Nitroacetamidation

Sonication of a chloroform solution containing the alkenes, NaNOz (10 equiv), Ce(NH4)2(N03)6 (2.0 equiv), and acetic acid (12 equiv) in a sealed tube at 25-73 °C provides an excellent way to prepare nitroalkenes. For example, cyclohexene is converted into 1-nitrocyclohexene in 96% yield by this method (Eq. 2.29).56 When the reaction is carried out in acetonitrile, the carbocation intermediates are trapped by acetonitrile to give nitroacetamides in good yield.57 Analogous nitro-acetamidation is possible by using nitronium tetrafluoroborate and acetonitrile (Eq. 2.30).58... 

At lower acidities the iV-nitrobenzamides and /V-methyl-.V-nitrobenzamides have a hydrolysis mechanism that is not acid-catalyzed for these cases plots of log kv - log h2o are linear, as for the acyhmidazoles discussed above. N-Nitroacetamide also hydrolyzes in this way.291 The proposed mechanism is given in Scheme 17, written for TV-nitroacetamide if the hydration shown is a pre-equilibrium (this is a carbonyl compound with a strong electron-withdrawing group attached, so this is likely), only one water molecule will appear in the rate expression (the difference between 3 and 2), as observed.287 Some evidence for hydroxide-catalyzed processes at the very lowest acidities was also found for some of these compounds.287... 

The reaction of l-(2-pyridyl)-3,5-dinitro-2-pyridone 14 with ethyl sodio acetoacetate or diethyl sodio acetone-dicarboxylate gave a mixture of N-(2-pyridyl)nitroacetamide 15, phenol derivatives 16, and a low yield of 2-oxo-2,5-dihydropyrido[1,2-b [ 1,2,4]triazine 4-oxide 17 (79TL1393). The mechanism of the reaction is shown in Scheme 5. 

Dimethyl furoxan-3,4-dicarboxylate was obtained from methoxycarbonylfor-monitrile oxide (96). Treatment of nitroacetamides RR1 NCOCH2NO2 [R, R1 = H, Me Me, Me H, Ph RR1 = (012)4] with SOCI2 afforded furoxan-3,4-dicarboxa-mides (106). 

R = H), and 4-p-nitrophenylpyrimidine (123, R = NO2) by reaction with cyclopentanone, acetophenone, and / -nitroacetophenone, respectively. The yields are, however, quite low (15-30%) and the reaction is found to be applicable to restricted substrates. In some of these reactions A -methyl-a-nitroacetamide could be isolated as the other reaction product. 

The mechanism of this conversion was formulated to occur by an initial addition of the ammonia at position 2 and of the anion of the keto compound (or the enamine) at position 6, i.e., formation of 124. It is of course possible that this addition pattern can be reversed addition of the ammonia at position 6 and of the anion at position 2. In both addition products an internal cyclization occurs by attack of the nitrogen of the amino group on the keto function, yielding the tricyclic intermediate 125. Aromatization occurs by loss of A-methyl-a-nitroacetamide (Scheme III.62). 

Olsen and co-workers used a solution of nitronium tetrafluoroborate in acetonitrile for the V-nitration of acetamides and urethanes at —30°C. The following nitramides were obtained by this method V-nitroacetamide (13 %), V-nitro-2-chloroacetamide (55 %), V-nitro-n-butylacetamide (40 %), V-nitrobenzamide (53 %), ethyl V-nitro-n-butylcarbamate (91 %) and V-nitrosuccinimide (43 %). The low yield of V-nitroacetamide, a primary nitramide, is attributed to competing hydrolysis due to the release of tetrafluoroboric acid as the reaction progresses. The scope of the reaction is improved by moving to more basic solvents like ethyl acetate, 1,4-dioxane and trimethyl phosphate. ... 

From this viewpoint, dinitropyridone 1 and nitropyrimidinone 2 would be supplementary synthetic equivalents of 4 treatable in organic media with considerable safety instead of sodium nitromalonaldehyde. Dinitropyridone 1 is a more suitable substrate for the RTF reaction compared to nitropyrimidinone 2 since the stable nitroacetamide anion is more readily ebminated than anionic urea. 

A plausible mechanism for this reaction is shown in Scheme 8. The nucleophilic attack of the enolate 13 occurs at the 4-position of pyridone 1 to form an adduct intermediate 15, and then regenerated enolate attacks at the 6-position, leading to bicyclic intermediate 16. The order of these nucleophilic attacks is not a serious problem because the same product is obtained even though the 6-position is attacked prior to the 4-position. The following elimination of anionic nitroacetamide from 16 affords RTF product, nitrophenol 14. 

Since simple ketones 22 are less reactive compared to 1,3-dicarbonyl compounds 19, improvement of the nucleophilicity of the a-carbon is required by conversion to enamines. When dinitropyridone 1 is treated with acetone 22a in the presence of amines, 2,6-disubstituted 4-nitroanilines 23a-c are produced in good yields (Table 1). In this reaction, the enamine is formed in situ, and attacks stepwise at the 4- and the 6-position of pyridone 1 to afford bicyclic intermediate from which anionic nitroacetamide is eliminated leading to nitroaniline derivative 23. It is possible to synthesize unsymmetri-cal nitroanilines having different substituents at the 2- and the 6-positions by changing ketones 22, and modification of the amino group is also achieved by using other amines [41]. 

This kind of TCRT is also observed in the reactions of nitropyrimidinone 3 with ketones and methanolic ammonia, which leads to 4,5-disubstituted pyrimidines 26 [44,45]. This reaction is initiated by the successive addition of ammonia and ketone at the 2- and the 6-positions of pyrimidinone 3. The intramolecular cyclization between the amino and the carbonyl groups furnishes bicyclic intermediate 27, and then anionic nitroacetamide is eliminated to afford pyrimidine 26 (Scheme 12). 

The nitration of methyl methacrylate afforded as by-product the nitroacetamide 37 (Scheme 10) <1997J(P1)1559>. Its regiochemistry suggested that the putative ct-carbonyl cation 35, which was then trapped by acetonitrile, may be the intermediate in its formation. However, AMI calculations showed that the tertiary cation 35 may also be in equilibrium with l,2-oxazetidin-2-onyl cation 36, the latter being calculated to be about 1 kcal mol-1 lower in energy. 

There are no significant reports updating the reactivity of substituents attached to ring carbon atoms. To explain the formation of the allylic nitro compound 44 as the major product of the nitration of methyl methacrylate 43 (Scheme 12) versus nitroacetamide 45, a plausible mechanism postulated by Murphy and co-workers... 

Crude reaction product. The material was identified as N-nitroacetamide by infrared analysis but decomposed during attempted purification. 

SYNS 4-ACETAMINO-2-NITROPHENETOLE N-(4-ETHOXY-3-NITRO)PHENYLACETAMIDE N-(4-ETHOXYPHENYL)-3 -NITROACETAMIDE NCI-C01978 2-NITRO-4-ACETAMINOFENETOL (CZECH) 3-NITRO-p-ACETOPHENETIDE 5-NITRO-p-ACETOPHENETIDIDE 3 -NITRO-p-ACETO-PHENETIDIN... 

The structure and the stereochemistry of the 1,2- and 1,4-nitroacetamides were assigned on the basis of spectroscopic analysis and conversion of the 1,2-nitroacetamides to dihydroimidazoles. Variable syn or anti addition was observed depending on the structure of the alkene. Reduction of the nitro group to an amino function by aluminum amalgam allows stereoselective synthesis of vicinal monoacetylated diamines. 

Nitroacetamidation of Phenyl-Substituted Alkenes General Procedures ... 

Reaction with oiefias Olefins (primary, secondary, and tertiary) react with niironium tetrafluoroborate in anhydrous acetonitrile at - 15° to give products which on hydrolysis afford nir-nitroacetamide derivatives in 15-50°/ yield, The reaction is... 

An H acidity function scale has been constructed for methoxide ion in methanol and its mixtures with DMSO (10-80%, v/v) using the dissociation of 11 amides (114) as the anchors for the scale.The degradation pathways of the anti-flammatory and analgesic lomoxicam (115), which contains an amide bond, have been examined recently. In acid, cleavage of the amide bond was the main reaction path and in alkaline and neutral solution the proton shift of the enolic hydroxyl initiated the major degradation pathway. The mechanism of hydrolysis of some A-nitrobenzamides (116) in strong acid follow an -1 mechanism with O-protonation but, in more moderate acid, they exhibit a neutral water-catalysed mechanism. /V-Methyl-/V-nitroacetamide (117) shows only the neutral water-catalysed process. Nitrourea follows an, 4-1 acid-catalysed mechanism. ... 

Distillation of Amm nitroacetamide with coned KOH gives a tribasic acid, C HjNjOj and the Amm salt of this acid gives with Ag nitrate a yel solid which is expl. Another nitro acetamide deriv, C4HjN,Oj, gives with Ag nitrate a wh ctyst compd, AgC H NjO, which expl violently on heating... 

Bloom and coworkers [338] reported in detail the stereochemistry and regiochemistry of the nitroacetamidation of conjugated dienes that were electrolyzed in acetonitrile contain-... 

Variations include the use of 3-alkoxy-enones (i.e. the enol ethers of 1,3-diketones) when the initial Michael-type interaction dictates the regiochemistry Using nitroacetamide instead of cyanoacetamide produces 3-nitro-2-pyridones and using H2NCOCH2C(NH2)=N H2 Cl gives 2-aminopyridine-... 

The iS -alkylation of thio-nitroacetamides with 2-bromo-ketones produces 2-amino-3-nitro-thiophenes. The scheme below shows how the 3,4-bond making involves the intramolecular interaction of the introduced ketone carbonyl with an enamine/thioenol P-carbon. ... 

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