4
L. Fedenok et al. / Tetrahedron xxx (2017) 1e7
3. The presence of a carbonyl group in the peri-position with
respect to the alkynyl substituent is essential: this carbonyl
group forms a hydrogen bond with a water molecule thus
simplifying protonation of the a-carbon atom of the triple bond.
This effect may be considered as anchimeric assistance of the
carbonyl group to cyclization.
Scheme 7. The sequence of reactions involved in the reduction of alkynylan-
thraquinones under the action of sodium sulfide.
4
. The ability of sulfur to disproportionate rather easily, with
cleavage of the SeS bond and with charge separation, is a
2
9,30
favorable factor.
sulfide proceeds slowly was confirmed in additional experiments
on the reduction of unsubstituted anthraquinone 17 by sodium
The released atomic sulfur S forms dimers and enters rapid in-
teractions with Na S, which is present in the reaction mixture in
excess; thus S is again generated (Scheme 9), which initiates the
sulfide under the conditions of cyclization. It was demonstrated
2
ꢁ
that even heating of a mixture of 17 and Na
2
S in ethanol at 78 С
2
under argon for 2 h leads only to ~10% formation of anthrahy-
droquinone 18. So, the formation of S occurs slowly, but, in our
next sequence of transformations of the substrate into thienoan-
thraquinone according to Scheme 8.
2
opinion, it is this species that initiates cyclization itself. The
mechanism of cyclization of 1-alkynylanthraquinones 1 under the
action of sulfur is shown in Scheme 8.
Thus, cyclization acquires the features of a chain reaction.
Indeed, the reduction of 1 by sodium sulfide (Scheme 7) is a slow
process, but it triggers cyclization. This determines the existence of
some induction period within the first minutes of the reaction. As
mentioned above, intense precipitation of reaction product 2a is
observed only after 10 min.
The S
shell. The presence of unshared electron pairs allows it to attack the
electron-deficient -atom of the triple bond of the substrate,
2
molecule has a voluminous, readily polarizable electron
b
independently of the state of its valence electrons. The participa-
tion of a water molecule supplying a proton, enhances the inter-
action of the substrate with the sulfur molecule and leads to the
formation of cation intermediate I. The formation of the thiophene
ring takes place in this intermediate. Positively charged alpha-
sulfur atom interacts with the neighboring aromatic carbon atom
and replaces H in the form of a proton. Synchronously, the transfer
The new model of cyclization mechanism allows us to explain
the great difference in reaction times for the cyclization of the two
isomers 1a and 9. Two factors are responsible:
1. The difference in the reactivities of these isomers in this reac-
tion. The low reactivity of 2-phenylethynylanthraquinone 9 is
due to the absence of the possibility of anchimeric assistance of
of an electron pair along the
s
-bond eS÷S to the
b
-sulfur atom
the carbonyl group in the protonation of the
the triple bond in the substrate (Scheme 8).
a-carbon atom of
(
disproportionation) occurs. As a result of this synchronous elec-
tron transfer, the formation of the thiophene ring and the release of
water and atomic sulfur S take place. The major factors promoting
this cyclization mechanism are listed below:
2. Different steady concentrations of S
reversibility of reaction (2) in Schemes 7 and 9 causes a sub-
stantial decrease in the concentration of S in solution. In the
2
during the reaction. The
2
case of substrate 1a, the reduced form of which participates in
the side reaction of cyclization (Scheme 4), equilibrium (2) is
shifted to the right, which causes a substantial increase in the
1
. Initial components participating in the cyclization, and the final
components of this process are neutral compounds. The cation
2
intermediate I and the transient state TS have an ionic nature.
2
concentration of S in the reaction medium. As a result, the time
The polar solvent (ethanol) stabilizing the transient state causes
a substantial decrease in the energy barrier of cyclization within
this model.
taken for substrate 1a to cylise is incommensurably shorter than
the time of cyclization for its isomer 9.
2
. There is a gain in resonance energy in the formation of the ar-
omatic thiophene heterocycle in the final product of the
reaction.
Comparison of these factors allows one to reveal the principal
difference between cyclization reactions for 1a and 9. Lower reac-
tivity of 9 determines the low rate of S formation (Scheme 8). For
2
this reason, the contributions into the generation of S according to
Schemes 7 and 9 become comparable. This means that cyclization
of 9 does not have a chain nature. It should be added that the long
time for the reaction of 9 increases the probability of its partici-
pation in side processes. The latter processes include, for example,
the formation of 2-(2-anthraquinonyl)-1-phenylvinylsulfide anion
1
9 (Scheme 10).
Being unable to undergo cyclization, it interacts with zero-
valent sulfur or with Na and is oxidized to form disulfide 20,
which gets stabilized with the elimination of S , forming a stable
2 2
S
2
expanded conjugated system of the corresponding butadiene 11. It
should be noted that 1,4-bis(1-anthraquinonyl)-2,3-di(Ph)
Scheme 8. Hypothetical scheme of the mechanism of СН-cyclization of 1-
alkynylanthraquinones initiated by S
Scheme 9. A sequence of the transformations of atomic sulfur formed in situ during
the cyclization of 1-alkynylanthraquinones under the action of S .
2
2
.
Please cite this article in press as: Fedenok L, et al., Mechanism of С-Н cyclization of alkynylanthraquinones into thienoanthraquinones with the