Effect of Tertiary Amines

Effect of Tertiary Amines.—Though the influence of ethereal solvents and additives in anionic polymerizations has been widely investigated, it is only relatively recently that attention has been focussed on the effect of tertiary amines. The complex between Bu Li and tetramethylethylene diamine (TMEDA) is known to be a powerful base readily capable, for example, of abstracting a proton from aromatic hydrocarbons and generating lithiated derivatives. Not surprisingly, therefore, tertiary amines do indeed have significant effects in carboanionic propagations. 

The same complex will induce anionic growth of ethene, and while one research school proposes that the propagating species is a lithium alkyl derivative intimately involving TMEDA, another suggests the action of the base is purely to release monomer Bu Li from its hexameric form in hexane solution, and that this then acts as the initiator. More recent work has established that a Bu Li/TMEDA complex in a 1 1 stoicheiometry is the active species, and that N,A, NW -tetraethylethylenediamine and pentamethyldi-ethylenetriamine are more effective than TMEDA. Furthermore the living polymer obtained has been terminally functionalized by reaction with CO2. 

Perhaps some of the most enlightening results, however, are those reported by Schue and his group.Their n.m.r. spectrum of oligomeric isoprenylithium 

Davidjan, N. Nikolaev, S. Sgonnik, B. Belenki, V. Nesterov, and B. Erussalimsky, Makromol. Chem., 1976, 177, 2469. 

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Nearly all peptide-bond-forming reactions employ tertiary amines in some manner, most commonly for neutralization of amine salts and/or as an adjunct to the activating agent. Table 2 shows the effect of tertiary amine structure on the rate of racemization of two UNCAs in toluene solvent. 

In the absence of base, active esters of both N-alkoxycarbonyl amino acids and N -protected peptides undergo anninolysis with preservation of chiral integrity. There is ample evidence to substantiate this statementP d and no evidence to the contrary. But there is a wealth of accumulated evidence that active esters undergo isomerization when left in the presence of tertiary annine.t In this regard, 4-nitrophenyl esters are much more sensitive than trichlorophenyl esters and piperidino esters are exceptions in that they are unaffected by tertiary anoine.W The isomerization recently observed in the TBTU-mediated couplings of Fmoc-Cys(R )-OH in the presence of 1,2,3-benzotriazol-l-ol in continuous flow solid-phase synthesis is a further example of this phenomenon. The result can be attributed to the effect of tertiary amine on the benzotriazolyl ester that is formed by capture of the acyluronium intermediate before it has time to be aminolyzed. 

A synergistic effect was also found when using a combination of amine and tin catalysts [145]. A much faster reaction occurred between phenyl isocyanate and butanol with mixed tin and tertiary amine catalysts than would be expected from the individual catalyst concentrations. The synergistic effect of tertiary amine on tin catalyst has been confirmed by Wolfe [147] and by Willeboordse et al. [148]. 

Unlike the majority of alcohols discussed in the two preceding Sections, phenols are relatively inert to phosgene even at elevated temperatures [1080]. Yields of the products can be increased, however if a stoicheiometric equivalent of an organic base is used in the reaction [294,846,1358], or if controlled amounts of alkaline solution are added to the reactants in a suitable solvent [36b,1568]. The effect of tertiary amine in the promotion of... 

EFFECT OF TERTIARY AMINE CATALYST ON REACTIVITY OF PHENOL AND ETHYL ALCOHOL WITH PHENYL ISOCYANATE21... 

In this paper, we investigate pH-dependent electron flow control in the presence of the lipophilic tertiary amine dibucaine (2-butoxy-N-(2-(diethylamino)ethyl)-4-quinolinecarboxyamide). Artificial electron acceptors and donors were applied to locate the sites of control in the presence of dibucaine. Furthermore, we studied to what extent the hypothesis of uncoupler-like effects of tertiary amines may be tested by direct measurements of the light-induced proton uptake by thylakoids. 

High molecular weight primary, secondary, and tertiary amines can be employed as extractants for zirconium and hafnium in hydrochloric acid (49—51). With similar aqueous-phase conditions, the selectivity is in the order tertiary > secondary > primary amines. The addition of small amounts of nitric acid increases the separation of zirconium and hafnium but decreases the zirconium yield. Good extraction of zirconium and hafnium from ca 1 Af sulfuric acid has been effected with tertiary amines (52—54), with separation factors of 10 or more. A system of this type, using trioctylarnine in kerosene as the organic solvent, is used by Nippon Mining of Japan in the production of zirconium (55). 

Several articles [7,8] have reported that a persulfate-amine system, particularly persulfate-triethanol amine and persulfate-tetramethylethylenediamine (TMEDA) can be used as redox initiators in aqueous solution polymerization of vinyl monomers. Recently, we studied the effect of various amines on the AAM aqueous solution polymerization and found that not only tertiary amine but also secondary and even primary aliphatic amine and their polyamines can promote the vinyl polymerization as shown in Table 6 [40-42]. 

The effects of a series of added tertiary amines on the rate of chedn scission of other polyesters, including poly( e-caprolactone-co-lactic acid), has been studied and found to be equally great (65). The mechanism with tertiary amines can only be general base catalysis for the effectiveness of the amines was not related to their pK values or lipophilicities. The acceleration of the hydrolysis of the polyesters was used as a strategy for controlling the drug release rate. 

Rosenblatt etal have examined the effect of structure and isotopic substitution upon the permanganate oxidation of some alky famines (Table 4). The isotope effect of 1.84 is considered to be sufficiently low to be compatible with aminium radical-cation formation, and it is felt that, while C-H cleavage is significant for oxidation of primary amines, the dominant mode of oxidation of tertiary amines is electron-transfer, e.g. 

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, facilitates lithiation53 by coordination at the lithium and promoting dissociation of aggregated structures. Kinetic and spectroscopic evidence indicates that in the presence of TMEDA lithiation of methoxybenzene involves the solvated dimeric species (BuLi)2(TMEDA)2.54 The reaction shows an isotope effect for the o-hydrogcn, establishing that proton abstraction is rate determining.55 It is likely that there is a precomplexation between the methoxybenzene and organometallic dimer. 

Interestingly, bases and water have different effect on stability of BENA and intermediate SENA. Additives of tertiary amines stabilize SENAs (191), whereas bases cause spontaneous decomposition of BENAs. SENAs are hydrolytically unstable, whereas BENAs are inert toward water under neutral conditions. 

Oxidation of tertiary amines. Early investigations have shown that tertiary amines are oxidized by C102 to iminium ions, and this oxidation can be used to effect cyclization of 2-aminoethanols or 3-aminopropanols to bicyclic oxazolidines or tetrahydro-l,3-oxazines. 

N-Dealkylation reactions are not restricted to tertiary amines. Secondary amines as well as primary amines can also be dealkylated although both types are less favored than tertiary amines. In the case of primary amines, the lone pair of electrons of the amino group can interact and complex with the Fe3+ of heme. Thus primary amines tend to be inhibitors of P450 activation and for that reason are generally poor substrates. Secondary amines have metabolic properties intermediary between those of tertiary amines and primary amines. They are less-effective inhibitors because of increased steric hindrance to complex formation but are also better substrates because they are less-effective inhibitors and thereby increase the effective concentration of enzyme. 

The two functional groups implicated in a coupling require attention to effect the reaction. The ammonium group of the C02H-substituted component must be converted into a nucleophile by deprotonaton (Figure 1.7). This can be done in situ by the addition of a tertiary amine to the derivative dissolved in the reaction solvent, or by addition of tertiary amine to the derivative in a two-phase system that allows removal of the salts that are soluble in water. The carboxy-containing component is... 

Phenyl carbonochloridate (phenyl chloroformate) effects the dealkylation of tertiary amines A,A-dimethylanilinc yields methyl chloride and the amide 247, and quinuclidine yields the piperidine derivative 248261. 

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