Nitro groups, reactivity

Metronidazole is a nitro-imidazole. It is a mixed amoebicide, i.e. it acts at all sites of infection. It has to be activated in the parasite. By reduction in the amoeba of its nitro group reactive intermediates are formed, resulting in oxidative damage and ultimately cell kill. It is effective against many parasitic intestinal and tissue infections such as trichomoniasis, giardiasis and amoebiasis. It is the drug of choice for amoebic dysentery and amoebic liver abscess. 

The nitrochlorobenzenes are valuable dyestufTs intermediates. The presence of the nitro-groups makes the chlorine atom very reactive and easily replaceable. Treatment with ammonia or dilute alkalis substitutes an amino- or hydroxy-group for the chlorine atom and gives a series of nilroanilines and nilrophenols. 

The nitro-hydrocarbons are neutral substances but when a nitro-group is introduced into a phenol or amine the acidic properties are greatly increased or the basicity decreased. The presence of a nitro-group also tends to make halogen atoms in the same molecule much more reactive. 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

Neither Friedel-Crafts acylation nor alkylation reactions can be earned out on mtroben zene The presence of a strongly deactivating substituent such as a nitro group on an aromatic ring so depresses its reactivity that Friedel-Crafts reactions do not take place Nitrobenzene is so unreactive that it is sometimes used as a solvent m Friedel-Crafts reactions The practical limit for Friedel-Crafts alkylation and acylation reactions is effectively a monohalobenzene An aromatic ring more deactivated than a mono halobenzene cannot be alkylated or acylated under Friedel-Crafts conditions... 

An ortho nitro group exerts a comparable rate enhancing effect m Chloronitrobenzene although much more reactive than chlorobenzene itself is thousands of times less reac tive than either o or p chloronitrobenzene... 

A nitro group behaves the same way m both reactions it attracts electrons Reaction is retarded when electrons flow from the aromatic ring to the attacking species (electrophilic aromatic substitution) Reaction is facilitated when electrons flow from the attacking species to the aromatic ring (nucleophilic aromatic substitution) By being aware of the connection between reactivity and substituent effects you will sharpen your appreciation of how chemical reactions occur... 

I itro-DisplacementPolymerization. The facile nucleophilic displacement of a nitro group on a phthalimide by an oxyanion has been used to prepare polyetherimides by heating bisphenoxides with bisnitrophthalimides (91). For example with 4,4 -dinitro monomers, a polymer with the Ultem backbone is prepared as follows (92). Because of the high reactivity of the nitro phthalimides, the polymerkation can be carried out at temperatures below 75°C. Relative reactivities are nitro compounds over halogens, Ai-aryl imides over A/-alkyl imides, and 3-substituents over 4-substituents. Solvents are usually dipolar aprotic Hquids such as dimethyl sulfoxide, and sometimes an aromatic Hquid is used, in addition. 

Much of the reactivity shown by the ring atoms and substituents of pyrimidine is akin to that of the corresponding parts of 1,3-dinitrobenzene and 3-nitropyridine. This arises from the quantitatively similar electron-withdrawing effects of doubly-bound ring nitrogen atoms and of nitro groups in reducing sharply the aromaticity of the cyclic system. 

In pyrazoles the two most important effects are produced by nitro groups and by quaternization (Section 4.02.3.1.7). Both enhance considerably the reactivity of a second substituent, for example, that of a methyl group towards aldehydes or of a chloro substituent towards amines. 

In the case of nitrobenzene, the electron-withdrawing nitro group is not able to stabilize the positive charge in the complex intermediate. In fact, it strongly destabilizes die intermediate. This destabilization is greatest in the o- and />-intermediates, which place positive charge on the nitrosubstituted caibon. The meta transition state is also destabilized relative to that for benzene, but not as much as the ortho and para transition states. As a result, nitrobenzene is less reactive than benzene, and the product is mainly the meta isomer. 

The striking nucleofugacity of the trimethylammonium leaving group compared with the nitro group in the reaction with fluonde ion is illustrated by the relative reactivities of p-nitrophenyltnmethylammonium perchlorate and p dmi-trobenzene [7J] (Table 4)... 

Secondary steric effects of nitro groups are more easily detected by comparing the reactivities with those of aza derivatives. For example, in structure 20 the rate depression on passing from methyl to -butyl is only 2.5-fold and can be attributed to an inductive effect, whereas in structure 21 a similar change involves the factor 16, which can be attributed in part to steric inhibition of resonance (S.I.R.) of thep-N02 group (reaction with piperidine). 

The A-oxidation of 3-chloropyridazines increases their reactivity toward methoxide and sulfanilamide anions.The reactivity of 4-chloro- or 4-nitro-quinoline and of chloropyridines toward methoxide ion and piperidine is less than that of the corresponding A-oxides (see Tables II and XI, pp. 270 and 338). The activating effect of the A-oxide moiety in 3-halopyridine A-oxides is greater than that of a nitro group, and in fluoroquinoline A-oxides the activation is transmitted to resonance-activated positions in the adjoining rings. 

Nitro and azido. In benzene derivatives, the nitro group is said to rival fluorine and exceed chlorine in replaceability. The reactivity of the nitro group in heterocycles is also very high, and this... 

Greater para than ortho deactivation is seen in the hydrolysis (HCl in AcOH, 100°, 1 hr) of the nitro group in 5,6-diphenyl-2-nitro-3-pyrazinone (218) but not in 6-phenyl- or 3,6-diphenyl-2-nitro-5-pyrazinone (219). Similarly, acid hydrolysis of a 2-bfomo substituent in 3-pyrazinone, but not in 5-pyrazinone, is readily accomplished. All flve of these pyrazinones are stable in strong alkali or alkoxide as a result of complete anionization. Decreased reactivity of... 

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