Aniline carbonylation

This hipothesis is supported by the following experimental observation when a- or y ZrP was added to a methanol solution of RhCl3 and the suspension was allowed to react for one hour with CO, the resulting filtered dark material tested for aniline carbonylation showed the same catalytic activity. 

In 2012, Mark J. Kurth et al. developed an operationally simple, one-pot, two-step cascade method to afford quinazolino[l,2,3]triazolo[l,4]benzodiazepines 112 (Scheme 4.43) [44]. Fascinatingly, this unique, atom-economical transformation engaged five reactive centers (amide, aniline, carbonyl, azide, and alkyne) and employed environmentally benign iodine as a catalyst. The method seemed to proceed via sequential quinazolinone-forming condensation and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions. The substrate... 

This olionge involves the oxidation of the alcohol grouping of C or C to carbonyl by the action of a second molecule of phenylhydrazine the latter is reduced to aniline and ammonia. Alternative explanations of this reaction have been advanced, but these cannot be discussed here (see, however. Section 111,139,6). 

Reductive carbonylation of nitro compounds is catalyzed by various Pd catalysts. Phenyl isocyanate (93) is produced by the PdCl2-catalyzed reductive carbonylation (deoxygenation) of nitrobenzene with CO, probably via nitrene formation. Extensive studies have been carried out to develop the phosgene-free commercial process for phenyl isocyanate production from nitroben-zene[76]. Effects of various additives such as phenanthroline have been stu-died[77-79]. The co-catalysts of montmorillonite-bipyridylpalladium acetate and Ru3(CO) 2 are used for the reductive carbonylation oLnitroarenes[80,81]. Extensive studies on the reaction in alcohol to form the A -phenylurethane 94 have also been carried out[82-87]. Reaction of nitrobenzene with CO in the presence of aniline affords diphenylurea (95)[88]. 

Both dimethyl carbonate [616-38-6] and diphenyl carbonate [102-09-0] have been used, in place of carbon monoxide, as reagents for the conversion of amines into isocyanates via this route (28,29). Alternatively, aniline [62-53-3] toluene diamines (I JJA), and methylene dianilines (MDA) have also been used as starting materials in the carbonylations to provide a wide variety of isocyanate monomers. 

Conra.d-Limpa.ch-KnorrSynthesis. When a P-keto ester is the carbonyl component of these pathways, two products are possible, and the regiochemistry can be optimized. Aniline reacts with ethyl acetoacetate below 100°C to form 3-anilinocrotonate (14), which is converted to 4-hydroxy-2-methylquinoline [607-67-0] by placing it in a preheated environment at 250°C. If the initial reaction takes place at 160°C, acetoacetanilide (15) forms and can be cyclized with concentrated sulfuric acid to 2-hydroxy-4-methylquinoline [607-66-9] (49). This example of kinetic vs thermodynamic control has been employed in the synthesis of many quinoline derivatives. They are useful as intermediates for the synthesis of chemotherapeutic agents (see Chemotherapeuticsanticancer). 

Carbonyl Iron Powders, General Aniline and Film Corporation, New York, 1962. 

Certain reactions between carbonyl compounds and nucleophiles are catalyzed by amines. Some of these reactions are of importance for forming carbon-carbon bonds, and these are discussed in Chapter 2 of Part B. The mechanistic principle can be illustrated by considering the catalysis of the reaction between aldehydes and hydroxylamine by aniline derivatives. 

When written in this way it is clear what is happening. The mechanisms of these reactions are probably similar, despite the different p values. The distinction is that in Reaction 10 the substituent X is on the substrate, its usual location but in Reaction 15 the substituent changes have been made on the reagent. Thus, electron-withdrawing substituents on the benzoyl chloride render the carbonyl carbon more positive and more susceptible to nucleophilic attack, whereas electron-donating substituents on the aniline increase the electron density on nitrogen, also facilitating nucleophilic attack. The mechanism may be an addition-elimination via a tetrahedral intermediate ... 

The Gassman indole synthesis involves an one-pot process in which hypohalite, a P-carbonyl sulfide derivative 2, and a base are added sequentially to an aniline or a substituted aniline 1 to provide 3-thioalkoxyindoles 3. Raney nickel-mediated desulfurization of 3 then produces the parent indole... 

The mechanism of the indolization of aniline 5 with methylthio-2-propanone 6 is illustrated below. Aniline 5 reacts with f-BuOCl to provide A-chloroaniline 9. This chloroaniline 9 reacts with sulfide 6 to yield azasulfonium salt 10. Deprotonation of the carbon atom adjacent to the sulfur provides the ylide 11. Intramolecular attack of the nucleophilic portion of the ylide 11 in a Sommelet-Hauser type rearrangement produces 12. Proton transfer and re-aromatization leads to 13 after which intramolecular addition of the amine to the carbonyl function generates the carbinolamine 14. Dehydration of 14 by prototropic rearrangement eventually furnishes the indole 8. 

Modification of the Erlenmeyer reaction has been developed using imines of the carbonyl compounds, obtained with aniline," benzylamine or n-butylamine. Ivanova has also shown that an A-methylketimine is an effective reagent in the Erlenmeyer azlactone synthesis. Quantitative yield of 19 is generated by treatment of 3 equivalents of 2-phenyl-5(4ff)-oxazolone (2) (freshly prepared in benzene) with 1 equivalent of iV-methyl-diphenylmethanimine (18) in benzene. Products resulting from aminolysis (20), alkali-catalyzed hydrolysis (21), and alcoholysis (22) were also described. 

We have previously discussed that keto-aldehydes react with anilines first at the aldehyde carbon to form the aldimine. Subsequent condensation with another aniline formed a bis-imine or enamino-imine. The aniline of the ketimine normally cyclizes on the aldimine (24 —> 26). Conversely, cyclization of the aldimine could be forced with minimal aniline migration to the ketimine using PPA (30 —> 31). The use of unsymmetrical ketones has not been thoroughly explored a few examples are cited below. One-pot enamine formation and cyclization occurred when aniline 48 was reacted with dione 49 in the presence of catalytic p-TsOH and heat. Imine formation occurred at the less-hindered ketone, and cyclization with attack on the reactive carbonyl was preferred. ... 

The mechanism is postulated to involve the initial formation of a Schiff base 17 from the condensation of the anilinic amine 16 with the carbonyl-containing substrate. This is followed by a Claisen condensation between the benzylic carbonyl and the activated a-methylene of the imine. ... 

Reaction of the carbonyl group of pi perl done with cyanide and aniline leads to formation of a cyanohydrin-like function known as an oc-aminonitrile (37) hydrolysis under... 

An isoindol1 none moiety forms part of the aromatic moiety of yet another antiinflammatory propionic acid derivative. Carboxylation of the anion from -nitro-ethylbenzene (45) leads directly to the propionic acid (46). Reduction of the nitro group followed by condensation of the resulting aniline (47) with phthalic anhydride affords the corresponding phthalimide (48). Treatment of that intermediate with zinc in acetic acid interestingly results in reduction of only one of the carbonyl groups to afford the isoindolone. There is thus obtained indoprofen (49). ... 

Reduction of anilines containing acid, ester, or carbonyl functions provides a convenient entry to bi- and tricyclic systems, cyclization occurring once the rigidity of the aromatic ring has been lost through saturation (1,2,61,77). 

The well-known photopolymerization of acrylic monomers usually involves a charge transfer system with carbonyl compound as an acceptor and aliphatic tertiary amine, triethylamine (TEA), as a donor. Instead of tertiary amine such as TEA or DMT, Li et al. [89] investigated the photopolymerization of AN in the presence of benzophenone (BP) and aniline (A) or N-methylaniline (NMA) and found that the BP-A or BP-NMA system will give a higher rate of polymerization than that of the well-known system BP-TEA. Still, we know that secondary aromatic amine would be deprotonated of the H-atom mostly on the N-atom so we proposed the mechanism as follows ... 

The end group of the polymers, photoinitiated with aromatic amine with or without the presence of carbonyl compound BP, has been detected with absorption spectrophotometry and fluororescence spectrophotometry [90]. The spectra showed the presence of tertiary amino end group in the polymers initiated with secondary amine such as NMA and the presence of secondary amino end group in the polymers initiated with primary amine such as aniline. These results show that the amino radicals, formed through the deprotonation of the aminium radical in the active state of the exciplex from the primary or secondary aromatic amine molecule, are responsible for the initiation of the polymerization. 

However, this oxidation to carbonyl failed with the complexes of tetralin, o-chlorotoluene, 9,10-dihydrophenanthrene, and acenaphthalene [109]. The aniline complex can be oxidized to the nitrobenzene complex using H202 in CF3C02H [86] Eq. (38). This reaction parallels the analogous oxidation of aminocobaltici-nium [86, 111],... 

Meerwein reactions can conveniently be used for syntheses of intermediates which can be cyclized to heterocyclic compounds, if an appropriate heteroatom substituent is present in the 2-position of the aniline derivative used for diazotization. For instance, Raucher and Koolpe (1983) described an elegant method for the synthesis of a variety of substituted indoles via the Meerwein arylation of vinyl acetate, vinyl bromide, or 2-acetoxy-l-alkenes with arenediazonium salts derived from 2-nitroani-line (Scheme 10-46). In the Meerwein reaction one obtains a mixture of the usual arylation/HCl-addition product (10.9) and the carbonyl compound 10.10, i. e., the product of hydrolysis of 10.9. For the subsequent reductive cyclization to the indole (10.11) the mixture of 10.9 and 10.10 can be treated with any of a variety of reducing agents, preferably Fe/HOAc. 

For the synthesis of quinolines and isoquinolines the classical approaches are the Skraup and the Bischler-Napieralski reactions. The reaction of substituted anilines with different carbonyl compounds in acid medium has been reported to be accelerated under microwave irradiation to give differently substituted quinolines and dihydro quinolines [137]. Although the yields are much better and the conditions are milder than under conventional heating, the acidity of the medium may prevent the preparation of acid-sensitive compounds. Thus, alternative approaches have been investigated. Substituted anilines and alkyl vinyl ketones reacted under microwave irradiation on the surface of sihca gel doped with InCU without solvent [137] to furnish good yields of quinohnes 213 (Scheme 77). 

B (hydrogen-bond acceptor) unit, as it is also present in many of the derivatives that are not sweet. Its presence in these derivatives promotes the cis orientation of the amide (or thioamide) bond formed with the aniline amino group, as it is known, from infrared and n.m.r. studies, that a bulky substituent on an amide (or thioamide) favors the cis orientation, owing to the steric interaction between the bulky group and the carbonyl oxygen atom. Such an arrangement will bring the AH,B system into the correct spatial separation from the D unit. 

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