Aromatic substitution reactions identifying

Spurred by our desire to avoid use of expensive dipolau aprotic solvents in nucleophilic aromatic substitution reactions, we have developed two alternative phase transfer systems, which operate in non-polar solvents such as toluene, chlorobenzene, or dichlorobenzene. Poleu polymers such as PEG are Inexpensive and stable, albeit somewhat inefficient PTC agents for these reactions. N-Alkyl-N, N -Dialkylaminopyridinium salts have been identified as very efficient PTC agents, which are about 100 times more stable to nucleophiles than Bu NBr. The bis-pyridinium salts of this family of catalysts are extremely effective for phase transfer of dianions such as bis-phenolates. 

General. Toluene, chlorobenzene, and o-dichlorobenzene were distilled from calcium hydride prior to use. 4-Dimethylaminopyridine (Aldrich Chemical Co) was recrystalled (EtOAc), and the other 4-dialkylaminopyridines were distilled prior to use. PEG S, PEGM s, PVP s, and crown ethers were obtained from Aldrich Chemical Co., and were used without purification. BuJ r and BU. PBr were recrystallized (toluene). A Varian 3700 VrC interfaced with a Spectraphysics SP-4000 data system was used for VPC analyses. A Dupont Instruments Model 850 HPLC (also interfaced with the SP-4000) was used for LC analyses. All products of nucleophilic aromatic substitution were identified by comparison to authentic material prepared from reaction in DMF or DMAc. Alkali phenolates or thiol ates were pre-formed via reaction of aqueous NaOH or KOH and the requisite phenol or thiophenol in water under nitrogen, followed by azeotropic removal of water with toluene. The salts were transferred to jars under nitrogen, and were dried at 120 under vacuum for 20 hr, and were stored and handled in a nitrogen dry box. 

Another method for sequence analysis is the Sanger N-terminal analysis, based on the use of 2,4-dinitrofluorobenzene (DNFB). When a polypeptide is treated with DNFB in mildly basic solution, a nucleophilic aromatic substitution reaction (SnAt, Section 21.1 lA) takes place involving the free amino group of the N-terminal residue. Subsequent hydrolysis of the polypeptide gives a mixture of amino acids in which the N-terminal amino acid is labeled with a 2,4-dinitrophenyl group. After separating this amino acid from the mixture, it can be identified by comparison with known standards. 

Figure 10.6 summarizes the general ideas presented in Section 10.2. At least four types of energy profiles can exist for individual electrophilic aromatic substitution reactions. Case A is the case of rate-determining generation of the electrophile. It is most readily identified by kinetics. A rate law independent of the concentration of the aromatic is diagnostic of this case. Case B represents rate-determining... 

In the past decade, a wide variety of aromatic substitution reactions has been intensively investigated by applying microreaction technology in conjunction with appropiate process settings to identify routes towards optimized process performance. Enhanced heat and mass transport characteristics achievable in microstruc-tured reactors have been dehberately used to obtain higer product yields, selectivities and purities. Moreover, microreactors have been suceessfuly used to identity synthesis routes towards new products and process conditions which are not attainable in macroscopic bacth processes. 

The following compound has two aromatic rings. Identify which ring is expected to be more reactive toward an electrophilic aromatic substitution reaction. 

Identify the expected directing effects that would be observed if each of the following compounds were to undergo an electrophilic aromatic substitution reaction. 

Domingo (Domingo, et al, 2008) with the pnirpose of identifying the most nucleophilic site of a molecule and assessing the activation/deactivation caused by different substituents on the electrophilic aromatic substitution reactions of aromatic compounds. 

The results in table 2.6 show that the rates of reaction of compounds such as phenol and i-napthol are equal to the encounter rate. This observation is noteworthy because it shows that despite their potentially very high reactivity these compounds do not draw into reaction other electrophiles, and the nitronium ion remains solely effective. These particular instances illustrate an important general principle if by increasing the reactivity of the aromatic reactant in a substitution reaction, a plateau in rate constant for the reaction is achieved which can be identified as the rate constant for encounter of the reacting species, and if further structural modifications of the aromatic in the direction of further increasing its potential reactivity ultimately raise the rate constant above this plateau, then the incursion of a new electrophile must be admitted. 

Now that we ve outlined the general mechanism for electrophilic aromatic substitution we need only identify the specific electrophile m the nitration of benzene to have a fairly clear idea of how the reaction occurs... 

The results of nucleophilic substitutions in solvated ionic aromatic cations (RX+) are strongly dependent on the nature of the halogen and on the solvent cluster size. The energetics of these systems have been studied and it has been shown that the reactions are thermodynamically allowed for each solvent, even for the 1-1 complexes. The observed different behavior related to cluster size is probably governed by kinetic reasons (existence of barriers to the reactions). Two types of substitution reaction have been identified—leading either to X radical or to HX molecule formation. 

The carbocation intermediate of electrophilic aromatic substitution loses a proton to yield the aromatic product. In all cases, a base is involved with proton removal, but the nature of the base varies with the type of substitution reaction. Although this book shows the loss of the proton, it often doesn t show the base responsible for proton removal. This doesn t imply that the proton flies off, unassisted it just means that the base involved has not been identified in the problem. 

Identify the lettered intermediates in the following reaction sequence. When a mixture of ortho and para products results in electrophilic aromatic substitution, consider the para product only. The NMR spectrum of G shows two singlets at 2.6 and 8.18 ppm. 

Fig. 6-7 Rationalization of Photochemical Aromatic Substitution (The brackets identify the less common or unobserved reaction.)...

Heating isoxazole derivatives with aqueous-alkaline permanganate leads to a complete degradation of the heterocycle. With arylisoxa-zoles this results in readily identifiable aromatic acids, from which can be deduced the orientation of electrophilic substitution reactions.104 105 117 Also, the stability of various heterocycles can be compared. Thus, under these reaction conditions, the pyrazole ring is more stable than that of isoxazole (cf. 197-> 198).230... 

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