Acylation, nitroalkanes

Higher nitroalkanes are prepared from lower primary nitroalkanes by a one-pot synthesis (69). Successive condensations with aldehydes and acylating agents are followed by reduction with sodium borohydride. Overall conversions in the 75—80% range are reported. 

Although acyl imidazoles can be replaced by phenyl esters in some cases," acyl imidazoles are more effecdve for the acyladon of nitroalkanes A combinadon of diethyl phosphorcyani-dates and triethylamime allows the direct C-acyladon of nitromethane by aromadc carboxylic... 

In general, heterocyclic nitro compounds undergo cine snbsdtudon reacdons more readily than nltrobenzenes For example, the reacdon of 5-acyl- or 5-alkoxycarbonyl-2-nitrofurans v/ith the anion of nitroalkanes gives cine snbsdtudon products in excellent yields fEq 5 66 ... 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

The only possible acyl anion disconnection is (33b) which requires (36). A nitroalkane is ideal for this. 

Daubner SC, G Gadda, Mp Valley, PF Fitzpatrick (2002) Cloning of nitroalkane oxidase from Fusarium oxysporum identifies a new member of the acyl-CoA dehydrogenase superfamily. Proc Natl Acad Sci USA 99 2702-2707. 

Nitroalkanes can be acylated by imidazolides via their sodium, potassium, lithium, or ammonium salts in refluxing THF or in DMSO. Acylation in this case takes place exclusively at the a-carbon of the nitro compound. 

The Michael addition of nitroalkanes to a,P-unsaturated ketones followed by the Nef reaction has been extensively used as a method for the conjugated addition of acyl anions to enones (see Section 6.1, Nef Reaction). This strategy is one of the best methods for the preparation of 1,4-dicarbonyl compounds.156a h Various natural products have been prepared via this route.157 For example, r/.v-jasmone is prepared from readily available materials, as shown in Scheme 4.19.156f... 

The acylation of the carbanions derived from nitroalkanes with acyl imidazoles or alkoxy-carbonylimidazoles takes place at the carbon atom to yield a-nitro ketones or a-nitro esters, respectively (Eq. 5.10).21 The lithium salts of nitroalkanes were isolated and used in THF or DMSO in the original procedure. Later, potassium salts generated in situ on treatment with r-BuOK in DMSO are reactive enough to give a-nitro ketones in good yield (Eq. 5.11).22... 

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... 

Bachmann and Biermann reported the synthesis of nitroalkanes from the thermolysis of acyl nitrates. The thermolysis of nitrite and nitrate esters over an asbestos catalyst is also reported to yield nitroalkanes. ... 

Another important part of Organic 11 is carbonyl chemistry. We look at the basics of the carbonyls in Chapter 9. It s like a family reunion where 1 (John, one of your authors) grew up in North Carolina — everybody is related. You meet aldehydes, ketones, carboxylic acids, acyl chlorides, esters, cimides, and on and on. It s a quick peek, because later we go back and examine many of these in detail. For example, in Chapter 10 you study aldehydes and ketones, along with some of the amines, while in Chapter 11 we introduce you to other carbonyl compounds, enols and enolates, along with nitroalkanes and nitriles. 

Nitroalkanes are easily functionalized with a variety of acylating agents such as phenyl isocyanate, acetic anhydride, and ethyl chloroformate in the presence of a... 

The usefulness of the nitronate anion from a primary nitroalkane as an acyl anion equivalent (see Appendix A6.2) is further illustrated by the fact that it may be reacted with other electrophiles, prior to the conversion into the carbonyl group.120 An example of its use in this manner is illustrated in Expt 5.178. 

Convenient reagent equivalents could be a nitroalkane (for the acyl anion syn-thon, p. 627), and acrolein or an acrylic ester (for the carbocation). The reaction would then be a Michael addition process (Section 5.11.6, p. 681), followed by functional group modification (e.g. C—N02 to 0=0, p. 599, and CHO to C02H, p. 667). 

Acylated 2-aminopyrazole 1-oxides 118 were prepared in excellent yields by heating (5-nitroacylhydrazones 117 to reflux with sodium methoxide in methanol (2006SL2731). The nitroacylhydrazones 117 were synthesized by treatment of 2-diaza-l,3-butadienes 115 with nitroalkanes 116 and catalytic amounts of sodium methoxide under solvent-free conditions at room temperature. The nitroalkane anion adds to the hydrazone 115 in a conjugated fashion producing diastereomeric mixtures of nitroac-ylhydrazone 117 in high yields (Scheme 36). 

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