Ipso nitration

Bromopyrazoles (298) react with fuming nitric acid in 80% sulfuric acid to give 4-nitropyrazoles (ipso nitration Section 4.04.2.3.7). When R was an alkyl group, nitration took place at C-3 giving (299) (a small amount of the dinitro derivative (300) was also obtained) (79AJC1727). Nitrodebromination proceeds from the protonated pyrazolium ion whereas 3-and 5-nitration were expected to involve the free base. 

An ipso attack on the fluorine carbon position of 4-fIuorophenol at -40 °C affords 4-fluoro-4-nitrocyclohexa-2 5-dienone in addtion to 2-nitrophenol The cyclodienone slowly isomenzes to the 2-nitrophenol Although ipso nitration on 4-fluorophenyl acetate furnishes the same cyclodienone the major by-product is 4 fluoro-2,6-dinitrophenol [25] Under similar conditions, 4-fluoroanisole pnmar ily yields the 2-nitro isomer and 6% of the cyclodienone The isolated 2 nitro isomer IS postulated to form by attack of the nitromum ion ipso to the fluorine with concomitant capture of the incipient carbocation by acetic acid Loss of the elements of methyl acetate follows The nitrodienone, being the keto tautomer of the nitrophenol, aromatizes to the isolated product [26] (equation 20) Intramolecular capture of the intermediate carbocation occurs in nitration of 2-(4-fluorophenoxy)-2-methyIpropanoic acid at low temperature to give the spiro products 3 3-di-methyl-8 fluoro 8 nitro-1,4 dioxaspiro[4 5]deca 6,9 dien 2 one and the 10-nitro isomer [2d] (equation 21)... 

L.F. Albright C. Hansen, Eds, Industrial and Laboratory Nitrations , ACS Symposium Series 22, ACS, Washington, DC (1976). Excellent modern review. Ten chapters emphasize various aspects of the chemistry and mechanism of nitrations, including oxidation and ipso-nitration side reactions. Six chapters discuss the chemistry and physical transfer steps between phases. Eight chapters discuss plant operation-improvements, safety features, and new operations. The final chapter is devoted to vapor phase nitrations... 

Likewise, yet in a more pronounced manner, a kaolinite, another clay with a strongly acidic surface (Ho = -3 to -6) (ref. 2), also favors ipso nitration the yield of p-nitroanisole i rises to 27%, boosted by a factor 20 as compared to homogeneous reaction conditions ... 

The proportion of ipso nitration product first depends upon the amount of clay present in the reaction mixture, then reaches a plate. This limit can square wi(- a clay saturation. The results obtained by X-ray diffraction studies on the kaolinite separated from t h e... 

Nitration is widely applicable, can be carried out under a variety of conditions, can usually be stopped cleanly after mononitration, is usually effected by the nitronium ion, can take place on a neutral molecule or a cation, and in many cases can be considered as the standard aromatic electrophilic substitution. However, this last point must be treated with caution. Depending on the reaction conditions and reagents, the mechanism of the reaction does vary, and accompanying reactions such as oxidation (due to the oxidative action of nitric acid), acetoxylation (by acetyl nitrate), and migration of nitro groups following ipso attack (80MI1) can occur. Ipso nitration processes have been extensively studied by Fischer and co-workers. 

Nitro-2-phenylindoles are obtained by electrophilic ipso-nitration of arylazo, hydroxymethyl, and acyl groups on treatment with two equivalents of 70% nitric acid in acetic acid at 25°C. No attack on the phenyl ring is observed under these conditions [80MI1 81JCS(P2)628]. Indolenines undergo nitration mainly at the 5-position (77-85%) (64TL803). 

Ipso-nitration of 4-bromopyrazoles by the sulfuric-nitric acid mixture is approximately 100 times slower than normal nitration of the corresponding unsubstituted pyra-zoles [46], Substitutive nitration of 4-halogeno-l-alkylpyrazoles takes place in parallel with normal nitration at positions 3 and 5 of the heterocycle [46, 74] (Scheme 47). 

Examples of the ipso-nitration of halogen-substituted isothiazoles [387] and thiazoles [388-390] are known. 2,4-Disubstituted 5-bromo- and 5-iodooxazoles react with nitrogen tetroxide to form the 5-nitro derivatives [391],... 

Electron-donating substituents at the C-4 atom direct the incoming nitro group to the position 5 or 7 however, the amount of 7-nitro isomer is higher than that of 4-nitro isomer [222-234], The direction of the nitration of di- and tri-substituted 2,1,3-benzothiadiazoles is determined by the position and electron nature of substituents [223, 227, 229, 230, 232, 235-239], Ipso-nitration of 4,7-dibromo-2,l,3-benzothiadiazole to form 4-bromo-7-nitroderivative has been reported [235],... 

Particularly convenient is the reaction carried out on tetraalkoxytetra-t-butylcalix[4]arenes in which concomitant removal of the f-butyl groups and introduction of four nitro groups occurs (ipso nitration) in 37-67% yield (Scheme 7.13).29... 

Electrophilic attack can also occur at a position already occupied by a substituent, the ipso position. Such ipso substitutions are not common, but they are industrially useful. An example is ipso nitration by... 

Ipso nitration in iodoimidazoles has been reported." Even iodine atoms at C-2 can be replaced in nitric acid, while 4-iodo groups are displaced in nitric-sulfuric acid mixtures. With concentrated nitric acid the trinitro-imidazole 120 is formed (Scheme 29), and this is unexpected in view of the... 

Nitration of a number of 4-substituted toluenes with a formation of ipso-compounds, their transformation and Hammett equation for ipso-nitration was also described [30]. 

Recently Fujiwara and co-workers [16] found that the nitration of A/,VV-diu ethyl-p-toluidine in 70-77% sulphuric acid proceeds by a formation of the o complex through the /pso-attack (on ipso-nitration see p. SO) and after that dte km is rearranged to the nitro compound (2) ... 

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