Nitro reaction with amines

Clearly, the tertiaiy nature of the chloride would make an Sn2 mechanism highly unlikely. Furthermore, the nitro substituent is essential to the success of these reactions. Cumyl chloride itself undergoes elimination of HCl on reaction with amines. 

For Ar reactions with amines, the presence of a nitro group in a position ortho to the nucleofuge plays an important role. In spite of the steric effects which will tend to decrease the reactivity of o-nitroaromatics, and the fact that the rate-enhancing effect of the resonance stabilization of the transition state will be more important from the para position, a k°/kp ratio greater than unity is usually found in the reactions of nitroaromatics... 

Aryl- and heteroaryl halides can undergo thermal or transition metal catalyzed substitution reactions with amines. These reactions proceed on insoluble supports under conditions similar to those used in solution. Not only halides, but also thiolates [76], nitro groups [76], sulfinates [77,78], and alcoholates [79] can serve as leaving groups for aromatic nucleophilic substitution. 

The conjugate addition of heteronucleophiles to activated alkenes has been used very often in organic synthesis to prepare compounds with heteroatoms [3 to various activating functional groups, e.g. ketones, esters, nitriles, sulfones, sulfoxides and nitro groups. As in the Michael reaction, a catalytic amount of a weak base is usually used in these reactions (with amines as nucleophiles, no additional base is added). 

Dextran carbamate derivatives. Activation of dextran with 4-nitro-phenyl chloroformate and subsequent reaction with amines leads to the formation of the corresponding carbamate derivatives 2-Hydroxypro-pylamine was selected as a model for amine type drugs. 

The following paragraphs describe the methods of forming azo compounds in which an N-N bond is created (for preparation by coupling see the Section on Preparation of the C-N bond by replacement .) These methods can be classified as (a) oxidative junction of amines (b) oxidation of hydrazo compounds (c) disproportionation of hydrazo compounds (d) action of hypochlorite on iV,jV -diarylsulfamides (e) condensation of nitroso compounds with amines (f) reaction of nitro compounds with amines (g) reduction of nitro and nitroso compounds and (h) reaction of JV-arylhydroxylamines with sulfinylimines. 

Dimethyl-4-methoxy-3-nitro-2-pyri.done, reaction with amines, 832... 

Reduction of a nitro compound to a primary amine. In a 50 ml. round-bottomed or conical flask fitted with a reflux condenser, place 1 g. of the nitro compound and 2 g. of granulated tin. Measure out 10 ml. of concentrated hydrochloric acid and add it in three equal portions to the mixtiue shake thoroughly after each addition. When the vigorous reaction subsides, heat under reflux on a water bath until the nitro compound has completely reacted (20-30 minutes). Shake the reaction mixture from time to time if the nitro compound appears to be very insoluble, add 5 ml. of alcohol. Cool the reaction mixture, and add 20-40 per cent, sodium hydroxide solution imtil the precipitate of tin hydroxide dissolves. Extract the resulting amine from the cooled solution with ether, and remove the ether by distillation. Examine the residue with regard to its solubility in 5 per cent, hydrochloric acid and its reaction with acetyl chloride or benzene-sulphonyl chloride. 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

Nitro alcohols react with amines to form nitro amines. Such a reaction can be carried out with a wide variety of primary and secondary amines, both ahphatic and aromatic a basic catalyst is requited if aromatic amines are involved. The products of reactions between dihydric nitro alcohols and amines are nitrodiamines, many of which are good fungicides (qv). Dihydric nitro alcohols, primary amines, and formaldehyde react to yield nitrohexahydropyrimidines (4). Nitrohexahydropyrimidines can be reduced to the corresponding amines, some of which are good fungicides or bactericides, eg, hexetidine [141-94-6] (5-amino-l,3—bis(2-ethylhexyl)-5-methylhexahydropyrimidine). 

Electrolytic reductions generally caimot compete economically with chemical reductions of nitro compounds to amines, but they have been appHed in some specific reactions, such as the preparation of aminophenols (qv) from aromatic nitro compounds. For example, in the presence of sulfuric acid, cathodic reduction of aromatic nitro compounds with a free para-position leads to -aminophenol [123-30-8] hy rearrangement of the intermediate N-phenyl-hydroxylamine [100-65-2] (61). 

In the reduction of nitro compounds to amines, several of the iatermediate species are stable and under the right conditions, it is possible to stop the reduction at these iatermediate stages and isolate the products (see Figure 1, where R = CgH ). Nitrosoben2ene [586-96-9] C H NO, can be obtained by electrochemical reduction of nitrobenzene [98-95-3]. Phenylhydroxylamine, C H NHOH, is obtained when nitrobenzene reacts with ziac dust and calcium chloride ia an alcohoHc solution. When a similar reaction is carried out with iron or ziac ia an acidic solution, aniline is the reduction product. Hydrazobenzene [122-66-7] formed when nitrobenzene reacts with ziac dust ia an alkaline solution. Azoxybenzene [495-48-7], C22H2QN2O, is... 

Furalazine, Acetylfuratrizine, Panfuran-S. Heating nitrovin in butanol or dimethylformamide at 100—130°C affords furalazine, 6-[2-(5-nitro-2-furanyl)ethenyl]-l,2,4-triazine-3-amine (34). An improved synthesis originates with 5-nitro-2-furancarboxaldehyde and acetone, proceeds through 4-(5-nitro-2-furanyl)-3-buten-2-one followed by a selenium dioxide oxidation to the pymvaldehyde hydrate, and subsequent reaction with aininoguariidine (35). Furalazine, acetylfuratrizine (36), and the A[-A/-bis(hydroxymethyl) derivative, Panfuran-S, formed from the parent compound and formaldehyde (37), are systemic antibacterial agents. 

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). 

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