Amines nucleophilic attack

An alternative approach (Scheme 2) to polyoxyfunctionalised azepines (eg. 9) involves cyclooctatetraene as a starting material via its la, 2a, 5a, 6a -diepoxy-3(3,4(S-diol 7, and subsequent amine nucleophilic attack to give 8 followed by ozonolysis with reductive work up to afford 9 <00TL5483>. 

Mechanism. The neutral amine nucleophile attacks the carbonyl carbon to form a dipolar tetrahedral intermediate. The intramolecular proton transfer from nitrogen and oxygen yields a neutral carbinolamine tetrahedral intermediate. The hydroxyl group is protonated, and the dehydration of the protonated carbinolamine produces an iminium ion and water. Loss of proton to water yields the imine and regenerates the acid catalyst. 

In this procedure the acylating molecule is the active ester formed between the amino acyl moiety and the hydroxy group of HOAt. 40 Compared to the earlier methods utilizing HOSu 41 and HOBt, 42 HOAt maintains the known ability to suppress racemization, but is much more effective in catalyzing peptide-bond formation. This efficiency of HOAt may be attributed to the possible assistance of both N2 and N7 to the amine nucleophilic attack (Scheme 2). If the preferred active ester conformation found in the crystalline state (the heterocyclic At plane lies approximately perpendicular to that of the carboxylic ester moiety)143 is preserved in solution, then assistance to nucleophilic attack on both faces of the ester is likely. 

The most important reaction of this type is the formation of imine bonds and Schiff bases. For example, salicylaldehyde and a variety of primary amines undergo reaction to yield the related imines, which can be used as ligands in the formation of metal complexes. However, it is often more desirable to prepare such metal complexes directly by reaction of the amine and the aldehyde in the presence of the metal ion, rather than preform the imine.113 As shown in Scheme 31, imine formation is a reversible process and isolation of the metal complex results from its stability, which in turn controls the equilibrium. It is possible, and quite likely, that prior coordination of the salicylaldehyde to the metal ion results in activation of the carbonyl carbon to amine nucleophilic attack. But it would be impossible for a precoordinated amine to act as a nucleophile and consequently no kinetic template effect could be involved. Numerous macrocyclic chelate systems have been prepared by means of imine bond formation (see Section 61.1.2.1). In mechanistic terms, the whole multistep process could occur without any geometrical influence on the part of the metal ion, which could merely act to stabilize the macrocycle in complex formation. On the other hand,... 

Just like the reaction with an anhydride, the amine nucleophile attacks the carbonyl carbon. 

The mechanism of the deleterious effects of aldehydes on drug products is generally well understood. For drug substances with primary and secondary amines, nucleophilic attack on the aldehyde produces an a-hydroxyl amine, which can dehydrate to give an imine (Schiff s base) as shown below ... 

Trifluoromethyl-3,l-benzoxazine-4-ones (255) react rapidly with enamines (256) at low temperatures to quinoline-8-carboxylic acids (258) and a secondary amine. Nucleophilic attack of (256) on (255) has been assumed, forming an intermediate vinamidine (257) which immediately undergoes cyclization103 ... 

Hydroxide ion promotes only hydrolysis reactions, not transesterification reactions or aminolysis reactions. Hydroxide ion cannot promote reactions of carboxylic acid derivatives with alcohols or with amines because one function of hydroxide ion is to provide a strong nucleophile for the first step of the reaction. Thus, when the nucleophile is supposed to be an alcohol or an amine, nucleophilic attack by hydroxide ion would form a product different from the product that would be formed from nucleophilic attack by an alcohol or amine. Hydroxide can be used to promote a hydrolysis reaction because the same product is formed, regardless of whether the attacking nucleophile is H2O or HO . 

Amines can be prepared by the alkylation of ammonia. In this array of reactions (Figure 27-2), the amines nucleophilically attack the alkyl halides. As shown below, the first reaction yields a primary amine. Primary amines yield secondary amines which in turn yield tertiary amines, and tertiary amines yield quaternary ammonium salts. 

Soft nucleophiles generally give the best results stabilized enolates such as malonates, or cyanide, are best for carbon-carbon bond formation, but for C-X (X=0, N, S) bond formation the reaction is successful with alkoxides, amines, and thiolates (RS ). In the example below an amine nucleophile attacks the allyl system to generate the more stable product with the double bond within the ring. 

Solvation may also affect leaving group ability so that, for example, fluoride ions are much better solvated in water than in dipolar aprotic solvents. This can affect the nature of the ratedetermining step in the overall reaction. Hence, in the reaction of l-fluoro-2,4-dinitrobenzene with secondary amines, nucleophilic attack is rate limiting in water, but in acetonitrile, base catalysis is observed with the second step rate determining [87, 88]. 

A representation of the addition reaction kinetically equivalent to equation (30), involving the same atoms in the transition state, can be formulated from general base-catalyzed removal of a proton from a free amine nucleophile attacking an already protonated carbonyl compound to yield the transition state shovm in equation (32). Both reactions combine proton transfers with bond making and breaking and the general base-specific acid-catalyzed reaction (equation 32) is"... 

Bruice, P.Y., Bruice, T.C. Intramolecular general base catalyzed hydrolysis and tertiary amine nucleophilic attack vs. general base catalyzed hydrolysis of substituted phenyl quinoline-8- and -6-carboxylates. J. Am. Chem. Soc. 1974, 96(17), 5523-5532. 

Ilvespaa (98) has demonstrated that, using some amines, the 2-chloro-5-nitrothiazole undergoes an opening reaction in a competitive reaction parallel to the normal substitution process. This confirms the sensitivity of position 4 to nucleophilic attack when a nitro group is present in position 5 (Scheme 16). 

Step 1 The amine acts as a nucleophile attacking the carbonyl group and forming a C—N bond... 

Nitrosation of amines is best illustrated by examining what happens when a sec ondary amine reacts with nitrous acid The amine acts as a nucleophile attacking the nitrogen of nitrosyl cation The intermediate that is formed m the first step loses a pro ton to give an N nitroso amine as the isolated product... 

Alkylamines react with leucoquinizarin in a stepwise manner to give l-alh anaino-4-hydroxyanthraquinone, and 1,4-diaLkylamino derivatives after air oxidation. Aromatic amines react similarly in the presence of boric acid as a catalyst. The complex formed (129) causes the less nucleophilic aromatic amines to attack at the 1-, and 4-positions. 

Furazano[3,4-d]pyrimidine, 7-amino-synthesis, 6, 729 UV spectra, 6, 713 Furazanopyrimidines amine synthesis from, 5, 591 synthesis, 6, 418 Furazano[3,4-d]pyrimidines nucleophilic attack, 6, 719 nucleophilic substitution, 6, 713 reduction, 6, 402 7-substituted reactions, 6, 722 Furazano[3,4-a]quinolizines synthesis, 6, 730... 

Ketenes undergo rapid addition by nucleophilic attack at the sp-carbon atom. The reaction of tertiary amines and acyl halides, in the absence of nucleophiles, is a general preparation for ketenes. ... 

The kinetics of the hydrolysis of some imines derived from benzophenone anc primary amines revealed the normal dependence of mechanism on pH with ratedetermining nucleophilic attack at high pH and rate-determining decomposition of the tetrahedral intermediate at low pH. The simple primary amines show a linear correlation between the rate of nucleophilic addition and the basicity of the amine Several diamines which were included in the study, in particular A, B, and C, al showed a positive (more reactive) deviation from the correlation line for the simple amines. Why might these amines be more reactive than predicted on the basis of thei ... 

Sulfonates react with a variety of nucleophiles. Synthesis of M A -bis(trifluoro-methyl)aminotnfluoromethanesulfonate and its reactions with nucleophiles were investigated [33] (equation 31) (Table 13). Nucleophilic attack occurs at either nitrogen or sulfur amines give complex mixtures [33]. Polyfluoroalkyl fluorosul-fates react with amines, alcohols, or alkoxides to yield polyfluoroalkyl sulfamates and dialkyl sulfates, respectively [34] (equation 32) (Table 13). In these reactions. 

The addition of primary amines to fluoroolefins under anhydrous conditions yields imines The hexafluoropropene dimer, perfluoro-2-methyl-2-pcntcne, and ten butylamine react to yield a mixture of two compounds m a 9 4 ratio [4] (equation 3) rather than just the major keteiiimme-imine, as previously reported [5] It IS claimed that this result is possible by means of isomerization to the terminally unsaturated difluoromethylene isomer prior to nucleophilic attack Secondary amines add to fluoroolefins under anhydrous conditions to give fluonnated ternary amines m good yields If the fluoroolefin is added to the amine without cooling the reaction mixture, or if an excess of the secondary armne is used, there is a tendency toward dehvdrofluonnation of the ternary amine The products... 

Nucleophilic ring opening of epoxides by ammonia (Section 16.12) The strained ring of an epoxide is opened on nucleophilic attack by ammonia and amines to give p-amino alcohols. Azide ion also reacts with epoxides the products are p-azido alcohols. 

The formation of 88 is postulated to be occurring by the nucleophilic attack of a hydride ion (47), abstracted from the secondary amine, on the a-carbon atom of the iminium salt (89). The resulting carbonium ion (90) then loses a proton to give the imine (91), which could not be separated because of its instability (4H). In the case of 2-methyIhexamethylenimine, however, the corresponding dehydro compound /l -2-methylazacyclo-heptene (92) was isolated. The hydride addition to the iminium ion occurs from the less hindered exo side. 

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