CL-150134
Received: February 10, 2015 | Accepted: March 9, 2015 | Web Released: March 13, 2015
Synthesis of Common-sized Heterocyclic Compounds by Intramolecular Cyclization
over Halide Cluster Catalysts
Sayoko Nagashima,*1 Tomoaki Sasaki,1 Satoshi Kamiguchi,2 and Teiji Chihara1
1Graduate School of Science and Engineering, Saitama University, Shimo-Okubo, Sakura-ku, Saitama 338-8570
2Organometallic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198
(E-mail: nagasima@apc.saitama-u.ac.jp)
Five- to seven-membered common-sized heterocyclic com-
pounds containing an oxygen, sulfur, or nitrogen were
synthesized by the intramolecular condensation of α,ω-hydroxy,
mercapto, or amino alkanes, respectively, over halide cluster
complexes as a thermally stable molecular solid weak acid
catalyst in the gas phase at temperatures ²150 °C. From ω-
mercapto and ω-amino alcohols, cyclic sulfides and amines were
obtained, respectively. These unimolecular reactions are ther-
modynamically and kinetically favored.
details are summarized in the Supporting Information. When
1,4-butanediol was reacted over niobium cluster [(Nb6Cl12)Cl2-
(H2O)4]¢4H2O (1) at 350 °C, the catalytic activity decreased
with time, while the selectivity was stable from the beginning of
the reaction, as Figure S1 in the Supporting Information shows.
Cyclization yielding tetrahydrofuran proceeded with a selec-
tivity of 99%. Approximately 100 reports of this catalytic
cyclization have been published. This is essentially a dehydra-
tion reaction of two hydroxy groups to yield ether, and hence
acidic compounds including alumina6a and montmorillonite6b
have been reported as the catalysts, while RuH2(PR3)4 (R = Me,
7c
Approximately 50% of all known organic compounds
contain a heterocyclic ring.1 Rings of this type commonly occur
in nature, and many biologically important compounds are
heterocyclic. The synthesis of heterocyclic compounds has a
long and extensive history, but a broadly applicable catalytic
method for the synthesis of commonly occurring heterocyclic
rings containing either O, S, or N has not been developed. We
have studied the use of thermally stable halide cluster catalysts,2
and developed various types of ring-closure condensation
having characteristics exemplified in the one-step synthesis of
indenes from benzaldehyde and methyl ketones at 200-400 °C,3
and 3-methylbenzofuran from phenol and acetone.4 Both these
reactions are possible because of the thermal stability of the
cluster catalysts. Another type of reaction involves intramolec-
ular condensation of 1,2-C6H4(CH2RH)2 (R = O, S, NH) to
yield heterocyclic compounds 1,2-C6H4(CH2RCH2) in a gas-
phase reaction (Scheme 1).5 The two functional groups in these
reactants are constrained by the need for close proximity, which
may not be a requirement for cyclization. We have attempted to
expand the scope of this catalysis using simple α,ω-disubstituted
aliphatic compounds containing hydroxy, mercapto, or amino
groups as reactants (Scheme 2).
Et, Bu),7a copper oxide,7b and Cu/SiO2 have been reported to
catalyze dehydrogenation to yield γ-butyrolactone in a temper-
ature range 205-250 °C.
Figure 1 shows the effect of temperature on the activity and
selectivity for the reaction of 1,4-butanediol over 1. Substantial
catalytic activity occurred at 150 °C. Cyclization to yield
tetrahydrofuran was the main reaction at all temperatures tested.
Formation of intermolecular condensation chain products (e.g.,
5-oxo-1,9-nonanediol) were not detected at any tested temper-
ature. Molybdenum, tantalum, and tungsten halide clusters
catalyzed the cyclization with >86% selectivity, as Table S1 in
the Supporting Information shows.
The results for reactions of various α,ω-disubstituted
alkanes over 1 supported on silica gel (1/SiO2) are shown in
Table 1. The compounds 1,5-pentanediol, 1,6-hexanediol, and
1,4-butanediol, selectively produced their corresponding cyclic
ethers, although the reactivity decreased with increasing alkyl
chain length (Entries 5-7). Fewer reports have involved longer
100
80
60
40
20
0
Halide cluster complexes were synthesized according to
published procedures and used as crushed crystals or as samples
supported on silica gel at 5.0% by weight. The reactions were
performed in a conventional continuous gas-flow microreactor
operated at the atmospheric pressure of helium. Experimental
− H2R
RH
RH
100
200
300
400
500
R
R = O, S, NH
Temperature/°C
Scheme 1.
Figure 1. Effect of temperature on the cyclization of 1,4-butanediol
over [(Nb6Cl12)Cl2(H2O)4]¢4H2O (1). Following the treatment of 1
(10.0 mg) in a helium stream (600 mL h¹1) for 1 h, the reaction
was initiated by introduction of 1,4-butanediol (0.136 mL h¹1, 1.50
mmol h¹1) into the helium stream with no change to the temperature.
Conversion of 1,4-butanediol ( ), selectivity for tetrahydrofuran ( ),
selectivity for 2,5-dihydrofuran ( ) at 6-7 h following initiation of
the reaction.
− H2R′
RH
R
(CH2)n
(CH2)n
R′H
R, R′ = O, S, NH
n = 4 − 6
Scheme 2.
© 2015 The Chemical Society of Japan