OH=>CN / atom less I2-NH3(H2O)

Abstract: A simple, effective, high-yield procedure for the direct oxidative conversion of alcohols to nitriles, was successfully carried out with molecular iodine in ammonia water.

Key words: molecular iodine, oxidation, alcohol, nitrile, ammonia water

Nitriles are very useful intermediates in synthetic organic chemistry,1 especially for ready conversion to many biologically significant compounds; oxazoles,2a–c thiazoles,2d,e tetrazoles,2f–i triazolo[1,5-c] pyrimidines,2j 1,2-di- arylimidazoles,2k etc. Common and reliable oxidation routes to nitriles are from primary amines3 and aldehydes,4 and dehydration of amides5 and aldoximes.6

Molecular iodine is a mild, cheap and easily available oxidizing reagent, and, moreover, it is useful because of its solid form and is less toxic than molecular bromine or chlorine. Previously, simple and effective conversion of aldehydes to the corresponding nitriles in the presence of molecular iodine in ammonia,7 a-iodonation of ketones using I2/H2O2,8a or NaI/H2O2,8b the oxidation of alcohols to the corresponding esters or ketones using IPy2BF4/I2,9 and oxidation of benzylic alcohols to the corresponding aldehydes using I2/cat. TEMPO10 were reported.

However, to the best of our knowledge, there is only one report for the direct oxidative conversion of alcohols as starting materials to nitriles in a one-pot procedure, using NH4HCO3, (Bu4N)2S2O8, and catalytic amounts of Cu(HCO2)2·Ni(HCO2)2 in aqueous KOH and i-PrOH.11 Thus, there is no challenging study for direct oxidative conversion of alcohols to nitriles using molecular iodine in ammonia water. Here, as a part of our basic study for the synthetic use of molecular iodine for organic synthesis,12 we would like to report a practical and facile method for oxidative conversion of alcohols to the corresponding nitriles directly, using only molecular iodine in ammonia water.

First, 3-phenylpropanol was treated with molecular iodine and ammonia water (ca. 28%) at r.t., 50 °C, and 60 °C to form 3-phenylpropionitrile. The reactivity on the oxidative conversion of 3-phenylpropanol to 3-phenylpropio-

SYNLETT 2005, No. 9, pp 1456–1458 Advanced online publication: 29.04.2005

DOI: 10.1055/s-2005-868511; Art ID: U07905ST © Georg Thieme Verlag Stuttgart · New York

nitrile depends on the molar ratio of molecular iodine, NH3, and reaction temperature as shown in Table 1, and the reaction does not require any organic solvent, such as alcohol or THF. Thus, the optimized amounts of ammonia water and molecular iodine were 45 mmol (about 3 mL) and 3 mmol, respectively, for 1 mmol of primary alcohol. Table 2 shows both electron-deficient and electron-rich benzylic alcohols were oxidized to the corresponding nitriles in high yields (entries 1–8). Other primary aliphatic alcohols including neopentyl-type alcohol (entry 14), and diol (entry 15) were also oxidized within 24 hours, and the corresponding nitriles were obtained in high yields. Generally, benzylic alcohols are smoothly converted to the corresponding nitriles, while other alcohols require longer reaction time than benzylic alcohols. Finally, when the reaction was carried out with 1.36 g (10 mmol) of 3-phenyl- propanol, instead of 1 mmol scale, 3-phenylpropionitrile was obtained again in good yield (entry 10). Thus, the reaction can be carried out for gram-scale preparation of nitriles from alcohols (Scheme 1).

Table 1 Oxidative Conversion of 3-Phenylpropanol to 3-Phenyl- propionitrile with I2/aq NH3

a Yield of recovered starting material in parentheses.

I2, aq. NH3

R CH2OH R CN

Scheme 1 Plausible reaction pathway for nitrile

The present method is a simple and efficient procedure for the direct oxidative conversion of alcohols to nitriles, with molecular iodine in ammonia water. The advantages of the present method are the operational simplicity, elimination of use of complicated reagents and procedure, and generality of the reactions.

Typical Procedure for Oxidative Conversion of Primary Alcohols to Nitriles

To a mixture of 3-phenylpropanol (136.2 mg, 1 mmol) and NH3 water (3 mL, 45 mmol) was added I2 (761 mg, 3 mmol) at r.t. under empty balloon.13 The mixture obtained was stirred at 60 °C. After 24 h at the same temperature, the mixture was quenched with H2O (20 mL) and sat. aq Na2SO3 (3 mL) at 0 °C, and was extracted with

Et2O (3 × 20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide 3-phenylpropionitrile in 91% yield in an almost pure state. If necessary, the product was purified by flash column chromatography on silica gel (hexane–EtOAc = 4:1) to give pure 3-phenylpropionitrile as a colorless oil; bp 80–85 °C/1 mmHg (Kugelrohr), (lit.14 bp 113 °C/9 mmHg). IR (NaCl): 2250 cm–1. 1H NMR (CDCl3): d = 2.62 (2 H, t, J = 7.4 Hz), 2.96 (2 H, t, J = 7.4 Hz), 7.23 (2 H, m), 7.28 (1 H, m), 7.34 (2 H, m). 13C NMR (CDCl3): d = 19.1 (s), 31.3 (s), 119.0 (q), 127.0 (t), 128.1 (t), 128.7 (t), 137.9 (q). HRMS (EI): m/z calcd for C9H9N [M+] = 131.0735; found [M+]: 131.0723.

Acknowledgment

Financial support from Forum on Iodine Utilization is gratefully acknowledged.

References

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(13)CAUTION: It is known that iodine reacts with ammonia water under certain conditions to give a black powder of

nitrogen triiodide monoamine (NI3·NH3). The dry powder explodes readily by mechanical shock, heat or irradiation. Although we did not have any incidents in this study, one should be careful.

(14)Online data from Sigma-Aldrich products; http://www.sigmaaldrich.com/Brands/Aldrich.html