Amination of aromatic rings

Direct amination of aromatic rings 1-25 Aminoalkylation of aromatic rings 1-32 Rearrangement of N-nitroamines 1-33 Rearrangement of N-nitrosoamines... 

Intramolecular radical reactions are more efficient Palladium-catalysed amination of aromatic rings 1092... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Reactions 11-15-11-18 are direct formylations of the ring. Reaction 11-14 has not been used for formylation, since neither formic anhydride nor formyl chloride is stable at ordinary temperatures. Formyl chloride has been shown to be stable in chloroform solution for 1 h at -60°C, but it is not useful for formylating aromatic rings under these conditions. Formic anhydride has been prepared in solution, but has not been isolated.Mixed anhydrides of formic and other acids are known and can be used to formylate amines (see 10-56) and alcohols, but no formylation takes place when they are applied to aromatic rings. See 13-15 for a nucleophilic method for the formylation of aromatic rings. 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

Reduction of aromatic rings with lithium or calcium " in amines (instead of ammonia—called Benkeser reduction) proceeds further and cyclohexenes are obtained. It is thus possible to reduce a benzene ring, by proper choice of reagent, so that one, two, or all three double bonds are reduced. Lithium triethylborohy-dride (LiBEtsH) has also been used, to reduce pyridine derivatives to piperidine derivatives." ... 

Inspired by the results of aromatic-ring hydroxylation from the laboratory of Karlin and co-workers, a few groups provided further examples of such reactivity, including some structurally characterized complexes of modified m-xylyl-based pyridine-donor ligands (Schiff base and non-Schiff base acyclic ligands), as well as aliphatic amine donor ligands (179) (Cu-Cu 2.990 A),169 (180) (Cu-Cu 3.015 A),170 and (181) (Cu-Cu 2.999 A).171 172 A m-xylyl-based ligand system that was used by Mukherjee and co-workers in the formation of complex (181) also resulted in the isolation of a bis(/i-hydroxo)dicopper(II) complex (182) (Cu-Cu 3.004 A).171,172 Casella and co-workers demonstrated that when their dicopper(I) complex... 

We have now adjusted our molecular systems to provide a model in which both forces can operate simultaneously. The U-shaped relationship that exists between the imide function and amides of aryl amines creates a hydrogen bonding edge and a planar stacking surface that converge from perpendicular directions as in 44 to provide a microenvironment complementary to nucleic acid components. A large number of aromatic rings can be functionalized with this simple scaffold, and spacers (R) can also be incorporated. The imide function is a mimic of the thymine residues. 

One of the early examples of pharmacophore modeling of the ala- and aib-AR subtypes was carried out by means of the Apex-3D software [100]. The common features of the pharmacophore models of the two arAR subtypes were a protonated amine, an aromatic ring and a polar region. The main difference between the two pharmacophores was the distance between the aromatic ring and the amine function. 

Relative configuration of aromatic ring and amine. (R)-(-)-form. 

Reduction of aromatic rings with lithium340 or calcium341 in amines (instead of ammonia)... 

In aliphatic secondary amines the N—H bending band is usually absent from the spectrum or else it is very weak and appears at 1650-1550 cm - x. In aromatic secondary amines the band is of medium intensity, and appears in the same region, but the assignment is complicated by the presence of aromatic ring vibrations which also occur here, and which are sometimes intensified when a nitrogen atom is attached to the ring. 

Birch reduction11 is the partial reduction of aromatic rings by solvated electrons produced when alkali metals dissolve (and react) in liquid amines. Typical conditions are sodium in liquid ammonia or lithium in methylamine. These electrons add to benzene rings to produce, probably, a dianion 57 that is immediately protonated by a weak acid (usually a tertiary alcohol) present in solution. The anions in the supposed intermediate 57 keep as far from each other as they can so the final product is the non-conjugated diene 58. It is important to use the blue solution of solvated electrons before it reacts to give hydrogen and NaNH2. 

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