Heterogeneous Catalysis
FULL PAPER
mation. It also minimizes the contact time of the oxidant with the catalyst
thereby enhancing the “peroxide efficiency” and restricting the rapid de-
compostion of the peroxide.
N-oxide were formed, whereas with the open-structure mi-
croporous host, containing the redox-active site in high oxi-
dation (MnIII) state (15–17), 92% selectivity for the desired
isonicotinic acid was maintained. In the case of 3-picoline,
the results were even more pronounced: there was almost a
fivefold decrease in the conversion and virtually no nicotinic
acid was produced.
In summary, we have demonstrated that niacin (Vitamin
B3), quinoline-, pyridazine-, pyrazine-, and other heterocy-
clic carboxylic acids can be produced in a single-step, envi-
ronmentally benign fashion by combining single-site, open-
structure, heterogeneous catalysts with a solid source of
active oxygen, acetyl peroxyborate (APB), in the absence of
an organic solvent. The crystallinity and microporosity of
the MnIII-framework-substituted aluminophosphate catalyst
plays a major role in influencing the shape-selectivity and
regiospecificity of the reaction, when APB is used in combi-
nation with this catalyst. The high activities, selectivities and
the relatively mild conditions employed with this single-site
heterogeneous catalyst, coupled with ease of transport, stor-
age, and stability of the solid oxidant, augurs well for the
future use of APB in conjunction with other single-site cata-
lysts for fine-chemical, pharmaceutical, and agrochemical
applications.
At the end of the reaction, the heating was turned off and the contents
of the reactor were cooled (quenched). A mass-balance calculation was
performed at this stage to check for handling and mass losses. Where ki-
netic and rate effects were studied, a mini-robot liquid sampling valve
was employed to remove small aliquots (0.1 mL) of the sample (aqueous
and organic phases) during the course of the reaction. The products were
analyzed either online [by using a robotically-controlled unit with an
online computer-controlled system which is linked to a gas chromatogra-
phy (GC) and/or liquid chromatography/mass spectrometry (LCMS) ap-
paratus]or offline (with a suitable internal standard) by GC (Varian,
Model 3400 CX) employing a HP-1 capillary column (25 m0.32 mm)
and flame ionisation detector using a variable-ramp-temperature pro-
gram (from 65 to 3008C). The identities of the products were first con-
firmed by using authenticated standards and their individual response
factors were determined from a suitable internal standard (adamantane)
by the calibration method. The overall yields were normalized with re-
spect to the (GC) response factors obtained as above and the conversions
and selectivities were determined by Equations (2) and (3):
ꢀ
ꢁ
ðmol initial substrateÞÀðmol residual substrateÞ
Conv: % ¼
ꢁ 100 ð2Þ
mol initial substrate
ꢂ
ꢃ
mol individual product
mol total products
Sel: % ¼
ꢁ 100
ð3Þ
For the internal standard GC method, the response factor (RF) and
mol% of individual products were calculated from Equations (4) and (5).
Experimental Section
APB was freshly prepared according to US 5462692.[8] Briefly, concen-
trated (24.5%) peracetic acid (40 g) was reacted with of partially dehy-
drated borax (Na2B4O7·xH2O 0<x<1; 20 g) for 3 h at 358C to form a
paste. The resulting paste was washed twice on a suction filter with etha-
nol (50 mL) and subsequently dried for 2.5 h at 508C in a circulating air
drying chamber to yield the white powdered product.
ꢂ
ꢃ ꢂ
ꢃ
mol product
mol standard
area standard
area product
RF ¼
ð4Þ
ꢂ
ꢃ ꢂ
ꢃ
RF ꢁ mol product
area product
area standard
The catalytic reactions were carried out in a stainless-steel catalytic reac-
tor (100 mL, Parr) lined with poly ether ether ketone (PEEK). The sub-
strates (4-picoline, 3-picoline, 4-methylquinoline, 4-methylpyrimidine, 4-
methylpyridazine, and methylpyrazine), a suitable internal standard (ada-
mantane), and the catalyst (MnIIIAlPO-5) were then introduced into the
reactor, which was subsequently sealed. The reactor and the inlet and
outlet ports were purged thrice with dry nitrogen prior to reaction. The
contents were stirred at 1200 rpm and the reactor was heated to the de-
sired temperature under autogeneous pressure (N2).
mol % product ¼
ꢁ 100
ð5Þ
mol sample
The identity of the products was further confirmed by using LCMS (Shi-
madzu LCMS-QP8000), which was again employed either online or off-
line. Hot filtration experiments and inductively coupled plasma (ICP)
measurements of the aqueous and organic mixtures were independently
(and regularly) carried out to rule out the possibility of leaching. In most
cases, the catalysts have been re-used three times without appreciable
loss in catalytic activity or selectivity. Further, experiments analogous
those reported earlier,[12,13] were carried out to rule out the possibility of
leaching, and analysis of the resulting filtrate at the end of reaction by
ICP and AAS revealed only trace amounts (<5 ppb) of dissolved metal
ions (Mn, Cr).
The oxidants used in our experiments one of the following:
1) APB (comprising 3.49 g of solid APB, prepared according to US
5462692,[8] and shown by titration studies to liberate 0.701 g of per-
oxyacetic acid and 0.045 g of hydrogen peroxide immediately upon
dissolution).
2) Peroxyacetic acid (comprising 4.2 g of 25% peroxyacetic acid solu-
tion in acetic acid).
3) Peroxyacetic acid+Neoborꢁ (comprising 4.2 g of 25% peroxyacetic
acid solution in acetic acid+1 g Neoborꢁ +1 g NaOH)
4) Peroxyacetic acid+NaOAc (comprising 4.2 g of 25% peroxyacetic
acid solution in acetic acid+0.934 g sodium acetate trihydrate+1 g
NaOH).
Acknowledgement
We wish to thank Borax Europe Limited (Rio Tinto Minerals) for finan-
cial support.
In each case, the oxidant was dissolved in double-distilled water (20.5 g)
and the resulting solution was fed over the course of the reaction, em-
ploying a syringe pump (Harvard “33”) to the stirred contents of the re-
actor. The slow addition of the oxidant to the catalyst/substrate mixture
improves the overall selectivity and also helps minimize byproduct for-
[2]M. Hatanaka, N. Tanaka (Nissan Chemical Ind. Ltd.), WO 9305022,
1993.
Chem. Eur. J. 2008, 14, 2340 – 2348
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2347