Reductions with Acetals

Reduction of ketones with sodium borohydride in the presence of a carboxylic acid and 1,2 5,6-di-0-cyclohexylidene-a -D-glucofuranose gave 35-50% enantiomeric enhancement values.Another group has reported a similar reaction with the corresponding di-O-isopropylidene-glucose derivative and prochiral aromatic ketones. Optical yields of up to 64% were claimed. The chiral reagents appear to be sodium acyloxyborohydrides, which complex with the carbohydrate before reduction takes place. 

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Dioxabicyclo[3.2.1]octan-4-one, enone 1,2-reduction with acetal, 129-130 Disubstituted alkenes, alkene to alkane reductions, 36-38... 

Addition of perchloric acid to the ester 7b gave a reversible reduction wave with an E1/2 of -0.45 V. The amide 7c reduced irreversibly with perchloric acid (Ep -0.56 V). An Ep of -0.68 V was obtained for the irreversible reduction with acetic acid. 2-Phenylquinoline also reduced irreversibly in perchloric and acetic acids resulting in Ep values of -0.56 V and -0.63 V, respectively. 

Trichloro- and 2,2,2-tribromoethoxycarbonyl (Tceoc and Tbeoc) protecting groups are introduced with the commercially available 2,2,2-trihaloethyl chloroformates. These derivatives are stable towards CrOj and acids, but can smoothly be cleaved by reduction with zinc in acetic acid at 20 °C to yield 1,1-dihaloethene and CO. Several examples in lipid (F.R. Pfeiffer, 1968, 1970) and nucleotide syntheses (A.F. Cook, 1968) have been described. 

Acetate, (reduction with) ascorbic acid + KI, citrate, V,V-dihydroxyethylglycine, EDTA, F , formate, NaOH + H2O2, oxidation to CrOJ , NagP30io, sulfosalicylate, tartrate, triethylam-ine, tiron... 

Ethynodiol diacetate (53) is prepared by reduction of the 3-oxo group of norethindrone (28) with lithium tributoxyalurninum hydride, followed by acylation with acetic anhydride-pyridine (78,79). It has been reported that higher yields can be obtained in the reduction step by using triethylanainoalurninum hydride (80). 

Isophorone usually contains 2—5% of the isomer P-isophorone [471-01-2] (3,5,5-trimethyl-3-cyclohexen-l-one). The term a-isophorone is sometimes used ia referring to the a,P-unsaturated ketone, whereas P-isophorone connotes the unconjugated derivative. P-lsophorone (bp 186°C) is lower boiling than isophorone and can be converted to isophorone by distilling at reduced pressure ia the presence of -toluenesulfonic acid (188). Isophorone can be converted to P-isophorone by treatment with adipic acid (189) or H on(Ill) acetylacetoate (190). P-lsophorone can also be prepared from 4-bromoisophorone by reduction with chromous acetate (191). P-lsophorone can be used as an iatermediate ia the synthesis of carotenoids (192). 

Derivatives. Oxidation of pyrogaHol trimethyl ether with nitric acid, followed by reduction ia acetic anhydride and treatment of the product with aluminum chloride, affords 3,6-dihydroxy-2,4-dimethoxyacetophenone (228). 3,4,5-Trimethoxyphenol (antiarol) has been prepared by treatment of... 

The compound can be prepared from 2,4,6-trinitrophenol (picric acid [88-89-1]) by reduction with sodium hydrosulfide (163), with ammonia —hydrogen sulfide followed by acetic acid neutralization of the ammonium salt (164), with ethanolic hydrazine and copper (165), or electrolyticaHy with vanadium sulfate in alcoholic sulfuric acid (159). Heating 4,6-dinitro-2-benzamidophenol in concentrated HQ. at 140°C also yields picramic acid (166). 

The compound is odorless with a faintly acidic taste it is practically insoluble in water, ethanol and dilute acids but freely soluble in dilute aqueous alkaU with dissociation constants, pfC, 3.73, 7.9, 9.3. The compound is prepared by sodium hydrosulfite reduction of 3-nitro-4-hydroxyphenylarsonic acid [121 -19-7] and then acetylation in aqueous suspension with acetic anhydride at 50—55°C for 2 h (174,175). 

Production is by the acetylation of 4-aminophenol. This can be achieved with acetic acid and acetic anhydride at 80°C (191), with acetic acid anhydride in pyridine at 100°C (192), with acetyl chloride and pyridine in toluene at 60°C (193), or by the action of ketene in alcohoHc suspension. 4-Hydroxyacetanihde also may be synthesized directiy from 4-nitrophenol The available reduction—acetylation systems include tin with acetic acid, hydrogenation over Pd—C in acetic anhydride, and hydrogenation over platinum in acetic acid (194,195). Other routes include rearrangement of 4-hydroxyacetophenone hydrazone with sodium nitrite in sulfuric acid and the electrolytic hydroxylation of acetanilide [103-84-4] (196). 

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

Reduction. Triaryknethane dyes are reduced readily to leuco bases with a variety of reagents, including sodium hydrosulfite, 2inc and acid (hydrochloric, acetic), 2inc dust and ammonia, and titanous chloride in concentrated hydrochloric acid. Reduction with titanium trichloride (Knecht method) is used for rapidly assaying triaryknethane dyes. The TiCl titration is carried out to a colorless end point which is usually very sharp (see Titanium COMPOUNDS, inorganic). 

Vanillin, being an aldehyde, is able to form acetals and hemiacetals. Therefore, in flavor formulations using high concentrations of vanillin in conjunction with carriers such as propylene glycol, a glc analysis often shows a reduced vanillin peak after storage of the compounded flavor, and the presence of new peaks indicating acetal formation. Addition of about 0.5% of water to the formula reverses the reaction, ie, there is a reduction of acetal, and the reappearance of vanillin peaks. 

Later, a completely different and more convenient synthesis of riboflavin and analogues was developed (34). It consists of the nitrosative cyclization of 6-(A/-D-ribityl-3,4-xyhdino)uracil (18), obtained from the condensation of A/-D-ribityl-3,4-xyhdine (11) and 6-chlorouracil (19), with excess sodium nitrite in acetic acid, or the cyclization of (18) with potassium nitrate in acetic in the presence of sulfuric acid, to give riboflavin-5-oxide (20) in high yield. Reduction with sodium dithionite gives (1). In another synthesis, 5-nitro-6-(A/-D-ribityl-3,4-xyhdino) uracil (21), prepared in situ from the condensation of 6-chloro-5-nitrouracil (22) with A/-D-ribityl-3,4-xyhdine (11), was hydrogenated over palladium on charcoal in acetic acid. The filtrate included 5-amino-6-(A/-D-ribityl-3,4-xyhdino)uracil (23) and was maintained at room temperature to precipitate (1) by autoxidation (35). These two pathways are suitable for the preparation of riboflavin analogues possessing several substituents (Fig. 4). 

In the thiophene and selenophene series, a-halogens are preferentially removed by reduction with zinc and acetic acid, as is illustrated by the preparation of 3-bromothiophene... 

The electrochemical reduction of 3-nitrophthalic acid at controlled potentials gave 2,1-benzisoxazole-3-carboxylic acid. Cyclization is presumed to proceed via an intermediate oxime (67AHC(8)277). Treating 5-iodoanthranilic acid with acetic anhydride gave 3-acetoxy-5-iodo-2,l-benzisoxazole (596) (65JMC550). 

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of stmcture. The most useful compounds do not necessarily have the simplest stmctures, but are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hy-drogenolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and ally], readily cleaved by Pd-catalyzed isomerisation. 

Snyder and Smith prepared diethyl acetamidomalonate in 40% yield by reduction of diethyl isonitrosomalonate in ethanol over palladium on charcoal followed by direct acetylation of diethyl aminomalonate in the filtrate with acetic anhydride. Ghosh and Dutta used zinc dust instead of palladium. A modification using Raney nickel is described by Akabori et al. Shaw and Nolan reported a 98% yield by conversion of diethyl oximino-malonate-sodium acetate complex. 

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