Nitro alcohols reduction

The synthesis of ephedrine shown in Method H is of commercial interest (316). Condensation of benzaldehyde with nitroethane gives a diastereomeric mixture of nitro alcohols. Reduction yields a separable mixture of ( )-norephedrine and ( )-norpseudoephedrine. Methylation of ( )-norephedrine yields ( )-ephe-drine, which can be resolved into optical antipodes by chemical methods. 

The nitro alcohols can be reduced to the corresponding alkan olamines (qv). Commercially, reduction is accompHshed by hydrogenation of the nitro alcohol in methanol in the presence of Raney nickel. Convenient operating conditions are 30°C and 6900 kPa (1000 psi). Production of alkan olamines constitutes the largest single use of nitro alcohols. 

The nitro alcohols are useful as intermediates for chemical synthesis. In particular, they are used to introduce a nitro functionaHty and, by reduction of the resultant intermediate, an amino functionaHty. 

The reduction of nitro alcohols to alkanolamines is readily accompHshed by hydrogenation in the presence of Raney nickel catalyst (1,9,10). 

The cyclization reaction could also be carried out before the reduction of the nitro group. The resulting nitro alcohols were then converted toPGEi and l5-epi- and 11,15-epi-PGEi s. 

Jdger and co-workers have prepared various amino sugars by the reduction of the con sponding fi-nitro alcohols with H-, and Pd/C, as exemplified in Eq 6 49 fsee Chapter 3 ... 

The reduction of fi-nitro alcohols v/ith ammonium formate in the presence of Pd/C also proceeds v/ith retendon of their configuradons fEq. 6.53. ... 

Nitro alcohols prepared by the Henry reaction are important precursors for (3-amino alcohols. The reduction of the nitro group to the amino function is commonly carried out by hydrogenation in the presence of Raney Ni in EtOH or Pd/C in THF and MeOH (see Section 4.2). The conversion into 3-amino alcohols is also described in the Sections 3.2.5 and 3.3. 

Regioselective reduction of 2-nitrocycloalkanones with sodium borohydride affords co-nitro alcohols. This reaction is applied to the synthesis of spiroketals as shown in Eq. 5.17, in which spiro[4,5]- and spiro[4,6]ketal systems are obtained in good yields.32... 

The reduction of P-nitro alcohols with LiAlH4 results in low yields of P-amino alcohols due to the occurrence of a retro-aldol reaction. This problem is resolved by protecting of OH of P-nitro alcohols, as shown in Eq. 6.53."... 

Various other reducing methods are employed for the conversion of (3-nitro alcohols to amino alcohols, namely, electrochemical reduction.107 The selective electrohydrogenation of ni-troaliphatic and nitroaromatic groups in molecules containing other groups that are easy to hydrogenate (triple bond, nitrile, C-I) are carried out in methanol-water solutions at Devarda copper and Raney cobalt electrodes (Eq. 6.55).107... 

The sonochemical-promoted aluminum amalgam reduction of P-nitro alcohols provides an improved yield and accelerated conversion to the corresponding amino alcohols.108... 

The reduction of nitro ketones with baker s yeast is a good method for the preparation of chiral nitro alcohols.89 The reduction of 5-nitro-2-pentanone with baker s yeast gives the corresponding (5)-alcohol, which is an important chiral building block. Various chiral natural products are prepared from it. In Scheme 7.16, the synthesis of the pheromone of Andrena haemorrhoa is described, where the acylation of the chiral nitro alcohol followed by radical denitration is involved as key steps.89a... 

Baker s yeast reduction of y-nitroketones offers the corresponding chiral nitro alcohols, which are useful building blocks for the synthesis of chiral natural compounds.120 For example, optically active 2-substituted pyrrolidine can be prepared using the chiral nitro alcohol (Eq. 10.75).121... 

The enantioselective reduction of y-nitroketones and y-nitrodiketones by the chiral reducing agent (+)- or (-)-dusopinocamphenylchloroborane (DIP-C1 ) gives nitro alcohols having from 33 to 86% ee and nitrodiols with complete diastereoselectivity and > 95% ee.122... 

Selective reduction of the ester function in products (37), step (2), affords nitro alcohols (38), which are either transformed into halo-containing compounds... 

Selective reduction of the oximino fragment in products (224) or (225) gives rise to poorly studied y-amino alcohols (226). In addition, desoximation of (225) can produce the corresponding p-hydroxycarbonyl derivatives (227). In addition, oximino alcohols (225) can be oxidized to y-nitro alcohols (228). 

For example, the 0,C-trisaccharide 153 was obtained by a Henry reaction of nitro disaccharide 151 and sugar aldehyde 150 followed by the dehydration of (3-nitro alcohol 152 and reduction of the resulting nitroolefin, to give nitro sugar 153. Finally, a radical elimination of the nitro group afforded the target 154 (Scheme 47).105... 

In nitro aldehydes both the nitro group and the aldehyde group are readily reduced by catalytic hydrogenation. It may be difficult, if not impossible to hydrogenate either function separately. More dependable methods are reduction by alane [787] or by isopropyl alcohol and aluminum isopropoxide Meerwein-Ponndorf) [788] to nitro alcohols, and by stannous chloride [789, 790], titanium trichloride [590] or ferrous sulfate [218] to amino aldehydes Procedure 38, p. 214). 

The reduction of ketones containing nitro groups to nitro alcohols is best carried out by borohydrides. 5-Nitro-2-pentanone was converted to 5-nitro-2-pentanol in 86.6% yield by reduction with sodium borohydride at 20-25°. Other nitro ketones gave 48.5-98.7% yields, usually higher than were obtained by Meerwein-Ponruiorf reduction [907]. 2-Acetamido-3-(p-nitrophenyl)-l-hydroxypropan-3-one was reduced with calcium borohydride at — 30° to 70% of threo- and 10% of er7tAro-2-acetamido-3-(p-nitrophenyl)propane-l,3-diol while sodium borohydride afforded a mixture of the above isomers in 25% and 47% yields, respectively [902]. 

Iron and acetic or dilute hydrochloric acid can be safely used for the reduction of nitro group to an amino group in nitro esters. The problem arises when a nitro ester is to be reduced to a nitro alcohol. Nitro groups are not inert toward the best reagents for the reduction of esters to alcohols, complex hydrides. However the rate of reduction of a nitro group by lithium... 

Much more spectacular were the selectivity variations in the case of 3-nitro-benzaldehyde reduction (Table 3). Depending on the hydrogen donor used 3-nitro-benzyl alcohol (methanol, 450°C) or 3-aminobenzaldehyde (i-propanol, 450°C) were the main reaction products. 

Nitro alcohols are nonaromatic compounds containing both -OH and -N02 groups. A typical example of such a compound is 2-nitro-l-butanol, shown below. These compounds are used in chemical synthesis to introduce nitro functional groups or (after reduction) amino groups onto molecules. They tend to have low volatilities and moderate toxicities. The aromatic nitrophenol, / -nitrophenol, is an industrially important compound with toxicological properties resembling those of phenol and nitrobenzene. 

Wiiat procedure is available for preparing 0-amino alcohols Answer Procedure XIV-3 which involves the catalytic reduction of a 0-nitro alcohol. Thus we need A. 

They include aromatic hydroxylation, hydrocarbon and alcohol oxidation, alkene epoxidation, nitro-aromatic reduction, dehydrogenation, carbonylation, cyclization, heterocycle functionalization, etc. 

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