Aniline derivatives, optimization

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... 

To demonstrate the potential of this function of RPS, an experiment was performed. The demonstration as shown in Figure 5 is the separation of a test-mixture of aniline derivatives. The chemical formulas of three aniline derivatives such as aniline,N-methylaniline and N-ethylaniline were input in RPS and the analysis time of 10 min and a resolution value of 1.2 for N-methyl- and N-ethylanilines were requested. RPS provided the predicted retention data of above three compounds both the conditions desired by the user and conditions attained in this system. The system showed that analysis time of 11 min and the resolution of 1.1 would be obtained at the 65 % acetonitrile in the mobile phase and the flow rate of 4 pL/roin. The synthesized chromatogram appeared on the CRT and the printer connected with the computer. The actual run was carried out to evaluate the performance of RPS at that optimized separation condition of 65 % acetonitrile in the mobile phase and the flow rate of 4 pL/min. The system s analysis time of 11 min compares favorably with measured analysis time of 11.5 min. 

Figure 5. Example of the optimization of the separation of aniline derivatives. Input information is underlined. Reproduced with permission from Ref. 9. Copyright 1984, Elsevier.

A relay catalytic hydroamination/redox reaction for the synthesis of cyclic aminals 83 from tertiary amine-substituted 3-en-l-yne derivatives 81 and various aniline derivatives 82 was recently developed by Gong and coworkers (Scheme 12.40) [43]. The gold carbene complex [(IPrlAuNTfj] and TfOH were found to be optimal cocatalysts for this cascade reaction. In their preliminary studies, the authors found that this reaction could be carried out in a highly enantioselective manner, despite that 2 equiv. of an expensive chiral phosphoric acid are required. Interestingly, the diastereoselectivity for a particular substrate appears to be independent of the catalyst or ee. This suggests that the enantioselectivity may result from the ring-closure step, rather than the hydride shift step. 

Much less work has been devoted to optimizing polyester formation. However, diols also react with aromatic diiodides and CO to form polyesters of modest molecular weight (equation 7). Longer reaction times are needed for the much less nucleophilic phenol (compared to the aniline derivatives), which allows more time for chain-limiting side reactions to occur (20). 

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). 

Nakajima et al. (128) found that a number of diamines functioned as moderately effective ligands for Cu(II) in the catalytic aerobic oxidation of 2-naphthols. A series of proline derivatives were evaluated with the aniline ligand 187 providing optimal selectivities. Unfortunately, 2-naphthol affords only racemic binaphthol. With an isolated catalyst, formulated as 187 Cu(OH)Cl in analogy to the known TMEDA Cu(OH)Cl (TMEDA = A,A,A,A-tetramethylethylenediamine), oxidative... 

Well glass plates were loaded with different phosphines, metal complexes, aniline, and 1,3-cyclohexadiene. A coloro-metric assay for unreacted aniline (a red color arising from the acid catalyzed reaction of aniline with furfural) was used to screen successfiil catalysts, that is, those that did not turn red. Catalysts derived from [Pd(7r-allyl)Cl]2 and PPhs were most active. Increasingly, such high-throughput methods are being used in catalyst discovery and optimization. 

The system was first applied for development of chemosensors for gaseous hydrogen chloride. Polyaniline, and its copolymers with different derivates of aniline were used. Then a similar approach was tested in the author s group for optimization of amperometric biosensors for glucose based on electrocatalytical detection of hydrogen peroxide. A pigment Prussian blue was used as an electrocatalyst for decomposition of this product of enzymatic oxidation of... 

After some optimization, it was found that propionyl and acetyl derivatives of anilines can be efficiently arylated under conditions similar to the ones described above (Scheme 9) [50], Electron-rich as well as electron-poor anilides are reactive. Aryl iodides of all electronic properties can be used however, o/f/io-substitution is not tolerated. Propionylanilides are arylated in somewhat higher yields than acetanilides. 

As other double bonded chromophores, the imine chromophore is liable to photochemical E/Z isomerization. The problem has been examined in detail for N-benzylidene aniline and derivatives for both the experimental and computational (TD DFT) point of view. This has given a detailed picture of the effect of substituents on the various steps involved and thus has allowed to predict the best choice of molecules that work as optimal switches , that is are characterized by a well apparent photochromic effect, while maintaining a reasonable thermal stability.High level ab initio calculations have been devoted to the analysis of the isomerization of tZt-penta-3,5-dieniminium cation, a simplified model for the protonated Schiff base of W-cis retinal in rhodopsin. ... 

In general, the A -coupling is relatively easier and can be performed under milder conditions with secondary than with primary amines, mainly due to the fact that iminium ions, derived from secondary amines, are much more electrophilic than their imine counterparts derived from primary amines. Therefore, it is not surprising that this reaction has mainly been optimized for secondary amines and anilines to afford tertiary aUcylpropargylamines and 7V-aryl propargylamines, respectively. There are few examples of the synthesis of... 

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

The structure activity relationship developed for these dihydropyridines showed that optimal activity was derived from BTF, using anilines containing a halogen, cyano or CFj group in the para position and small aliphatic and cyclic ketones and acetophenones. 

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