Amines electrophilic reactions

Pyrimidin-5-amine, 4-methylamino-synthesis, 3, 121 Pyrimidin-5-amine, 4-oxo-purfne synthesis from, 5, 582 Pyrimidinamines acylation, 3, 85 alkylation, 3, 86 basic pXa, 3, 60-61 diazotization, 3, 85 Dimroth rearrangement, 3, 86 electrophilic reactions, 3, 68 Frankland-Kolbe synthesis, 3, 116 hydrolysis, 3, 84 IR spectra, 3, 64 N NMR, 3, 64 nitration, 3, 69 Principal Synthesis, 3, 129 reactivity, 3, 84-88 structure, 3, 67 synthesis, 3, 129 Pyrimidin-2-amines alkylation, 3, 61, 86 basic pK , 3, 60 diazotization, 3, 85 hydrogenation, 3, 75 hydrolysis, 3, 84 mass spectra, 3, 66 Pyrimidin-4-amines acidity, S, 310 alkylation, 3, 61, 86 basic pXa, 3, 61 Schifi base, 3, 85 synthesis, 3, 110, 114 1,3,5-triazines from, 3, 518 Pyrimidin-5-amines basic pXj, 3, 61 hydrogenation, 3, 75 reactions... 

In both cases it may be assumed that the electron-withdrawing effect of both CFgS groups lowers the nucleophilic character of the imide nitrogen to such an extent that it is no longer able to attack—as is the rule with amines—the electrophilic reaction partner (sulfur or carbonyl carbon), but instead forms a weak bond with it. From this intermediate, as is the case with the reactions of CF Cl3 SCl ( = 0, 1, 2), compound CFsSCl and the substitution product can be formed as shown in Scheme 1. 

The previous sections have dealt primarily with reactions in which the new carbon-carbon bond is formed by an SN2 reaction between the nucleophilic carbanions and the alkylating reagent. Another important method for alkylation of carbon involves the addition of a nucleophilic carbon species to an electrophilic multiple bond. The electrophilic reaction partner is typically an a,/i-unsaturated ketone, aldehyde, or ester, but other electron-withdrawing substituents such as nitro, cyano, or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. Other kinds of nucleophiles such as amines, alkoxides, and sulfide anions also react similarly, but we will focus on the carbon-carbon bondforming reactions. 

General Order of Rate Constants. The rate constants of electrophilic reactions of aromatic ligands and their metal complexes fall in the order fo, > kML > kffL. The difference between these rate constants becomes greater as the activity of the attacking reagent decreases. When L is a phenolate, HL is the phenol when L is an amine, HL is the corresponding ammonium derivative. The possible synthetic applications of this sequence can be appreciated from the fact that 8-hydroxyquinoline is usually sulfonated with 15 to 30% oleum, while its copper (II) complex can be readily sulfonated in 70% sulfuric add (5). 

The electrophilic reaction of magnesium cyclopropylidene (113) with Ai-lithioaryl-amines was reported (equation 31) . Thus, electrophilic reaction of magnesium cyclopropylidene (113) derived from 112 with iV-lithio iV-methyl p-anisidine resulted in the formation of a-amino-substituted cyclopropylmagnesium (119) in good yield. Methanol-ysis of the reaction mixture with CH3OD gave a-deuteriated Af-cyclopropyl-Af-methyl-p-anisidine (120) in 82% yield with 98% D-content. 

Solvent-free conditions were used by Tanaka et al. in their assays to obtain intermolecular reactions from alkynes and anilines. The chosen catalyst was [AuMe(PPh3)] with an acidic promoter [92]. Reaction, whose effectiveness was greater in the case of aromatic amines, proceeded via Markovnikov by amine electrophilic attack of the alkyne in a similar way to the methanol addition proposed by Teles (see Section 2.1.3.2) and provided high yields and TONs. 

This type of duality of action is presumably present in other situations, such as the Fries rearrangement (78), the Friedel-Crafts reaction with acid chlorides (65) or acid anhydrides (21), and the catalytic chlorination of nitrobenzene (17). In these reactions it appears that the uncoordinated Lewis acid is the effective catalyst. The same situation is illustrated by recent work on aromatic amination (32, 33) and halogenation (57, 58, 71) and seems to be general feature of Lewis acid-catalyzed electrophilic reactions of aromatic compounds containing suitable donor groups. 

Ring-closing metathesis is well suited for the preparation of five- or six-membered heterocycles, and has also been successfully used to prepare tetrahydropyridines on insoluble supports (Entries 1 and 2, Table 15.23). Because metathesis catalysts (ruthenium or molybdenum carbene complexes) are electrophilic, reactions should be conducted with acylated amines to avoid poisoning of the catalyst. 

Because of their significant electrophilic character, aldehydes are often unstable and will react with nucleophiles. For example, a common reaction of aldehydes is the formation of a hemiaminal with amines. If the amine is a primary amine, the hemiaminal can dehydrate to form an imine as shown in Figure 21. The reaction of aldehydes with primary and secondary amines is a well-studied reaction pathway because it is a common reaction pathway of reducing sugars and amino acids, and this reaction pathway is known as the Maillard reaction (40). In the case of amino acids and sugars, this reaction leads to discoloration, or browning. This reaction will be discussed in greater detail in the Amines-Maillard Reaction section. 

Tetraphenylethylene cyclizes anodically to 9,10-diphenylphenanthrene analogously to its photooxidative cyclization. The attempted anodic cyclization of cis- or frans-stilbene to phenanthrene however failed due to electrophilic reaction of the intermediate radical cation with the solvent 37S Primary aromatic amines are oxidized to radical cations which, depending on the pH of the electrolyte couple to aminodiphenylamines (C-N coupling (84) in Eq. (172) ), yield benzidines (85) at low pH (C-C coupling) or dimerize to hydrazobenzene (86) (N-N coupling) which is subsequently oxidized to azobenzene (Eq. (172) ) 2 5,376,377)... 

The iminium ion, is of course, more electrophilic than the starting amides (amide carbonyl groups are about the least electrophilic of any ), so it gets reduced to the secondary amine. This reaction can be used to make secondary amines, from primary amines and acyl chlorides. 

The cis addition of nitrosyl chloride to cyclic unconjugated polyenes was observed in dichloromethane28. From cyclooctadiene a single diastereomeric dimer 3 (either meso or dl) was produced due to conformational factors associated with the cis configuration. This product underwent transannular electrophilic reaction to give 4. From (Z,Z,Z)-l,5,9-cyclododecatriene the chloro nitroso adduct 5 was obtained as a mixture of the meso and dl forms and was converted to -chloro amine 6 by lithium aluminum hydride/aluminum trichloride reduction 6 was converted to the corresponding aziridine. 13C-NMR spectroscopy was extremely useful in determining the diastereomeric composition of the nitroso dimers. 

We have already mentioned that Dorfman and collaborators have developed a versatile technique to observe ort-lived carbenium ions in solution generated by dissociative pulse radiolysis. This novel approach to the characterisation of transient species has also allowed this schod to measure the rate constants of many electrophilic reactions between carbenium ions (the benzylium ion in particular) and various nucleophiles. In the first paper of the series Jones and Dorfman reported the rate constants of the benzylium ion reaction with methanol, ethanol, the bromide and the iodide ions in ethylene chloride at 24 C. Values of about 5 x 10 sec were obtained for the halide ions and of around 10 sec for the alcohols. Later studies confirmed that the reaction of halide ions vrith benzylium, diphenyl-methylium and triphenylmethylium ions is at the limit of diffusion control. Reaction rate constants of these three carbenium ions with amines and alcdiols were also reported in the same paper. More recently, these studies have been extended to include cyclopropylphenylmetiiylium ion as electrophile, ammonia as nucleophile and methylene chloride and trichloroethane as solvents These results are extremely... 

Different chlorine-substituted fragments in partially substituted complexes have similar reactivities, and the direction of the reaction is not determined by the electron density on the carbon atoms (i.e., their electrophilic properties) but by more specific effects an intramolecular activation via hydrogen bonds in the case of sterically unhindered primary amines and sterical hindrances in the case of secondary and sterically hindered primary amines. The reaction with sterically unhindered primary amines occurs via the route An through the substitution of a halogen atom from an already monofunctionalized fragment. In the case of secondary and sterically hindered primary aliphatic amines, the reaction proceeds via the route Bn with sterically controlled substitution. 

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