Nitrite nucleophilic displacement

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Nucleophilic displacement of iodide by the nitrite ion in 1-iodo-17/. l//,2//,2W-perfluoroalkanes affords the 1-nitro analogue (equation 4). Oxidative nitration of the 1-mtro-l//, l//,2//.2//-perfluoroalkane with tetranitromethane yields the ge/n-dinitro compound [4. ... 

With such a diversity of N-nItrosatlon pathways theoretically possible. It Is comforting to note that only a few combinations of circumstances have been Implicated In environmental nitrosamlne formation thus far. Two of these are so facile and prevalent that, as of 20 years ago, they were the only recognized mechanisms of N-nItrosatlon. They Involve the Interaction of di-or trisubstituted ammonia derivatives with a nitrite Ion, as Illustrated In Figure 1 for the secondary amines, under the catalytic Influence of acid. Note the Important special cases of nucleophilic displacement of water from the nitrous acldlum Ion, H20-N0 , by a second nitrite Ion to yield NoOo (as in the reaction at the top of Figure 1), and by nitrate (bottom of Figure... 

Figure 7. Nucleophilic displacement of nitrite from a nitro compound, from...

A nitro group can alternatively be introduced in a sugar by nucleophilic displacement of iodide by a nitrite ion. This procedure was recently used in the preparation of the L-idose derived nitro sugar 14, an intermediate in the synthesis of polyhydroxylated cispentacin analogues (Scheme 6).15... 

Nitroalkanes may be readily prepared by nucleophilic displacement of halide ion by sodium nitrite in DMF or DMSO402. Chiral nitro compounds have been prepared in this way and the reader is directed to a review of these compounds for further details403. 

An alternative and complementary approach, also proceeding via a-nitrooximes, which has been used to generate furoxans of the sugar series but which should be more generally applicable, involves reaction of a-tosyloxy ketones with hydroxylamine hydrochloride in aqueous pyridine followed by treatment of the resulting oximinopyridine salt with sodium nitrite. The latter step is understood to proceed via nucleophilic displacement of the pyridine by nitrite ion, followed by cyclization of the nitrooxime (72CC1117). 

A novel procedure has been developed for the synthesis of phosphate esters of hindered alcohols, and was designed to avoid nucleophilic displacement reactions. It involves photolysis of the alkyl nitrite in the presence of a trialkyl phosphite and proceeds by addition of the alkoxyl radical to phosphorus followed by elimination of an alkyl group (Scheme 3). ... 

A-Oxides, just as in the pyridine series, show a remarkable duality of effect - they encourage both electrophilic substitutions and nucleophilic displacements. The sequence below shows pyridazine A-oxide undergoing first, electrophilic nitration, then, the product, nucleophilic displacement, with nitrite as leaving group. 

Nucleophilic anions, i.e. halides, pseudohalides, alkoxides, phenoxides, and thio-phenoxides, are particularly suitable for these reactions. Even anions of lower reactivity in nucleophilic displacements, i.e. carboxylates, nitrates, nitrites and hydroperoxides, find practical application under PTC conditions. Reactions are rigorously Sf,2 in mechanism primary substrates are thus most suitable, since secondary substrates afford elimination products in high yields, especially when reacted at high temperatures, and tertiary substrates only give rise to elimination. This behaviour is consistent with the low polarity of the organic phase, preventing unimolecular mechanisms and favouring elimination over substitution when the reaction center is not a primary carbon atom. 

The treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

Quite recently, it was reported that heating of tetracyano derivative 268 with potassium nitrite and potassium carbonate in DMF provided 53% of phenoxathiin 270 (Scheme 42) (OOlHl 161). The probable mechanism is, that one activated nitro group in 268 is displaced with a nitrosoxy group by nucleophilic substitution of nitrite ion, followed by hydrolysis to 269, which then undergoes denitrocyclization reaction to the final product. 

Displacement by cyanide works particularly well, and many other nucleophilic substitution reactions are enhanced by PTC. Most monovalent anions can be transferred, including alkoxides, phenoxides, thiocyanates, nitrates, nitrites, superoxides and all of the halides. Divalent anions are usually too hydrophilic to be transferred into the organic phase. 

As discussed above, the nitro groups of tetranitromethane and trinitromethyl compounds are susceptible to nucleophilic attack. Both potassium iodide and alkaline hydrogen peroxide affect the reductive denitration of trinitromethyl groups to em-nitronitronates 1,1,1-trinitroethane (33) is quantitatively reduced to potassium 1,1-dinitroethane (24) on treatment with alkaline hydrogen peroxide. Nucleophiles such as potassium fluoride in DMF can displace nitrite anion from tetranitromethane. Various nucleophiles, including azide, chloride, fluoride and ethoxide have been used to displace one of the nitro groups from fluorotrinitromethane. 

Archibald and co-workers have explored the synthesis of polynitrocyclobutanes and then-derivatives. The synthesis of these compounds via the nucleophilic substitution of cyclobutyl halides with nitrite anion was ruled out at an early stage because displacement in this system is too slow for practical use. This is a consequence of the molecular strain in the cyclobutane ring, which causes carbon atoms to deviate from sp hybridization towards sp character. 

Polyetherimides (PEI) are polyimides containing sufficient ether as well as other flexibi-lizing structural units to impart melt processability by conventional techniques, such as injection molding and extrusion. The commercially available PEI (trade name Ultem) is the polymer synthesized by nucleophilic aromatic substitution between 1,3-bis(4-nitrophthalimido) benzene and the disodium salt of bisphenol A (Eq. 2-209) [Clagett, 1986]. This is the same reaction as that used to synthesize polyethersulfones and polyetherketones (Eq. 2-206) except that nitrite ion is displaced instead of halide. Polymerization is carried out at 80-130°C in a polar solvent (NMP, DMAC). It is also possible to synthesize the same polymer by using the diamine-dianhydride reaction. Everything being equal (cost and availability of pure reactants), the nucleophilic substitution reaction is probably the preferred route due to the more moderate reaction conditions. 

A convenient one-step conversion of moderately activated nitroarenes to phenols was achieved in DMSO via nucleophilic nitrite displacement by the anion of an aldoxime.153 TTie resulting O-arylaldox-ime is rapidly cleaved to the phenol derivative under the reaction conditions. The reaction is also applicable to activated fluorides and even to 2-chloropyridine which, at 110 °C, is converted to 2-pyridone in 72% yield.153 A somewhat related process concerns the synthesis, in 82-92% yield, of 4-alkoxybenzoni-triles (45 R = Me, CH2-oxirane, CHrfh, CHMeCTfcMe from O-alkyl-4-nitrobenzaldoximes (44) via hydride-induced elimination of the alkoxide followed by alkoxy denitration (Scheme 17).154... 

The activation of the co-ordinated ligands towards attack by nucleophiles is also seen in the displacement of nitrite from 8.16 by the very weakly nucleophilic chloride ion (Fig. 8-13). This displacement occurs when the complex is treated with aqueous sodium chloride solution ... 

Figure 8-13. The nitro group in 4-nitroimidazole is activated towards attack by nucleophiles upon co-ordination to cobalt(m). In this case, the very weak nucleophile chloride ion displaces nitrite from 8.16 to give a co-ordinated 4-chloroimidazole ligand.

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