NaY Zeolite: A Useful Catalyst for Nitrile Hydrolysis

The NaY zeolite catalysed hydrolysis of nitriles to primary amides is reported. It is found that aryl nitriles with strong electron-withdrawing substituents and cyanopyridines are readily hydrolysed in the water suspension, while aliphatic nitriles do not react.


Introduction
Zeolites are effective catalysts in organic chemistry and their specificity in gas phase transformations is greatly utilised in industry [1].Alkylation reaction, polymerisation, cyclization [2], photoreduction [3], or preparation of nitroalkenes [4], occur in gas phase or with reactants sorbed within zeolite in inert solvent.Recently, several reports on the use of acidic zeolites (HY) in macrolactonization [5], acetalization [6], acetylation [7] and gem-diacetalization [8], as well as the synthesis and application of the first organic-functionalized zeolite-beta [9], prompted us to investigate the new catalytic possibilities of NaY zeolite.
Here we wish to report the application of NaY zeolite as reusable catalyst in the hydrolysis of nitriles to primary amides.

Results and Discussion
In our experiments the suspension of NaY zeolite and a nitrile in water (or methanol) was heated to reflux for a given period (Table 1), zeolite was filtered off, and products were separated (or directly crystallised).Most important observation is that nitriles are hydrolysed only to the amide stage.Cyanopyridines and benzonitriles with electron-withdrawing substituents are readily hydrolysed in good yield (Table 1, entries 1-3, 7).Benzonitrile (10, entry 6) was totally resistant to hydrolysis, while benzonitriles substituted with week inductive electron-withdrawing groups (with strong +R, 4-aminobenzonitrile (13) and 4-(5cyanopentoxy)benzonitrile (16) [10], Table 1, entries 8 and 10) were hydrolysed, although in low yield (35% and 21%, respectively).Hydroxy substituent completely prevented the hydrolysis (15, Table 1, entry 9) probably as a consequence of phenoxy ion formation.The case of di-nitrile 16 is very inter-esting: it shows that hydrolysis proceeds by blocking the formation of phenoxy ion, while at the same time pointing to the resistance of aliphatic nitriles to hydrolysis.The resistance of aliphatic nitriles was confirmed by attempted hydrolysis of CH 3 CN (not shown) and by hydrolysis of ethyl 3cyanopropanoate 20 only to cyanoacid 21 (Table 1, entry 12).Benzylic cyano group was also found to be resistant to applied conditions (9, Table 1, entry 5), or was very slightly hydrolysed when CH 2 CN was attached to the electron-withdrawing pyridine ring (7 → 8, 16%, Table 1, entry 4).
In some cases, prolonged reaction time resulted in higher yields, as is given for 4-cyanopyridine (1) (Table 1, entry 1, 6 h (67%) → 24 h (87%)).The reusability of NaY catalyst was tested using 3cyanopyridine (3, Table 1, entry 2).Four runs were performed with the same batch of the catalyst without significant loss of its activity.
In Table 2 the influence of reactant (solvent) is shown.Using methanol instead of water the imino ester 22 was obtained in good yield (67%; entry 2), while ethanol and higher homologues (propanol and 1-butanol) were ineffective.However, hydrazine hydrate afforded isoniazide (23, 67%) along with 18% of isonicotinamide (2).The influence of the amount of catalyst on product distribution is exemplified with methanolysis of 4-cyanopyridine (1) (Table 3).Product formation started with 6% (w/w) of catalyst, and the increase of zeolite part did not significantly affect the product distribution, what, beside its already shown reusability, confirms the true catalytic nature of NaY zeolite.

Conclusion
We have shown that NaY zeolite can be used in the simple procedure as a reusable catalyst for hydrolysis of aromatic nitriles, primarily of cyanopyridines and benzonitriles possessing electronwithdrawing groups.Contrary to hydrolysis under acidic conditions, benzyl-and alkanenitriles are stable under conditions applied, so enabling their further selective transformations.In addition, NaY zeolite can also be used for imino ester preparation as an alternative to Pinner synthesis.

General
Melting points were determined on a Mikro-Heiztisch Boetius PHMK apparatus and were not corrected.IR spectra were recorded on Perkin-Elmer spectrophotometer FT-IR 1725X. 1 H and 13 C NMR spectra were recorded on a Varian Gemini-200 or Bruker AM-250 spectrometers.Chemical shifts were expressed as ppm (δ) values and coupling constants (J) in Hz.Mass spectra were taken on a Finnigan-MAT 8230 spectrometer, as indicated below.

Hydrolysis of Nitriles -General
The suspension of a nitrile (200 mg) and zeolite (800 mg) in water (5 ml) was heated to reflux (for details see Table 1).The hot reaction mixture was filtered and zeolite was washed with water (and/or methanol).When catalyst was reused, it was dried on air overnight.Pure amides were crystallised directly from the crude product mixture or were purified by column chromatography (SiO 2 or RP-18).All isolated compounds were fully characterised by spectroscopic and analytical methods.
The data of known compounds were compared with literature data given in [13], and that refers to: 2: mp 152-154 o C, [14]

Iminoester 22
The suspension of 4-cyanopyridine (1, 200 mg) and zeolite (800 mg) in methanol (5 ml) was heated to reflux for 14 h.Hot reaction mixture was filtered and zeolite was washed with methanol.Crude product was chromatographed on Lobar RP-18 column (eluent: CH

Table 1 .
Hydrolysis of nitriles into amides a .
a Yield of isolated compounds.