Ammonium borohydride reducing

Polymeric Quaternary Ammonium Borohydride Reducing Agents... 

Although there is evidence that quaternary ammonium salts are cleaved by sodium borohydride at high temperature [7], initial studies suggested that the quaternary ammonium borohydrides might have some synthetic value in their selectivity, e.g. aldehydes are reduced by an excess of the quaternary ammonium salts under homogeneous conditions in benzene at 25 °C, whereas ketones are recovered unchanged and are only partially reduced at 65 °C [2], The reduction of esters also requires the elevated temperature, whereas nitriles are not reduced even after prolonged reaction at 65 °C. Evidence that the two-phase (benzene water) reduction of octan-2-one by sodium borohydride was some 20-30 times faster in the presence of Aliquat, than in the absence of the catalyst [8], established the potential use of the mote lipophilic catalysts. 

Much emphasis has been placed on the selectivity of quaternary ammonium borohydrides in their reduction of aldehydes and ketones [18-20]. Predictably, steric factors are important, as are mesomeric electronic effects in the case of 4-substituted benzaldehydes. However, comparison of the relative merits of the use of tetraethyl-ammonium, or tetra-n-butylammonium borohydride in dichloromethane, and of sodium borohydride in isopropanol, has shown that, in the competitive reduction of benzaldehyde and acetophenone, each system preferentially reduces the aldehyde and that the ratio of benzyl alcohol to 1-phenylethanol is invariably ca. 4 1 [18-20], Thus, the only advantage in the use of the ammonium salts would appear to facilitate the use of non-hydroxylic solvents. In all reductions, the use of the more lipophilic tetra-n-butylammonium salt is to be preferred and the only advantage in using the tetraethylammonium salt is its ready removal from the reaction mixture by dissolution in water. 

A useful method for the reductive conversion of elemental tellurium into Te anions employs complex hydrides such as sodium or potassium borohydride and tetraalkyl ammonium borohydride as reducing agents. 

Polymer-bound reagent. Reaction of a quaternary ammonium anion-exchange resin (Amberlites) wth NaBH4 results in an immobilized borohydride reducing agent (1), which is somewhat less reactive than NaBH4.4... 

Nitropyridine is reduced to 4-aminopyridine by sulfur dioxide dissolved in dilute sulfuric acid containing hydrogpn iodide as a catalyst. " Aqueous solutions of sodium sulfide or ammonium sulfide reduce only the 3-nitro substituent in 3,5-dinitropyiidine and 3,5-dinitro-2-pyridone. " " 4-Nitro-2,6-lutidine-1-oxide (IX-17) reacts with aqueous hydrosulfite to give 4-amino-2,6-lutidine (K-18) " however, IX-17 reacts with sodium borohydride to give 4,4 -azo-2,6-lutidine-l, 1 -dioxide (DC-19). " ... 

Using a condensed reaction form, treatment of 2-butanone with NaBI leads to 2-butanol, and the first step delivers the hydrogen marked in blue in the illustration, whereas aqueous ammonium chloride (a weakly acidic solution) is the second step that delivers the hydrogen marked in red. Sodium borohydride reduces both ketones and aldehydes. Indeed, the reduction of an aldehyde with NaBH4 is somewhat easier than the similar reduction of a ketone. Aldehydes are easier to reduce than ketones because the carbonyl unit is less stericaUy hindered. 

The desire for a mild reducing reagent like borohydride which would be soluble in nonpolar media has led to the development of several ammonium borohydrides. 

The reducing power of tetralkylammonium borohydrides in dichloromethane is similar to that observed in water or alcohol. A convenient preparation of tetrabutyl-ammonium borohydride has recently been reported [11] and the utility of the reagent has been surveyed [12]. In dichloromethane solution, tetrabutylammonium borohydride readily reduces aldehydes, ketones and acid chlorides while reacting only very slowly with esters (see Table 12.2). 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

Heat 3-nitrophthalic anhydride with ammonium carbonate to get 3-nitrophthalimide (I). Dissolve 4.3 g (I) in 50 ml 90% methanol and add 1.9 g sodium borohydride over 30 minutes while stirring vigorously at room temperature. Stir 2 hours, acidify with 20% HCI, evaporate in vacuum and treat the dry residue with acetone. Evaporate in vacuum to get 3.9 g (88%) 3-OH-4-nitrophthal-imidine (II) (recrystallize from acetone). Dissolve 3.9 g (II) in 40 ml 20% HCI and stir for 10 hours on water bath at 80-90°. Distill off HCI and stir residue with acetone. Filter and evaporate in vacuum to get 3.4 g 3-OH-4-nitrophthalide (III) (recrystallize from CHC 3 and can purify on column). Prepare an ether solution of CH2N2 and add to 1.93 g (III) in a 100 ml flask until a reaction is no longer evident. Add acetic acid to decompose excess diazomethane and evaporate in vacuum to get about 2 g of 2-methoxycarbonyl-6-nitrostyrene oxide (IV) (can purify on column). Dissolve 560 mg (IV) in 50 ml absolute methanol, add 50 mg Pt02 and hydrogenate as described elsewhere here (other reducing methods should work). Filter,... 

One-pot conversions of 2-hydroxy(acylbenzenes) with anhydrides or acid chlorides to produce coumarins [52-54] and flavones [54-58] under mild liquiddiquid or solidtliquid two-phase conditions via a Baker-Venkataraman type reaction (Scheme 6.19) are catalysed by quaternary ammonium salts. 3-Substituted coumarins are produced from salicylaldehyde and malonodinitrile, or substituted acetonitriles, in high yield (>85%) in a one-pot catalysed sequential aldol-type reaction and cycliza-tion in the absence of an added organic solvent [59]. When 2 -hydroxychalcones are reduced under catalytic two-phase conditions with sodium borohydride, 2,4-cis-flavan-4-ols are produced [60] (see Section 11.3). 

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

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