bandi, DipLChem. W. Brinkwerth,
and B. Greving
Organisch-Chemisches Institut der Universitat
44 Miinster, Orleans-Ring 23 (Germany)
[**I This work was supported by the Deutsche Forschungsgemeinschaft,
the Landesamt fur Forschung des Landes Nordrhein-Westfalen, and
the Fonds der Chemischen Industrie.
A n g e w Chem. internat. Edit. / Voi. I I (1972) / No. 9
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pyridin, acylation, effect, thiophene, long, substituents, ranger, combinations
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