Tetranitromethane nitration with

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give ct-nitro ketones in 64-96% yield fEqs. 2.42 and 2.43. " The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolydc conphng of the resultant cadon radical of silyl enol ether with NO leads tn ct-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readdy prepared. " ... 

Figure 19.22 Phenolic compounds may be derivatized to contain reactive diazonium groups by nitration with tetranitromethane followed by reduction with sodium dithionite and diazotization with sodium nitrite in dilute HCI.

Nitration with tetranitromethane proceeds along the ion-radical ronte. Tetranitromethane is a smooth nitrating agent and mild oxidizer. It is convenient for nitration of highly activated snbstrates snch as phenols, azulene, and heterocycles in the presence of pyridine, N,iV-dialkylaniline, etc. As shown (Morkovnik 1988), these reactions inclnde one-electron transfer ... 

Tetranitromethane forms with hydrocarbons (such as benzene and toluene) one of the most brisant, destructive mixtures known. TNM is very poisonous, affecting the membranes of the eyes and nose. It is always formed as a by-product in nitration of aromatic hydrocarbons and always accompanies crude TNT (Refs 30 35). 

Villette, J.R., Helbecque, N., Albani, J.R., Sicard, P.J. and Bouquelet, S.J. (1993). Cyclomaltodextrin glucanotransferase from Bacillus circulans E 192 nitration with tetranitromethane. Biotechnology and Applied Biochemistry, 17, 205-216. 

Nitration with tetranitromethane is carried out mostly in the presence of pyridine which with nitroform forms a crystalline addition product. 

Shishkov obtained tetranitromethane by treating nitroform with a mixture of fuming nitric acid with sulphuric acid. Pictet [67] found that tetranitromethane was formed when nitric acid was reacted with acetic acid, or acetyl nitrate with acetic anhydride. 

Phenol nitration with tetranitromethane (37) (TNM) is typically run at pH 8 at room temperature and is selective for tyrosine residues under these conditions (although some oxidation of cysteine residues has been reported) (38). The product of this reaction could be thought to develop through an electrophilic... 

Riordan JF, Vallee BL. Nitration with tetranitromethane. Methods... 

An extensive investigation of photochemical nitrations with tetranitromethane. 

Insolubilization of stem bromelain with carboxymethylcellulose as carrier changes the catalytic behavior of the enzyme against substrates of low and high molecular weight [69-71]. The tyrosyl residues in stem bromelain, which are in an exposed state and hence readily accessible to the solvent, can be acetylated with iV-acetylimidazole at pH 7.5 or nitrated with tetranitromethane at pH 8.0 without change in catalytic activities [72],... 

Price and Radda (338) found that N-acetylimidazole could acetylate up to six tyrosine residues without loss of activity or alteration of Km for substrate however, reaction of about one tyrosine per subunit results in desensitization toward GTP, but the response to ADP is not abolished even by extensive 0-acetylation. Essentially the same results are observed upon nitration with tetranitromethane (TNM). Acetylation does not grossly alter the molecular weight, as measured by sedimentation velocity, or the conformation, as determined by ORD. The GTP site is not protected by NADH alone, but is partially protected (25-50%) by GTP and is at least 75% protected by inclusion of both GTP and NADH in the reaction mixture. Piszkiewicz et al. (339) confirmed these findings by modification with TNM. The reaction is biphasic with initial rapid formation of one residue of 3-nitrotyrosine per subunit. The primary site of reaction is tyrosine-406 in the linear sequence (340). Later (338) the same effect was obtained with chicken GDH with both enzymes there is no influence on activation by ADP. Further, the pH optima of the enzymes are not influenced by the degree of nitration or the inhibition by GTP or activation by ADP (338). 

A long-term, comprehensive investigation of photochemical nitrations with tetranitromethane has produced several new papers in the period under review. The basic mechanism of the reactions involves electron transfer within a charge transfer (CT) complex between the aromatic substrate (ArH) and tetranitromethane, resulting in formation of a radical cation (ArH ), NO2 and the tiinitromethanide anion. 

Riordan J F, Sokolovsky M, Vallee B L (1967). Environmentally sensitive tyrosyl resi-dnes. Nitration with tetranitromethane. Biochem. 6 358-361. 

The preparation of nitromethane at laboratory is the nitration of cyanide acid with mixed acid at 10-30 °C to obtain trinitro acetonitrile, and then trinitromethane after hydrolysis and acidification. You can also obtain trinitromethane salt after treatment of tetranitromethane with basic solution. In industry to produce trinitromethane catalyzed by mercuric nitrate, acetylene is nitrated with fuming nitric acid, and the resulting trinitromethane is dissolved in excess nitric acid, then concentrated sulfuric acid was added trinitromethane is nitrated into tetranitrom-ethane because tetranitromethane is insoluble in acid mixture, trinitromethane and tetranitromethane can be separated [32]. The separated liquid is treated with base to generate trinitromethane salt, and trinitromethane can be produced after acidification. Main reactions mechanism are ... 

The modification of all four tyrosine residues (Tyr-399, 408,449, and 494) of fragment 377-571 by nitration with tetranitromethane yielded a homogeneous derivative which, by circular dichroism and optical rotatory dispersion measurements, had suffered no conformational alterations. Disulfide availability studies, however, indicated a slight increase in the reducibility of its disulfide bonds. The nitrated derivative behaved in an identical manner to unmodified peptide 377-571 in precipitin reactions with antisera to 377-571, and was also equally as effective in inhibiting the precipitin reaction of BSA with antisera to BSA. Also, with each of the antisera tested in immunoadsorbent studies, the derivative... 

The resolution of an a-2,4-dichlorophenoxypropionic acid ester shown in Scheme 2.72 proceeded with very low selectivity when Candida rugosa lipase was used in its native form (E = 1.5). Reductive alkylation of the s-amino groups of lysine residues using pyridoxal phosphate led to only a small improvement. However, when tyrosine residues were nitrated with tetranitromethane, the lipase proved to be highly specific (E = 33). Reduction of the modified nitro-tyrosine lipase with sodium hydrosulfite (which transforms the nitro into an amino group) slightly enhanced the selectivity even further (E = 37). 

The pKa s of the phenolic hydroxyl groups of Tyr 10 and Tyr 21 are closer to the value of the free cunino acid (pK = 10.1), than those of the residues 23 and 35. The higher pK s probably reflect a more hydrophobic environment. The results of nitration with tetranitromethane are also in agreement with a more easy access to Tyr 10 and Tyr 21. However, extensive iodination results in reaction of Tyr 35 as well. In general chemical modification studies do not always seem to be reliable for the distinction between e3q>osed and buried groups and have the possible disadvangtage of introducing structural perturbations. 

The tyrosyl residues of a-lactalbumin from human milk have been nitrated with tetranitromethane three components, which differ in the extent of nitration, were detected. The effect of nitration on the activity of a-lactalbumin in the lactose synthase system was investigated. 

Evidence that stereoelectronic effects are important has been obtained by studying the intramolecular deprotonation selectivity in asymmetric polymethylbenzenes, which is the same in photoinduced SET and in activation by inorganic oxidants, or the methyl vs. iso-propyl selectivity in cymenes. When the benzyl radicals are highly stabilized, they undergo dimerization. More interestingly from the synthetic point of view, these may be used for the photoinduced benzylation of electrophilic alkenes both by using molecular sensitizers such as DCN (1,4-dicyanonaphthalene, see Equation 4.11) and by using titanium dioxide powder photocatalysis, as well as for selective oxidation at the benzylic position " " and photoinduced nitration with tetranitromethane. ... 

In addition to the initial reaction between nitric acid and acetic anhydride, subsequent changes lead to the quantitative formation of tetranitromethane in an equimolar mixture of nitric acid and acetic anhydride this reaction was half completed in 1-2 days. An investigation of the kinetics of this reaction showed it to have an induction period of 2-3 h for the solutions examined ([acetyl nitrate] = 0-7 mol 1 ), after which the rate adopted a form approximately of the first order with a half-life of about a day, close to that observed in the preparative experiment mentioned. In confirmation of this, recent workers have found the half-life of a solution at 25 °C of 0-05 mol 1 of nitric acid to be about 2 days. ... 

The nitric acid used in this work contained 10% of water, which introduced a considerable proportion of acetic acid into the medium. Further dilution of the solvent wnth acetic acid up to a concentration of 50 moles % had no effect on the rate, but the addition of yet more acetic acid decreased the rate, and in the absence of acetic anhydride there was no observed reaction. It was supposed from these results that the adventitious acetic acid would have no effect. The rate coefficients of the nitration diminished rapidly with time in one experiment the value of k was reduced by a factor of 2 in i h. Corrected values were obtained by extrapolation to zero time. The author ascribed the decrease to the conversion of acetyl nitrate into tetranitromethane, but this conversion cannot be the explanation because independent studies agree in concluding that it is too slow ( 5.3.1). 

Nitronaphthalene. 1-Nitronaphthalene is manufactured by nitrating naphthalene with nitric and sulfuric acids at ca 40—50°C (37). The product is obtained in very high yield and contains ca 3—10 wt % 2-nitronaphthalene and traces of dinitronaphthalene the product can be purified by distillation or by recrystaUization from alcohol. 1-Nitronaphthalene is important for the manufacture of 1-naphthalenearnine. Photochemical nitration of naphthalene by tetranitromethane in dichioromethane and acetonitrile to give 1-nitronaphthalene has been described (38). 

---