NaBH 4 / NaNO 3 / H 2 O : A Convenient System for Selective Reduction of Aldehydes VS . Ketones to their Corresponding Alcohols

NaBH4 (1.25 equivalents) & NaNO3 (3 equivalents) reduce a variety of aldehydes in the presence of ketones to their corresponding alcohols. Also, regioselectivity and exclusive 1,2reduction enals to their corresponding allylic alcohols in high to excellent yields was achieved successfully with this reducing system. The reduction reactions were carried out in water as green solvent in high to excellent yields of the products. A nitrate-borane complex [H3B-NO3]Na is possibly the active reductant in the reaction mixture.


RESULTS AND DISCUSSION
Ketones are less reactive than aldehydes in reduction reactions. But this character is not sufficient for selectively reduction of aldehydes vs. ketones (scheme 1, Path A). To achieve for more selectivity, the reduction reactions can be done slower. For this purpose we have examined the reduction reaction of benzaldehyde as model compound with NaBH 4 in aqueous media in the presence and absence of NaNO 3 as shown in scheme 1. Our observation showed that the reduction reaction of 1 eq. benzaldehyde completed at room temperature in the presence of 3 eq. NaNO 3 and 1.25 eq. NaBH 4 as shown in table 1.
For investigate of selectively reduction reaction, a mixture of benzaldehyde (1 eq.) and acetophenone (1 eq.) was prepared. The reaction mixture was treated with 1.25 equivalents of NaBH 4 and 3 equivalents of NaNO 3 in 3 mL water at room temperature. As shown in scheme 1, after 30 min, we have observed that the reduction of benzaldehye to benzyl alcohols was complete but acetophene was intact material i.e. the competition for reduction was favor of benzaldehyde (scheme 1, path B). This result can not achieve by only using NaBH 4

Scheme 1:
The efficiency of this protocol was examined by the reduction of a variety of aldehydes in the presence of acetophenone. All reductions were completed within 30-180 min as shown in table 2. The molar ratio of NaBH 4 is not different according to the nature of the substrates. 1.25 molar equivalents of NaBH 4 and 3 molar equivalents of NaNO 3 per one equivalents of the substrate were sufficient to complete conversion of aldehydes to the corresponding alcohols in excellent yields (90-95%).
For more investigate, the reduction of 6oxoheptanal and 4-acetylbenzaldehyde as ketoaldehydes to their corresponding ketoalcoholes has been done as shown in scheme 2. The reductions were completed within 50-65 min and the corresponding ketoalcoholes have been isolated in excellent yields (90-92%). The preparation of ally alcohols from the reduction of conjugated carbonyl compounds is conventional in organic synthesis. Regioselective 1,2-reduction of ,-unsaturated aldehydes due to competing 1,2-vs. 1,4-attack by the hydride is often difficult to achieve in organic synthesis. The tendency of sodium borohydride to reduce enals in a conjugate sense is highly dependent on solvent and often ignored. 14 However, several specific reagents are available. 15 In this context, we also investigated the possibility of the 1,2-reduction of ,-unsaturated aldehydes and ketones with NaBH 4 /NaNO 3 /H 2 O system. The reduction of cinnamaldehyde by 1.25 molar equivalents of NaBH 4 in the presence of 3 molar equivalents of NaNO 3 was thus carried out exclusively in 1,2reduction manner within 40 minutes at room temperature. In this reaction, cinnamyl alcohol was obtained in 94% yield as shown in scheme 3 ( Table  2, entry 9). Citral also showed the best efficiency and regioselectivity under this protocol ( The mechanism for the influence of NaNO 3 is not clear, but as shown in scheme 4 we think that a possible derivative of nitrate-borane as active reductant may form in situ under reaction condition. The possibility to form borane complex via nucleophilic attack is also well-known [16][17] . The nitrate-borane specie is generated by the nucleophilic attack of nitrate ion on borane (scheme 4, II) formed from sodium borohydride and water (scheme 4, I). The nitrate-borate is less reactive than NaBH 4 and diminishes reactivity.

EXPERIMENTAL General
All substrates and reagents were purchased from commercially sources with the best quality. IR and 1 H NMR spectra were recorded on PerkinElmer FT-IR RXI and 300 MHz Bruker spectrometers, respectively. The products were characterized by their 1 H NMR or IR spectra and comparison with authentic samples (melting or boiling points). Organic layers were dried over anhydrous sodium sulfate. All yields referred to isolated pure products. The purity of products was determinate by 1 H NMR. Also, reactions are monitoring over silica gel 60 F 254 aluminum sheet. A typical procedure In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of NaBH 4 (0.047 g, 1.25 mmol) and NaNO 3 (0.255 g, 3 mmol) in water (3 mL) was treated with 6-oxoheptanal (0.128 g, 1 mmol) in one portion. The mixture was stirred at room temperature for 50 minutes. Completion of the reaction was monitored by TLC (Hexane/EtOAc: 9/1). Then, water (5 mL) was added to the reaction mixture. The mixture was extracted with ether (3×10 mL) and dried over anhydrous Na 2 SO 4 . Evaporation of the solvent afforded the pure 7-hydroxyheptan-2-one (0.236 g, 92%, Table 1, entry 7).

CONCLUSION
In conclusion, we have shown that NaBH 4 / NaNO 3 /H 2 O reduces a variety of aldehydes vs. ketones to their corresponding primary alcohols in high to excellent yields at room temperature. Reduction reactions were carried out with 1.25 molar equivalents of NaBH 4 in the presence of 3 molar equivalents of NaNO 3 in water as green solvent. In addition, regioselectivity of this system was also investigated with exclusive 1,2-reduction of conjugated enals to their corresponding allylic alcohols in excellent yields. All reductions were accomplished with high efficiency of the reductions, using the appropriate molar ratios of NaBH 4 and NaNO 3 , convenient reaction times (30-180 min) and easy work-up procedure. Therefore this new protocol for chemoselective & regioselective reduction of aldehydes could be a useful addition to the present methodologies.