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

Abstract: Various primary alcohols, and primary, secondary, and tertiary amines were oxidatively and efficiently converted into the corresponding nitriles in good yields, by 1,3-diiodo-5,5-dimethyl- hydantoin (DIH) in aqueous ammonia (NH3) at 60 °C.

Key words: primary alcohols, primary amines, secondary amines, tertiary amines, 1,3-diiodo-5,5-dimethylhydantoin, nitriles, aqueous ammonia

Nitriles are very useful intermediates in synthetic organic chemistry,1 especially in reactions for ready conversion into many biologically important compounds, such as ox- azoles,2a-c thiazoles,2d,e tetrazoles,2f-i triazolo[1,5-c]pyri- midines,2j and 1,2-diarylimidazoles.2k Typical one-carbon homologated nitriles are obtained by the reaction of alkyl halides with toxic cyanide. On the other hand, dehydration of amides and aldoximes, and oxidation of primary amines provide the corresponding nitriles, keeping the number of carbon atoms constant. Thus, nitriles are generally prepared by the dehydration of amides with SOCl2, TsCl-pyridine, P2O5, POCl3, COCl2, (EtO)3P/I2, and Ph3P/CCl4.3 Nitriles are also prepared by the condensation of carboxylic acids with NH3/silica gel, NH3/ethyl polyphosphate, etc., and by the reaction of esters with Me2AlNH2.3 Oxidative conversion of primary amines into the corresponding nitriles has been also studied well, using AgO,4a Pb(OAc)4,4b-e cobalt peroxide,4f nickel peroxide,4g Na2S2O8 or (Bu4N)2S2O8 with metals,4h-k NaOCl,4l-n K3Fe(CN)6,4o Cu(I) or Cu(II) with oxygen,4p-s RuCl3 and related Ru reagents,4t–x PhIO,4y and trichloroisocyanuric acid with 2,2,6,6-tetramethylpiperidi- nooxy (TEMPO).4z However, there are only a few reports on the direct oxidative conversion of alcohols as starting materials into nitriles in a one-pot procedure, i.e. using NH4HCO3, (Bu4N)2S2O8, and a catalytic amount of Cu(HCO2)2·Ni(HCO2)2 in aqueous KOH and i-PrOH,5a and MnO2, NH3, and MgSO4 in THF and i-PrOH for benzylic and cinnamic alcohols.5b

As a part of our basic study of molecular iodine and related reagents for organic synthesis, we previously reported an efficient preparation of nitriles from the alcohols6a and amines6b using molecular iodine. Here, we would like to

SYNLETT 2007, No. 3, pp 0407–0410 Advanced online publication: 07.02.2007

DOI: 10.1055/s-2007-967954; Art ID: U14106ST © Georg Thieme Verlag Stuttgart · New York

report another direct, efficient, practical and less toxic oxidative conversion of primary alcohols, and primary, secondary, and tertiary amines into the corresponding nitriles, using 1,3-diiodo-5,5-dimethylhydantoin (DIH) in aqueous ammonia. Today, to the best of our knowledge, synthetic use of DIH is extremely limited, whereas the iodination of aromatics with DIH has been reported.7

Thus, the present reaction was carried out very simply by treatment of dodecanol and dodecylamine (1 mmol) with DIH (2.0 mmol for dodecanol and 1.2 mmol for dodecylamine) in aqueous ammonia (28-30%, 3 mL) at 60 °C under dark conditions to provide the corresponding lauronitrile8 in 97% and 88% yields, respectively, as shown in Table 1 (entries 1 and 5). When the same reaction was carried out with NIS (4.0 mmol for dodecanol and 2.4 mmol for dodecylamine) in aqueous ammonia, lauronitrile was also obtained (entries 2 and 6). However, the yields were lower as compared with that obtained with DIH. On the other hand, NCS and NBS did not provide the corresponding lauronitrile at all, and the starting materials were recovered (entries 3, 4, 7, and 8).

Table 1 Oxidative Conversion of Dodecanol and Dodecylamine into Lauronitrile with DIH and Related Reagents in Aqueous Ammonia

aIsolated yield.

bRecovered starting material.

Various primary alcohols and benzylic alcohols were treated with DIH (1.5-2.0 equiv) in aqueous ammonia under the same conditions, as shown in Table 2.8 Yields of the reaction in which the flask was protected from room light with aluminum foil, was slightly better than those in which the flask was not protected from room light (entries 1 and 2). The reactivity depends on the alcohols used; thus

Table 2 Oxidative Conversion of Alcohols into Nitriles with DIH in Aqueous Ammonia

aIsolated yield.

bFlask was not covered with aluminum foil.

cDouble amount of aq NH3 was used.

benzylic alcohols were smoothly converted into the corresponding nitriles in good yields, using 1.5 equivalents of DIH, while aliphatic primary alcohols required 2 equivalents of DIH and longer reaction time. The treatment of 1,8-octanediol and p-xylene glycol in an analogous manner provided the corresponding dinitriles in good yields (entries 6 and 7). Then the reactions of primary, secondary, and tertiary amines with DIH in aqueous NH3 were carried out as shown in Table 3. Primary and benzylic amines smoothly reacted with DIH in aqueous NH3 to give the corresponding nitriles in good yields.8 Decan- 1,11-diamine generated the corresponding dinitrile using 2.4 equivalents of DIH (entry 10). When N-methyl secondary amines and N,N-dimethyl tertiary amines were treated with DIH under the same conditions, the corresponding nitriles could be again obtained in good yields (entries 11-14). Moreover, bis(dodecyl)amine (1 mmol),

Table 3 Oxidative Conversion of Amines into Nitriles with DIH in Aqueous Ammonia

Cl

aIsolated yield.

bAqueous NH3 (6 mL) was used.

cAqueous NH3 (9 mL) was used.

dAqueous NH3 (3 mL) was added again after 24 h.

and tris(dodecyl)amine (1 mmol), were treated with 2.4 equivalents and 3.6 equivalents of DIH, in aqueous ammonia under the same conditions to provide the corresponding lauronitrile in 84% and 84% yields, respectively (entries 15 and 16).

A plausible reaction pathway for the conversion of primary alcohol and primary amine into nitrile is shown in Scheme 1. According to this pathway, the initial O-iodi- nation and N-iodination of alcohol and amine with DIH occurs to form the O-iodo and N-iodo compounds (a), respectively, followed by b-elimination of HI by ammonia to form aldehyde and aldimine (b), respectively. Here the aldehyde reacts with ammonia to form aldimine (c). Then, aldimine (c) reacts with DIH in the presence of

ammonia to form N-iodo aldimine (d), followed by b- elimination of HI by ammonia to generate the corresponding nitrile.6 Practically, aldehydes react with DIH smoothly at room temperature in aqueous ammonia to provide the corresponding nitriles in good yields. Imines also react with DIH in aqueous ammonia to form the corresponding nitriles in good yields.

R CH2 XH R C≡N

Scheme 1 Plausible reaction pathway for nitrile

In summary, DIH can be used as an efficient reagent for the conversion of primary alcohols, and primary, secondary, and tertiary amines into the corresponding nitriles in good yields in aqueous ammonia. DIH has almost the same reactivity as molecular iodine. However, DIH is a pale yellow solid and does not sublimate like molecular iodine. So it is more convenient to operate the reaction with DIH. The present method using DIH may become another simple and useful method for the direct oxidative conversion of primary alcohols, and primary, secondary, and tertiary amines into the corresponding nitriles, along with molecular iodine. Further synthetic study of DIH is underway in this laboratory.

Acknowledgment

Financial support from Forum on Iodine Utilization is gratefully acknowledged. The authors thank Nippoh Chemicals Co. for the gift of DIH.

References and Notes

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(8)Typical Experimental Procedure for Oxidative Conversion of Primary Alcohols into Nitriles:9 To a

mixture of dodecanol (186.3 mg, 1 mmol) and aq NH3 (3.0 mL, 45 mmol) was added DIH (731.9 mg, 2.0 mmol) at r.t. under an empty balloon. The obtained mixture was stirred at 60 °C. After 32 h at the same temperature, the reaction

mixture was quenched with H2O (20 mL) and sat. aq Na2SO3 (3 mL) at 0 °C, and was extracted with Et2O (3 × 15 mL). The organic layer was washed with brine and dried over

Na2SO4 to provide lauronitrile in 97% yield in an almost pure state. If necessary, the product was purified by column chromatography on silica gel (hexane-EtOAc, 4:1) to give pure lauronitrile in 97% yield as a colorless oil. IR (NaCl):

2250 cm-1. 1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.29 (br, 14 H), 1.45 (quin, J = 7.1 Hz, 2 H), 1.66 (quin, J = 7.1 Hz, 2 H), 2.34 (t, J = 7.1 Hz, 2 H). The product

was identified by comparison with the commercially available authentic compound.

Typical Experimental Procedure for Oxidative Conversion of Primary Amines into Nitriles:9 To a mixture of dodecylamine (185.4 mg, 1 mmol) and aq NH3 (3.0 mL, 45 mmol) was added DIH (439.1 mg, 1.2 mmol) at r.t. under an empty balloon. The obtained mixture was stirred at 60 °C. After 6 h at the same temperature, the reaction mixture was quenched with H2O (20 mL) and sat. aq Na2SO3 (3 mL) at 0 °C, and was extracted with Et2O (3 × 15 mL). The organic layer was washed with brine and dried over Na2SO4 to provide lauronitrile in 88% yield in an almost pure state. If necessary, the product was purified by column chromatography on silica gel (hexane-EtOAc, 4:1) to give pure lauronitrile as a colorless oil.

(9)All nitriles gave satisfactory spectroscopic data and were identified by comparison with commercially available authentic materials.