Acylation of Nitroalkanes

The carboxylation of nitroalkanes with magnesium methyl carbonate followed by esterification gives a-nitro esters in 40-58% yield.14 Magnesium methyl carbonate is prepared by the saturation of a magnesium methoxide suspension in DMF with C02. More elegantly, sodium salt of nitroalkanes can he carboxylated by means of 1 -ethoxycarbonylbenzotriazole to give a-nitro esters in 55-80% yield (Eq. 5.7).15 Nitroacetic acids and its esters can serve as useful 

Nitroacetaldehyde diethyl acetal is prepared by the reaction of nitromethane with triethyl orthoformate in the presence of ZnCl2 (Eq. 5.8).17 Jager and coworkers have used this reagent for the synthesis of amino sugars via nitro-aldol reaction.18 Preparation of this useful reagent is now described in volume 74 of Organic Synthesis.19 

Nitromethane reacts with triethyl orthoformate in the presence of secondary amines to give nitroenamines (Eq. 5.9).20 

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 

Although acyl imidazoles can be replaced by phenyl esters in some cases,23 acyl imidazoles are more effective for the acylation of nitroalkanes. A combination of diethyl phosphorcyani-dates and triethylamime allows the direct C-acylation of nitromethane by aromatic carboxylic 

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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... 

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 ... 

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. 

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... 

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. ... 

Aldehydes may be condensed with a nitroalkane and the resulting vicinal nitroalco-hol reduced to an alkene after acylation of the alcohol [85]. 

Ketoximes have been synthesized by Fujisawa using a catalytic Crul/Grignard addition to aci-nitroimi-nium chlorides, formed by 0-acylation of a nitroalkane with A(A(-dimethylchloromethyleninimium... 

The reaction of nitroalkanes with methoxymagnesium methyl carbonate represents an acylation by carbonic acid it affords good yields of <%-nitro carboxylic acids by way of a chelate-like intermediate 433... 

Nitriles. The oximation of nitroalkanes gives nitrolic acids, and further O-acylation and treatment with BUjSnH completes the transformation to nitriles. Iminyl radicals are generated from A-benzotriazolylimines, and the fate of such radicals is either cyclization or... 

The easy addition at C-5 of 1,2,4-triazines is shown by the VNS (section 2.3.3) reaction of the 3-methylthio-derivatives in the absence of activating groups a closely related addition of nitroalkanes represents a very useful nucleophilic acylation. The ready displacement of methylthio from the same compound is also indicative. " Nucleophilic displacement of methylthio in 1,2,4-triazines and 1,2,4,5-tetrazines by alkoxide and amines is very easy. Mono-displacement can be carried out on 3,6-bis(methylthio)-1,2,4,5-tetrazine but the reaction using methoxide requires careful control of reaction conditions to avoid formation of the dimethoxy derivative. However, reaction of the bis(methylthio) compound with methyllithium resulted in nucleophilic attack at nitrogen ... 

Oh and co-workers utilized nitrile oxide cycloaddition chemistry for the preparation of 4-oxo-2-alkenylphosphonates 247 by y-acylation of allyhc phosphonates 244 (Scheme 58) [158,159]. Regioselective dipolar cycloaddition between nitrile oxides obtained from nitroalkanes 13 and allylic phosphonates 244 serving as dipolarophiles provided phosphonate-containing 2-isoxazolines 245 in good yields. Isoxazolines 245 upon LDA-mediated ring cleavage followed by hydrolysis of the corresponding oximes 246 yielded 4-oxo-2-alkenylphosphonates 247. 

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>. 

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. 

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. 

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