Amines as Bases

Amines react as bases with a variety of organic and inorganic acids. 

What acids can be used to protonate an amine Equilibrium favors the products of an acid-base reaction when the weaker acid and base are formed. Because the pA a of many protonated amines is 10-11, the pKi, of the starting acid must be less than 10 for equilibrium to favor the products. Amines are thus readily protonated by strong inorganic acids like HCl and H2SO4, and by carboxylic acids as well. 

Problem 25.21 Draw the products of each acid-base reaction. Indicate whether equilibrium favors the reactants or products. 

The principles used in an extraction procedure were detailed in Section 19.12. 

Because amines are protonated by aqueous acid, they can be separated from other organic compounds by extraction using a separatory funnel. Extraction separates compounds based on solubility differences. When an amine is protonated by aqueous acid, its solubility properties change. 

For example, when cyclohexylamine is treated with aqueous HCl, it is protonated, forming an ammonium salt. Because the ammonium salt is ionic, it is soluble in water, but insoluble in organic solvents. A similar acid-base reaction does not occur with other organic compounds like alcohols, which are much less basic. 

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A variety of catalysts, solvents and amines as base can be employed for the Sonogashira reaction. Typical conditions are, e.g. tetrakis(triphenylphosphine)palladium(0)... 

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

Scheme 4.18 Coupling reaction using amines as base-formation of 2-methyl-indole.

Immobilized Pd(II) pincer complexes were prepared as described previously (20-22). Heck couplings of iodoarenes and acrylates were carried out in DMF using tertiary amines as base and reaction kinetics were monitored as previously reported (20-22). 

In the deuterated 9-methylffuorenyl system (46), Cram and co-workers found retention of configuration in tetrahydrofuran with ammonia or a primary amine as base.127 Streitwieser has obtained similar results with benzyl systems in cyclohexylamine with cyclohexylamide as base.128 Cram s proposed mechanism is shown in Scheme 6. In dimethylsulfoxide, the exchange and racemization... 

Vinylation of allylic alcohols with only a tertiary amine as base is often a very slow reaction in which product (if any) decomposition may be a serious side reaction. Exceptions to this behavior occur when 3-... 

There exists substantial evidence that in reactions that involve oxyanions or amines as bases or as nucleophiles, their partial desolvation, as they enter the transition state, typically has made greater progress than bond formation. In the context of the PNS, this partial loss of solvation represents the early loss of a reactant stabilizing factor and hence reduces the intrinsic rate constant. As discussed at some length in our 1992 chapter,4 for strongly basic oxyanions this desolvation effect often manifests itself in terms of negative deviations from Br Ansted plots and/or in abnormally low p or pnuc values.58,188 In fact, a number of cases have been reported where the pnuc value was close to zero or... 

Corma, A., Iborra, S., Rodriguez, I., Iglesias, M. and Sanchez, F.MCM-41 heterogenized chiral amines as base catalysts for enantioselective Michael reaction, Catal. Lett., 2002, 82, 231-242. 

Benzylcarbonates [119] and carbamates [120] also suffer photosolvolysis. The latter compounds have been extensively investigated in view of their utility for the photoinduced generation of amines (as bases) [121] (see also Sec. 15.5). Intramolecular abstraction by nitro group [122-124] as well as a-cleavage of a-acylbenzylcarbamates [125,126] have also been used for amine liberation (Sch. 5). 

Many reactions become possible only in such superbasic solutions, while others can be carried out under much milder conditions. Only some examples of preparative interest (which depend on the ionization of a C—H or N—H bond) will be mentioned here. The subsequent reaction of the resulting carbanion may involve electrophilic substitution, isomerization, elimination, or condensation [321, 322]. Systematic studies of solvent effects on intrinsic rate constants of proton-transfer reactions between carbon acids and carboxylate ions as well as amines as bases in various dimethyl sulfoxide/ water mixtures have been carried out by Bernasconi et al. [769]. 

Starting material prepared according to ref 108 using Af V-diisobutyl-2,4-dimethylpcntan-3-amine as base. Determined by GC using an internal standard. 

Benzene-1.3,5-triol (phloroglucinol) undergoes reaction with benzofuroxan in methanol with a primary amine as base to give phenazine-l,3-diol 5,10-dioxide.Phenazine-2,3-diol 5,10-dioxides are also synthesized by the reaction of benzene-1,2,4-triol with 6-substituted benzo-furoxans. ... 

Sonogashira coupling of terminal alkynes with aryl or vinyl halides requires a palladium(O) species as catalyst, a copper(I) cocatalyst and an amine as base. 

The above reactions take place in the presence of an organic tertiary amine as base, but in the presence of calcium hydroxide reductive double carbonylation takes place with the formation of ct-hydroxy acids (equation 64). ° To maximize the yield of hydroxy acid it is necessary to use isopropyl alcohol as... 

Heck and Breslow found that alkyl halides, sulfates, and sulfonates undergo carboalkoxylation in the presence of carbon monoxide, an alcohol, a base, and a catalytic amount of sodium cobalt carbonylate, as illustrated for the reaction of 1-iodooctane in methanol with the strongly basic hindered amine dicyclohexylethyl-amine as base. Use of an unhindered amine leads to formation of the amide. 

Later in the book, when we deal with asymmetric enolate reactions, boron enolates will be very important. A simple example20 of an aldol reaction with a boron enolate, prepared from the ester 149 and a boron triflate using an amine as base, shows why. The boron enolate 150 could be prepared with a weak base and reacts with the aldehyde without catalysis to give essentially one diastereoisomer of the aldol 151 in good yield. If the titanium enolate (prepared with TiCI4 and an amine) was used, both the yield and the stereoselectivity were worse. In other circumstances enolates of titanium and other metals are very successful. 

A 1970 patent describes shift catalysis under more forcing conditions (56 atm, 200°C) using a variety of metal salts and organic amines as bases. ... 

Poly (ethylene glycol) (PEG) 4000 has been employed for the preparation of a PEG-anchored version of the previous dichlorotriazine reagents after its reaction with 2,4,6-trichloro[l,3,5]triazine in the presence of NMM [75]. This polymeric reagent (64) has been used for the preparation of anchored benzoic acid derivatives in the presence of NMM and THF as solvent, the supported activated esters being precipitated by addition of ether. Their further reaction with aliphatic and aromatic amines as bases afforded the corresponding amides in good yields, although sec-... 

Normally, as outlined above, the triacidic acid TPPTS was combined with monobasic amines as bases. Dibasic amines such as 1,3-diaminopropane yield highly crosslinked polymeric materials, whereas other diamines such as Than-catCD [(CH3)2NCH2CH2]20 or 3,4,8,9-Bis(dimethylaminomethylene)tricyclode-cane result in the formation of water-soluble ligand salts. 

Insertions of vinylic palladium halides with olefins not conjugated with carbonyl groups is more complex. Rearrangement of the initial insertion product to a i-allyl-palladium derivative usually occurs as in Eq. (p). Since the a -allylic complexes are relatively stable, catalytic reactions to form dienes with tertiary amines as bases are slow and inefficient . A useful catalytic reaction occurs, however, if a nucleophilic secondary amine is used as base instead of the tertiary amine. The a-allylic palladium intermediates are attacked by the amine to form tertiary allylic amines and regenerate the catalyst ... 

Base. Hindered secondary amines that undergo A-alkylation by using this tertiary amine as base can avoid racemization of chirality centers. 

For a general method in CH2CI2 with tertiary amines as base, see Meier et al. (1986). K2CO3 in acetonitrile also seems to be suitable (Koskinen and Munoz, 1990). 

Heck couplings of aryl halides with alkenes in room temperature ionic liquids have been reported [44]. Dialkylimidazolium and n-hexylpyridinium hexafluoro-phosphate and tetrafluoroborate ionic liquids were used as solvents, Pd(OAc)2 and PdCl2 as catalysts, and an amine as base. Addition of ligands such as triphe-nylphosphine, tri-o-tolylphosphine, and triphenylarsine usually had a negative affect on product yield. Addition of cosolvents such as DMF was not necessary. Palladium-catalyzed Heck reactions involving aryl bromides have been performed... 

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