A. Molinari et al.
catalyzed Kolbe–Schmidt reaction, starting from p-ami-
nophenol or p-acetaminophenol. A gas phase catalytic car-
boxylation reaction in the presence of a basic compound
under conditions of high temperature (493 K) and pres-
sure (0.5–5.0 MPa) has been recently patented [2]. Other
proposed pathways include electrochemical reduction of
an azo compound obtained from the reaction between
salicylic and sulphanilic acid [4, 5]. However, all of the
above processes suꢂer from certain limitations, including
high energy consumption, long reaction times, low yields,
complicated operation and pollution-causing tendencies.
Therefore, they haven’t been implemented so far. Catalytic
hydrogenation represents an important improvement, but
2 Experimental
2.1 Materials
TiO P25 (Evonik) employed throughout this work is a com-
2
mercial photocatalyst. Solvents, such as acetonitrile (CH CN)
3
and 2-propanol (2-PrOH), were purchased from Sigma and
used without further treatments. 5-nitrosalicylic acid is com-
mercial from Fluka. Ethyl 5-nitrosalicylate and ethyl 5-ami-
nosalicylate are synthesized as described in the following.
2.2 Methods
conventional systems require high H pressure (> 5 bar),
2
high reaction temperature (> 373 K), noble metal catalyst.
Moreover, the shown chemoselectivity is usually poor.
It is well known that heterogeneous photocatalysis often
oꢂers an alternative green route for replacing hazardous
processes with pathways of low environmental impact and
allows the synthesis of valuable compounds by shorter
reaction sequences than conventional routes [6–8]. On this
account, and in view of the above mentioned drawbacks
concerning mesalazine synthesis, we are interested here in
demonstrating the feasibility of a mild method of synthe-
sizing 5-aminosalicylic acid that does not need the pres-
ence of any metal. Our project stems from the possibility
of reducing nitroaromatic compounds to the correspond-
Mass spectra were recorded using a LCQ Duo (Thermo-
Quest, San Jose, CA, USA), equipped with an electrospray
ionization (ESI) source. Irradiation was carried out by
using a Helios Italquartz Q400 medium pressure mercury
lamp (400 W) selecting wavelengths higher than 360 nm
2
with a cut oꢂ ꢃlter (15 mW/cm
)
. The incident ꢁux was
1
6
−1
−2
2
.75 × 10 photons s cm , calculated from the meas-
−
2
ured radiant power density in mW cm [20]. UV–vis spec-
1
tra were recorded by a spectrophotometer Jasco V-630. H
NMR spectrum was recorded on 400 MHz spectrometer at
room temperature. Chemical shifts are given in parts per
million (ppm); J values are given in hertz (Hz). Infrared
spectra were obtained with a Nicolet 510P FTIR instru-
ment in KBr, ꢃtted with a Spectra-Tech collector diꢂuse
ing anilines by photoexcited TiO . It has been reported in
2
−
1
literature that this transformation can be accomplished in
organic media by the UV excitation of the semiconducting
oxide dispersed in the reaction mixture containing an alco-
hol as sacriꢃcial reducing agent for photogenerated holes
reꢁectance accessory (range 4000 to 200 cm ).
2.3 Synthesis of Ethyl 5‑Nitrosalicylate
[
6–12]. The additional presence of a sulfonic acid group
allows to perform the reaction in an aqueous environment
with low pH, using formic acid as holes scavenger [13].
When other reducible functionalities are present in the
nitroaromatic compound [14, 15], chemoselectivity can
be reached by a controlled tailoring of the energetics of
TiO [12, 13, 16–19]. Among all the investigated nitroaro-
2
matic compounds, results about photocatalytic reduction
of 5-nitrosalicylic acid have never been reported in the
literature.
Synthesis of compound (2) is mandatory because of the
strong adsorption of (1) on TiO surface as explained
2
below in Sect. 3. For the preparation of ethyl 5-nitros-
Herein, for the ꢃrst time we report that photoexcited
alicylate (2), concentrated H SO (0.5 mL) is added to
2
4
TiO dispersed in a de-aerated reaction mixture made of an
2
a solution of (1) (1.5 g, 8.2 mmol) dissolved in absolute
organic solvent and 2-propanol as sacriꢃcial reagent cata-
lyzes the quick and selective reduction of 5-nitrosalicylic
acid methyl ester to the corresponding aniline. The product
obtained by the photocatalytic process has been compared
with that prepared by conventional synthesis and fully char-
ethanol (20 mL) and the reaction mixture is reꢁuxed for
2
4 h. The mixture is then cooled to ambient temperature
and a solid is recovered by ꢃltration and washed (3× 2 mL
cold ethanol). The amount of (2) obtained is 1.34 g (83%
1
1
yield). H-NMR (400 MHz, CDCl ) δ: 11.57 (s, 1H),
3
acterized by ESI–MS and H NMR. Eꢂect of the presence of
8
7
.79 (d, J = 2.8 Hz, 1H), 8.32 (dd, J = 9.2, 2.8 Hz, 1H),
O is also reported. The selectivity is maintained also when
2
.08 (d, J = 9.2 Hz, 1H), 4.48 (q, J = 7.1 Hz, 2H), 1.47 (t,
the starting concentration of nitro compound is increased up
J=7.1 Hz, 3H). See Supplementary Information (Fig. 1S).
to two orders of magnitude.
1
3