Functionalized amines

Alteration of positional selectivity will result from built-in solvation of the transition state by an adjacent carboxyl-related function.Aminations will be so affected by carboxyl, carboxylate ion, carboalkoxy and less so by carboxamido groups (cf. Section I,D,2,b, structure 12.) Other substitutions such as alkoxylations can be so affected by carboxamido and amidino groups (cf. Section I,D, 2,b, structure 14). The effect of the cyclic hydrogen-bonded form (63) of 2-carboxamidopyridine on the reactivity of a leaving group is not known. 

Functional amines, e.g., m-aminophenol, 2-methyl-2-chloro-3-aminophenol, and 4-chloro-3-aminophenol, react with 4-methoxybut-3-en-2-one to yield functional lepidine derivatives 230 (62AG161). 

The thioacylating properties of phosphonodithioformate 1 were applied to a variety of functionalized amines as shown in Scheme 4. Phosphonothioacylated... 

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

The construction of a tricyclic fused system can also be achieved by one-pot intermolecular/intramolecular cyclocondensations as exemplified by the reaction of functionalized amine 250 with isothiocyanate 251 to give 252 (Equation 33) <2005BMC3185>. 

Addition of organocopper reagents to imine derivatives can readily afford functionalized amine derivatives. Three recent examples are shown below (Equations (129) and (130) Scheme 102).498,498a,498b In these cases, iminium ions are employed as an activated imine. 

In addition to using amine oxidation products as mediators, anodic oxidation reactions can be used to functionalize amine compounds. These reactions include both - examples that generate imines and nitriles, as well as examples that lead to the addition of nucleophiles to the carbon alpha to the nitrogen. 

When the excess of lithium was not filtered off, an over-reduction took place giving functionalized amines 95 in moderated yields (10-45%). ... 

Treatment of Af-phenylazetidine 315 with lithium and a catalytic amount of DTBB (5%) in THF at — 15°C led to a solution of the corresponding y-functionalized organohthium intermediate 316, which by reaction with different electrophiles at temperatures ranging between —78 and 20 °C, and final hydrolysis, afforded the expected functionalized amines 317. The same reaction using azetidine 318 yielded products 320, functionalized at the benzylic position, intermediates 319 being involved in the process (Scheme 93) . ... 

Phenyl-Af-isopropylpyrrolidine (351) was opened with lithium and a catalytic amount (4.5%) of DTBB in THF at room temperature to give the most stable benzylic intermediate 352, which after tandem electrophilic substitution reaction at —78°C and final hydrolysis afforded the expected functionalized amines 353 (Scheme 103). ... 

The reductive ring opening of six-membered nitrogen-containing heterocycles was studied with A-phenyltetrahydroisoquinoline (391). Its lithiation with lithium and a catalytic amount of DTBB (4.5%) afforded the benzylic intermediate 392, which was allowed to react with electrophiles giving, after hydrolysis, functionalized amines 393 (Scheme 110) . It is noteworthy that in the reaction with carbon dioxide, instead of the corresponding lactam, amino acid 393 with X = CO2H was exclusively isolated. 

The different situations of the block copolyampholyte as a function of pH are depicted in Scheme. 1. The same order of deprotonation was observed in copolymers of poly(methacrylic acid) and poly(2-(diethylamino)ethyl methacrylate) [70, 71, 72, 75-77]. In copolymers of poly(methacrylic acid) [78] and poly(2/4-vinylpyridine), on the other hand, deprotonation of the pyridine hydrochloride takes place prior to deprotonation of the carboxyl [79-83] because in comparison to carboxylic functionalities amine hydrochlorides are the weaker acids and vinylpyridinium hydrochlorides the stronger ones. Thus, in the latter systems an isoelectric point (iep) is not observable, while in the first case polyzwitterions are formed which possess the highest amount of charges at that pH resulting in a polyelectrolyte complex (PEC). In the second case polymers with a minimal net charge built the PEC which is stabilized by hydrophobic interactions often accompanied by hydrogen bonding [79, 84-88]. 

Other series of polyamines can be made too. For example, propyl groups can replace some or all of the ethyl groups, or the compound might be modified by reaction with an excess of a monoepoxide to give a hydroxy functional amine. Such modifications are made to improve adhesive properties and sometimes to lower toxicity of the curing agent or make it easier to handle. 

Nitrogen-based nucleophiles continue to remain popular in ring-opening reactions of aziridines. a-Substituted-a-methoxycarbonyl-V-nosylaziridines were opened with a variety of functionalized amines to provide access to enantiopure a,a -disubstituted (3-lactam scaffolds for ditopic peptidomimetics <07OL101>. A related intramolecular regioselective 3,Y-aziridine ring opening with an a-amino functionality was reported in the synthesis of... 

Zirconaaziridines react with unsaturated C-C bonds such as (1) olefins and acetylenes [20], and with unsaturated C-X bonds such as (2) aldehydes and imines [20], (3) heterocumulenes [21,43,49],and (4) carbonates [21,22,43,50] (Scheme 5). The products generated upon workup are a-functionalized amines. Asymmetric transformations can be carried out when a chiral zirconaaziridine or inserting reagent is used optically active allylic amines and amino acid esters have been prepared, and the details of these transformations will be discussed. 

The dynamic thiolester system was subsequently expanded by incorporating three additional thiols in order to probe the performances of the thiol moiety to the target enzyme as well as the enzyme selectivity. Three thiols, 8, 10, and 12, having different adjacent functionalities, amine, sulfonic acid, and amide, respectively, were chosen and added to the dynamic thiolester system. The thiols were chosen due to their solubilities in aqueous media at neutral pH, and also for having similar exchange rates with acetylthiocholine. The kinetic and thermodynamic behavior of thiols/thiolesters are dependent on their structure and functionality,... 

D. NADPH-Dependent Mixed Function Amine Oxidase. 153... 

For the nonlinear step growth case above, eiTg, the crosslink density must be related to p. A relevant model, based on calculating the probabilities of finite chains being formed, has been published For the reaction of A -1- 2B2 (e.g., tetra-functional amine -b difunctional epoxy), A4 is considered to be an effective cross-linking site if three or more of its arms lead out to the infinite network. The probability of finding an effective crosslink is related to one minus the probability of a randomly chosen A leading to the start of a finite chain, which in turn is related to the extent of reaction. Application of this procedure to the system of Fig. 15 has been presented in detail The more complicated reaction of a tetrafunctional amine with a trifunctional epoxy was also considered. ... 

The reaction of disulfides and diselenides with chloramine-T affords N-SR or N —SeR species which are able to undergo addition to alkenes, for example, cyclohexene by an ionic mechanism. After reduction of the cyclohexene adducts, traiw-jS-functionalized amines 1 and 2 were obtained in low yield89. 

---