Enol acetates nitration

Nitradon of the potassium enolates of cycloalkanones with pentyl n silyl enol ethers with nitroniiim tetraflnoroborate " provides a method for the preparadon of cydic ct-nitro ketones. Tnflnoroacetyl nitrate generated from tnflnoroacedc anhydnde and ammonium nitrate is a mild and effecdve nitradug reagent for enol acetates fEq. 2.411. ... 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

Nitration of enol acetates a-nitro ketones. This reagent is more useful than acetyl nitrate (AciO/HNOj) for nitration of enol acetates of cyclohexanones, particularly those of 2-alkyIcyclohexanones, which can undergo ring cleavage. However, yields are low unless the 2-substituent is a primary alkyl group. 

The popularity of the Nef reaction is due in part to the ready availability of nitro compounds. Primary and secondary halides react with sodium nitrite in dimeAyl sulfoxide (DMSO) or dimethylform-amide (DMF) to give useful yields of nitro compounds. Primary amines can be oxidized to nitro compounds with potassium permanganate, m-chloroperbenzoic acitP or ozone. Chlorination of oximes with hypochlorous acid and reduction with magnesium, zinc or hydrogen/lpalladium gives secondary nitro compounds. Stabilized carbanions can be nitrated by treauitent with a nitrate ester, and enol acetates are nitrated by acetyl nitrate to give nitro ketones. ... 

The reactions of acetyl nitrate, trifluoroacetyl nitrate, and nitronium tetrafluoroborate with enol acetates and trimethylsilyl enol ethers are described in Section 7.2.1.11. 

In a 25-mL flask equipped with a condenser are placed 3 mmol of the enol acetate, 0.24 g (3 mmol) of preground ammonium nitrate, and 3 ml of CHCf,. 3 mL of trifluoroacelic anhydride are then added, and the mixture is stirred at room temperature for 1 h. The resulting solution is diluted with 25 mL of CH2C12, and poured in 25 mL of ice/water. The aqueous layer is separated and extracted with two 20-mL portions of CH2C12. The combined organic layers are washed with 25 mL of cold 1 % aq NaHCO, 25 mL of sat. aq NaCl, and dried over anhyd MgS04, The solvent is evaporated to give the ot-nitro ketone cither as a viscous oil or a solid which is purified by either distillation or recrystallization. 

The nitration of enol acetates with acetyl nitrate is a regiospecific electrophilic addition to the 3-carbon of the enol acetate, followed by a hydrolytic conversion of the intermediate to the a-nitro ketone. With enol acetates of substituted cyclohexanones the stereochemistry is kinetically established. So, 1-acetoxy-4-methylcyclohexene (22) yields the thermodynamically less stable rrans-4-methyl-2-nitrocylo-hexanone (24) in greater proportion cis. trans = 40 60) (equation 8). This mixture can be equilibrated in favor of the thermodynamically more stable cis diastereomer (23) (cis. trans = 85 15). Nitration of 1-ace-toxy-3-methylcyclohexene (25) leads to frans-3-methyl-2-nitrocyclohexanone (26), which is also the thermodynamically more stable isomer (equation 9). No stereoselection occurs in the kinetically controlled nitration with acetyl nitrate of l-acetoxy-5-methylcyclohexene (27 equation 10), but the 1 1 mixture of the 5-methyl-2-nitrocyclohexanones can be equilibrated in favor of the trcms diastereomer (28) (cis trans = 10 90). 2-Alkyl-2-nitrocyclohexanones cannot be prepared in acceptable yields by nitration of the corresponding enol acetates with acetyl nitrate. 

It has been demonstrated that a mixture of ammonium nitrate and trifluoroacetic anhydride is a very effective system for the nitration of enol acetates. It is assumed that trifluoroacetyl nitrate is produced, which is a much more powerful nitrating agent than acetyl nitrate. So, 2-methyl-2-nitrocyclohexanone... 

Nitration of ketones. Direct nitration proceeded poorly and a-nitroketones were obtained in only low yield by use of the enol acetate. ... 

Nitrocyclohexanones" and 2-nitrocyclopentanones" are the products of the nitration of the corresponding cycloalkanone enol acetates. 

Nitration of Active Methylene Carbons. Active methylene carbons are nitrated by a number of reagents.With nitric acid the nitration of /S-diketones can be achieved (eq 7). Nitration of diethyl malonate provides diethyl nitromalonate in 92% yield. a-Nitro ketones are obtained by nitration of ketones or enol acetates with the reagent derived from nitric acid and acetic anhydride in moderate to good yields (eq 8). ... 

Reaction of TFAA with ammonium nitrate provides an in situ source of Uifluoroacetyl nitrate, which has been used for the nitration of enol acetates and as an iV-nitrating agent. ... 

Silyi enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in DMSO or certain other polar aprotic solvents." The reaction has been performed with R , R = hydrogen or alkyl, though best yields are obtained when r = r = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyi enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-Bp3-Et20," ceric ammonium nitrate," and lead tetraacetate." If R =0R (in which case the substrate is a ketene silyi acetal), dimerization with TiCU leads to a dialkyl succinate (34, r =0R)." ... 

Initial investigations in the Mannich-type reaction of silyl enolates with benzal-dehyde and aniline employed a series of bismuth(III) salts (Scheme 9, Table 10). These results were promising because the corresponding (l-amino ketone could be obtained in moderate to good yield with bismuth halides, except bismuth fluoride (Table 10, entries 1 1). Bismuth nitrate smoothly afforded the expected product (Table 10, entry 5). While bismuth acetate gave no conversion, bismuth trifluor-oacetate provided the product in only moderate yield (Table 10, entries 6 and 7). Phenyl bismuth ditriflate and diphenyl bismuth triflate appeared to be more efficient catalysts than all those previously tested (Table 10, entries 8 and 9). Bismuth(III) triflate led to the expected product in a good yield and in a short reaction time, without any difference between the anhydrous and the hydrated form (Table 10, entries 10 and 11). 

Monocyclic 1,2,3-triazines react with ketene silyl acetal, or silyl enol ether, in the presence of 1-chloroethyl chloroformate to give 5-(substituted)-2-(l-chloroethoxycarbonyl)-2,5-dihydrotriazines which are readily oxidised, and hydrolysed, with ceric ammonium nitrate in aqueous acetonitrile to 5-(substituted)-triazines (Scheme 24) [95CPB881],... 

Oxidation of cyclohexanone. Oxidation of cyclohexanone with TTN in acetic acid at room temperature proceeds rapidly to give adipoin (5) in 84% yield. If the oxidation is performed at first at room temperature, the thallium(I) nitrate removed hy filtration, and then the filtrate heated to about 40° for a few minutes, the product is cyclopentanecarboxylic acid (4), obtained in 84% yield. McKillop et al. propose that both products are derived from a common precursor, an epoxy enol (3). 

Acylainino-4-acylimidazoles have been made from 3-amino-l,2,4-oxadiazoles and 1,3-dicarbonyl reagents (see Section 2.2.1 and Scheme 2.2.5). 4(5)-Acylimidazoles can be derived from 4-acylaininoisoxazoles (see Section 6.1.2 and Scheme 6.1.3). (See also the discussion in Section 2.2.1 on 4-acylimidazole synthesis.) 5-Acyl-l-arylimidazoles can be made from or-oxoketene-SJV-acetals and nitrosoaromatics (see Section 3.2 and Scheme 3.2.5), and 4-acyl-imidazoles by nitration of 1,3-dicarbonyl compounds in their enolic forms, reduction to iV-alkenylformamides and subsequent cyclization (see Section 3.2 and Scheme 3.2.4). Examples have also been isolated from reactions of 2-oximino-l,2,3-tricarbonyls and amines (see Section 4.1 and Scheme 4.1.7), from compounds such as 3-chloro-4,4-dimethoxy-2-butanone and 3,4-disubstituted 3-buten-2-ones (see Section 4.3 and Scheme 4.3.5), and by ultraviolet irradiation of 1-alkenyltetrazoles which bear an acyl group conjugated with the exocyclic double bond (see Section 6.1.2.3). 

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