Aniline derivatives, also

If only N-substituted aniline derivatives are considered, the IP( 2) value is observed close to that of the parent compound and to vary in a rather narrow range (8.8-9.1 eV). On the other hand, for IPfe) (7.0-7.7 eV) and IP(rtN) (9.5-10.3 eV) larger deviations relative to unsubstituted aniline and greater variation with substitution are found. This can be explained by perturbations of the corresponding benzene MOs by the substituents which is minimal for H2, because it has no coefficients on C-l and N (Cs symmetry). In asymmetric aniline derivatives also JI2 is expected to interact to a substantial extent with n n-... 

Very interesting results were obtained from the reaction of magnesium alkylidene carbenoids with mefa-substituted arylamines (Table 8) . The reaction of magnesium alkylidene carbenoids 157 and 161 with three mefa-substituted anilines was carried out and the results are summarized in Table 8. The reaction of 157 with meta-anisidine gave two products 163 and 164 (in a 30 13 ratio) in 43% yield. The main product was found to have the alkenyl group at the more hindered position (163). As shown in the Table, all the other meto-substituted aniline derivatives also gave the more hindered alkenylated compounds as the main product in variable ratio. 

An example illustrating an approach to a set of substituted aminoindoles employed the starting material 209, which could be annulated to the protected indole 210 in a palladium-catalyzed reaction involving allylamine (Equation 67). The application of cyclic secondary amines as well as aniline derivatives also gave excellent results <2003AGE4257>. An indium-mediated synthesis of ( )-3-alkylideneoxindoles by annulation of related A -(2-iodo-phenyl)-ynamides has also been described <2004OL2825>. 

Under the same conditions, o-iodophenol and aniline derivatives also undergo carbonylative annulation with terminal alkynes in the presence of carbon monoxide to form the corresponding coumarins and 2-quinolines, respectively [80]. This is a particularly interesting discovery because analogous palladiumreactions between a terminal alkyne, o-iodophenol, and CO have previously been reported to afford either aurones or chromones, whereas the corresponding reaction with o-iodoanilines generates six-membered ring 4-quinolines. 

Category Ic cyclizations involve formation of the C3-C3a bond and require aniline derivatives with a nitrogen substituent appropriate for such reaction. Some, but not all, such cyclizations also require an o-substituent, frequently halogen. The rctrosynthetic transformations corresponding to the most important of this group of syntheses are shown in Scheme 4.1... 

Phenazine mono-N-oxides have also been prepared from nitrobenzene derivatives. Condensation of nitrobenzene with aniline using dry NaOH at 120-130 °C results in modest yields of phenazine 5-oxide, although the precise mechanism of this reaction is not well understood (57HC(ll)l) with unsymmetrical substrates it is not possible to predict which of the isomeric fV-oxides will be produced. Nitrosobenzene derivatives also function as a source of phenazine mono-fV-oxides thus, if 4-chloronitrosobenzene is treated with sulfuric acid in acetic acid at 20 °C the fV-oxide is formed (Scheme 21). 

The o-nitrobenzyl and p-nitrobenzyl ethers can b prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also prepared from an alcohol and p-nitrobenzyl alcohol (trifluoroacetic anhydride, 2,6-lutidine, CH2CI2, 67% yield). In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate " 280 nm, 95% yield of nucleotide ). The p-nitrobenzyl ether has been cleaved by electrolytic reduction (—1.1 V, DMF, R4N X, 60% yield) and by reduction with Na2S204 (pH 8-9, 80-95% yield). These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative. ... 

The basic principle of all diazotizations of aromatic amines with a hydroxy- or a sulfonamido group in the 4-position relative to the amino group involves a deprotonation of the OH or NH group, respectively, after diazotization of the amino group. There is also a case of a deprotonation of a CH group in the 4-position of an aniline derivative, namely in the diazotization of 4-aminophenylmalononitrile (2.41) which, by the sequence of steps shown in Scheme 2-23, yields 3-diazo-6-dicyanomethylene-1,4-cyclohexadienone (2.42), as found by Hartzler (1964). This product can also be represented by a zwitterionic carbanion-diazonium mesomeric structure. 

Milner (1992) recently described a novel and versatile modification of the Balz-Schiemann reaction. The amine is diazotized with solid nitrosonium tetrafluoro-borate in CH2C12 and, without isolation, the diazonium salt is heated and yields the fluoroarene in good yield. The method is also applicable to aniline derivatives bearing carboxy and hydroxy substituents, compounds which give poor yields in the classical procedure. 

These reactions involve a diazonium ion (see 12-47) and are much faster than ordinary hydrolysis for benzamide the nitrous acid reaction took place 2.5 x lo times faster than ordinary hydrolysis. Another procedure for difficult cases involves treatment with aqueous sodium peroxide. In still another method, the amide is treated with water and f-BuOK at room temperature. " The strong base removes the proton from 107, thus preventing the reaction marked k j. A kinetic study has been done on the alkaline hydrolyses of A-trifluoroacetyl aniline derivatives. Amide hydrolysis can also be catalyzed by nucleophiles (see p. 427). 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis,Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition metals have also been used. Microwave irradiation has been used to facilitate this reaction. Aniline derivatives react with a-diazoketones, in the presence of a... 

Phthalic anhydride condenses with the aniline derivative in the presence of zinc or aluminum chlorides to yield the intermediate benzoyl-benzoic acid, which subsequently reacts with l,3-bis-V,V-dimethylaniline in acetic anhydride to yield the phthalide. The above compound gives a violet-gray image when applied to a clay developer. Clearly this synthesis is also very flexible and variations in shades of color formers have been obtained by varying the aniline components and also by using phthalic anhydrides substituted, for example, by nitro groups or chlorine atoms. Such products have excellent properties as color formers and have been used commercially. Furthermore, this synthetic route is of great importance for the preparation of heterocyclic substituted phthalides, as will be seen later. 

When aniline derivatives 9-87 bearing an alkyne moiety were used as the reaction input together with an aldehyde and 9-80, furo[2,3-c]quinolines 9-88 were obtained (Scheme 9.18) [58]. Here, an intermediate oxazole is also assumed to occur, enter-... 

Some of the earliest QSAR studies on CYPs were performed by Basak (257), Murray (258), and Marshall (205). Gao et al. (259) explored the influence of electronic parameters of CYP substrates in 1996. The findings of Basak that electronic terms would cancel out have been proven wrong by many research papers published in the following decades. Tyrakowska et al. (260) indicated via QSARs based on calculated molecular orbital descriptors that the cat (maximum velocity converted per nmol of P450 per min) for CYP catalyzed C4-hydroxylation rates of aniline derivatives of different species (rats, rabbit, mice, and human) are closely related to the highest occupied molecular orbital energy (EHOMo)> r - 0-97. Several reviews published by Lewis et al. (212,216,228,261-265) and Ekins (240) should also be mentioned. 

Quantitative stoichiometric gas-solid or solid-solid (these at 0 °C) acylations of amines with acid chlorides are varied (Scheme 32). However, for a clean reaction the liberated hydrochloric acid has to be neutralized by an additional gaseous or solid base that may also be a second mole of the amine. The reactions are performed in an evacuated flask or in a ball-mill, respectively. There are only minimal losses of the amides or sulfonamides upon removal of the stoichiometric coproduct with water [91]. The solid-solid reactions can be turned into sustainable 100% yield processes with optimal atom efficiency by milling stoichiometric 1 1 1 mixtures of acid chloride, aniline derivative, and K2CO3... 

This technique of MEUF has also been successfully employed for the recovery of thuringiensin [258], removal of cresols [262], extraction of chromate anion [257], removal of dissolved organic pollutants [256], removal of -alcohols [263],preconcentration and removal of iron [260], and preconcentration of aniline derivatives [261].Kandori and Schechter [264] have given a detailed account of selecting surfactants for MEUF. The design characteristics of micellar enhanced utrafilters and cross-flow ultrafiltration of micellar surfactant solutions have been described by Markets et al. [265]. 

The palladium catalyzed intramolecular coupling of aryl halides and classical carbanions, sometimes considered a variant of the Buchwald-Hartwig coupling, might also be used for the formation of heterocyclic systems. 7V-(2 -bromophenyl)-propionamides were converted in the presence of the appropriate palladium catalyst and lithium hexamethyldisilazide to oxindoles (3.2.). Under the applied conditions a series of electron deficient and electron rich aniline derivatives, including 2-chloroanilines were transformed successfully.2... 

The combination of the formation of palladium(II) complexes in the oxidative addition of unsaturated halides onto palladium(O), and the palladium(II) mediated ring closure of olefins allows for the elimination of the oxidant. The ring closure of the methallyl-aniline derivative shown in 3.67. in the presence of /J-bromostyrcnc and a catalytic amount of palladium led to the ring closed - coupled product.84 The ring closure might also be accompanied by other follow-up reactions. 2-Methallyl-anilines were converted for example to indolylacetic acid derivatives in the presence of carbon monoxide.85... 

The reduction of aromatic nitro groups by use of electro-generated titanium(III) has also been investigated very intensively, especially in India. Thus, aniline derivatives are generated in high yield Evidently this method has some... 

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