Activation nitro compounds

The diastereoselectivity is observed in the Henry reaction using optical active nitro compounds or a-heteroatom substituted aldehydes. For example, the reaction of O-benzyl-D-lactal-dehyde with methyl 3-nitropropionate in the presence of neutral alumina leads to a mixture of three nitro-aldol products from which D-ribo isomer is isolated by direct crystallization. D-Ribo... 

As would be expected, deuterium exchange between nitromethane and D2O is catalyzed by acetate ions, and the rate of exchange is equal to the rate of bromination under the same conditions (Reitz, 43). Similar correspondences would be expected in the rate of racemization of optically active nitro compounds, but here the position has been complicated by reports (Kuhn and Albrecht, 45 Shriner and Young, 46) that these compounds do not lose their activity completely on conversion to the ion. However, it has recently been shown (Kornblum et al., 47, 48) that the residual activity in these observations was due to the presence of alkyl nitrate as an impurity. The mutarotation of a-nitro camphor represents a similar type of reaction it is catalyzed both by acids and bases (Lowry, 49), and a quantitative study of acid catalysis in chlorobenzene solution has been made (Bell and Sherred, 50). Lowry and most subsequent writers have supposed that the observed change of rotation is due to conversion to the aci-nitro form (II), i.e.,... 

Machetti and co-workers recently reported the dehydration of several activated nitro compounds such as nitroacetone, benzoylnitromethane, ethyl nitroacetate and phenylsidfonylnitromethane on treatment with tertiary diamines (e.g., DABCO, TMEDA) in the presence of dipolaroplules to afford corresponding isoxazoline derivatives directly [94,95]. 

Bartoli G, Latrofa A, Naso F, Todesco PE (1972) Fluorodenitration of some mildly activated nitro-compounds. J Chem Soc Perkin Trans 1 2671... 

Nitromethyl ketones react with p-toluenesulfonic acid (PTSA) in refluxing toluene to give the corresponding furo-xans in 97% yield [20]. When refluxed several hours in xylene or mesitylene in the presence of dipolarophiles and catalytic PTSA, not only activated nitro compounds but also phenylnitromethane and 1-nitropropane afforded the expected isoxazole derivatives, as a result of nitrile oxide cycloadditions [21]. Microwave irradiation in the presence of catalytic PTSA has been successfully applied to condensations between methyl nitroacetate and dipolarophiles [22]. Nitroacetic esters have been converted into the corresponding furoxans with cold sulfuric acid [23], while phenylnitromethane and phenylacetylene in ethereal boron trifluoride etherate are reported to give 3,5-diphenylisoxazole [24]. 

On treatment with stoichiometric TeCLt activated nitro compounds are converted into the corresponding hydroxi-moyl chlorides and the expected isoxazoline is obtained with excess of styrene and triethylamine [38]. Nitroalkanes had been reported previously to be converted into... 

Primary nitro compounds, on base addition, can undergo reactions with dipolarophiles to isoxazole derivatives with loss of water (henceforth called condensations ) only if their acid strength is high enough a screening of many primary nitro compounds indicates that condensation occurs when pATa is lower than 7 (see Table 3 in Ref. [63] and Table 2 in Ref [64]), whereas nitroalkanes carmotbe condensed in these conditions. Those compounds will be indicated hereinafter as active nitro compounds, which include compounds of the type X-CH2-NO2, where X is an EWG as in nitroacetic esters or amides, or in a-nitroketones, or nitroacetonitrile, etc. even phenylnitromethane (pXa 6.8) undergoes condensation with dipolarophiles. However, without addition of a base, condensations in most cases are not observed. 

Condensations of active nitro compounds with electron-poor dipolarophUes slowly occur in water even without base catalysis, as illustrated by the reaction of A-methyl nitroacetamide with acrylamide, which is complete after 26 h. However, the same reaction carried out with addition of 0.1 equiv of base is complete within less than 2h (Figure 8.3) [72]. 

In the course of investigations on the radical addition of activated nitro compounds to unsaturated substrates promoted by Mn(ni) salts, several authors noticed the unexpected formation of isoxazole derivatives as side products. Thus, benzoylnitromethane with phenylacetylene gave 3-benzoyl-5-phenylisoxazole and nitroacetamides such as 14, with 1 -hexene the corresponding 5-butylisoxazolines 15 (Scheme 8.5) [79]. 

In chloroform, activated nitro compounds give condensations with enohzable compounds 22 to isoxazole derivatives, under base catalysis the results are improved with Cu salt in addition to the base (NMP is preferable to DABCO). The 5-methylisoxazole derivatives 23 are obtained selectively, in agreement with the regioselectivities observed in analogous reactions with the parent nitrile oxides or nitronic esters (Scheme 8.7). 

In base catalyzed condensations of active nitro compounds with dipolarophiles in chloroform, furoxans are observed in general as minor by-products, with the noticeable exception of a-nitroketones. The base screening on the model reaction between benzoylnitromethane and styrene in chloroform has shown that, depending on the base employed, the yield of the condensation product is found to be close or considerably lower than the overall conversion of flie dipolarophUe. The missing product corresponds to the furoxan 3 (R = PhCO), which however cannot be detected because it reacts with the dipolarophUe to afford the... 

Evidences gathered so far suggest the possible mechanisms for condensations of activated nitro compounds (iUustrated below). The features of the condensation in chloroform and in water are partly different, thus suggesting that mechanisms could be different too, according to the solvent. 

Excess of activated nitro compound (pATa < 7) ensures the acidity required for the final acid-catalyzed dehydration step. In fact, condensations fail with nitroalkanes and other unactivated nitro compounds with the sole base catalysis. 

In chloroform, as we have seen, the catalytic effect of the base on condensations of activated nitro compounds is related to its H-bonding properties [65]. Unlike the reactions in water, reaction rates increase with the amount of added base, provided an excess of nitro compound ensures the acidify necessary for water release. However, the amount of base is usually maintained within 0.1-0.2 equivalents (with respect to dipolarophile) in order to limit hydrolytic cleavage of the nitro compound. 

Addition of Cu salts to the base allows nitroalkanes to undergo condensations with dipolarophiles it is reasonable to relate this catalytic effect to the known existence of complexes with nitronates [92]. Formation of such complexes might affect conversion of nitro compound into a species prone to cycloaddition and possibly catalyzes cycloaddition. Dehydration to nitrile oxide must be considered, too. In fact, furoxans can be detected in the presence of dipolarophile, while in their absence furoxans can be prepared, at least from nitroacetates or other activated nitro compounds [83]. The Mn nitronate from ethyl nitroacetate has been reported to generate the corresponding nitrile oxide [81]. 

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