Acetate, as a base

A very recent addition to the already powerful spectrum of microwave Heck chemistry has been the development of a general procedure for carrying out oxidative Heck couplings, that is, the palladium)11)-catalyzed carbon-carbon coupling of arylboronic acids with alkenes using copper(II) acetate as a reoxidant [25], In a 2003 publication (Scheme 6.6), Larhed and coworkers utilized lithium acetate as a base and the polar and aprotic N,N-dimethylformamide as solvent. The coupling... 

According to White [38a], nitrosation involving the use of dinitrogen tetroxide ( nitrogen tetroxide ) represents the most general method of nitrosating amides. The method is quite rapid, yields are high, and purity of products is excellent. Since nitric acid is a coproduct of the reaction, the normal procedure involves the use of an excess of anhydrous sodium acetate as a base. If the base is not added, dinitrosation takes place. 

N (3-Ethynyl phenyl maleimide is synthesized from 3-ethynylaniline and maleic anhydride in DMAc. The cyclodehydration of the resulting amide acid is performed in the usual way with acetic anhydride and nickel acetate as a base catalyst (138). This AB-type monomer has a melting point of 129-131 °C. The polymerization/copolymerization is extremely exotherm (720 J/g) and proceeds in the 180-220 °C temperature range. Furthermore, JV-(3-ethynyl... 

Nakamura disclosed recently a formal [4+2] cycloaddition of pentaarylbromo-fullerene 245 with a large variety of arylalkynes 246 catalyzed by 20 mol% of Cul in the presence of pyridine and sodium acetate as a base (Fig. 65) [338]. The reaction provided fullerene-annulated dihydronaphthalenes 247 in 78-94% yield. 

The Goldberg catalysed Y-arylation of amides gives low yields and requires drastic reaction conditions, but the use of silica-supported copper improves reaction yields. The pyrazolodiazepin system has been A -hetero-arylated in this way using potassium acetate as a base (e.g. equation 4.8) [52]. 

Experimental studies by Davies and coworkers [27] showed that dmba-H reacts with [IrCljCp ] in presence of sodium acetate under mild conditions to form [Ir(q-Cp )(dmba)Cl] as the final cyclometal-lated product. To obsawe the final product, the use of acetate as a base was a must, while the use of other bases such as triethylamine remained unsuccessful. This methodology is also used for the cyclometalation of imines, and similar reactivity is seen with [RhCl Cp ] and [RuCl tp-cymene)] [28]. 

The scope of the synthetic procedure to substituted 1,3-butadienes 16 was later broadened by the same group, with the report of 18 examples of the 1 1 1 coupling of iodoarenes, diarylacetylenes, and monosubstituted alkenes. The mixture Pd(OAc)j, LiQ, and NaHCOj led to the desired products in moderate yields, although minor amounts of the Mizoroki-Heck-type product (ArCH=CHR) were also formed [30]. For the synthesis of 1,3,5-hexatriene derivatives 17, a modification of the former procedure consisting of using silver acetate as a base leads to the 1 2 1 coupling of iodoarenes. 

Applications of thallium bases to other palladium(0)-mediated couplings are rare. A noteworthy example is the use of thallium(i) acetate as a base in Heck coupling to promote the stereoselective synthesis of polyenes though the yields were quite low. Whereas silver acetate was a more effective base to produce J7,i7-polyenes from E-iodides in about 56% yield, it failed in the Heck reaction with Z-iodides since this substrate readily decomposes in the presence of silver acetate. Thallium(i) acetate solved the decomposition problem, however, the product was isolated in poor yield (Scheme 20.20). 

Alkynes have also been used with cesium acetate both for alkynylation and in the synthesis of p)ridines and isoquinolines.The alkynylation of aromatics was promoted by the use of 8-aminoquinoline as a directing group. However, cesium acetate was used in stoichiometric amount in addition to palladium acetate (eq 5). Other insertion reactions have been performed where cesium acetate was used as an additive for nonnatural amino acid synthesis via the addition of a phenyl group during the synthetic route. Also, iodination with palladium acetate and am-ination with a rhodium complex have been successful with cesium acetate as a base. 

C]malonate is sufficient to couple with aryl diazonium salts using aqueous sodium acetate as a base. In the presence of a tautomerizable hydrogen, the azo compound initially formed (e.g., 388) isomerizes to the corresponding hydrazone (e.g., 389). Derivatives of this structural class have been used for the preparation of binuclear heteroaromatic systems. Saponification of the ester groups of hydrazone 389. for example, generated... 

This procedure has been performed in a variety of ways [28 p714, 38-42] with variations in solvent, base and time of reaction. For piperonal conversion, the consensus is toward the use of acetic acid as the solvent, ammonium acetate as the base and 4 hours of reflux time. Dr. Alexander Shulgin, a giant in this field, prefers the use of cyclohexylamine as the base. Strike would not tend to doubt this man s choice, especially since Strike is also getting the... 

Allylation under basic conditions. Allylation can be carried out under basic conditions with allylic acetates and phosphates, and under neutral conditions with carbonates and vinyloxiranes. The allylations under neutral conditions are treated separately in Section 2.2.2.1 from those under basic conditions. However, in some cases, allylations of the same substrates are carried out under both basic and neutral conditions to give similar results. These reactions are treated together in this section for convenience. Allylic acetates are widely used for Pd-catalyzed allylation in the presence of bases tertiary amines or NaH are commonly used[6,7,4l]. As a base, basic alumina or ICF on alumina is conveniently used, because it is easy to remove by filtration after the reaction[42]. Allyl phosphates are more reactive than acetates. The allylation with 40 proceeds stepwise. At first allylic phosphate reacts with malonate and then allylic acetate reacts with amine to give 41(43]. 

Phenols arc highly reactive 0-nucleophiles and allylated easily with allylic carbonates under neutral conditions. EWGs on phenols favor the reac-tion[213]. Allylic acetates are used for the allylation of phenol in the presence of KF-alumina as a base[214]. 

Dimerization is the main path. However, trimerization to form 1.3,6,10-dodecatetraene (15) takes place with certain Pd complexes in the absence of a phosphine ligand. The reaction in benzene at 50 C using 7r-allylpalladium acetate as a catalyst yielded 1,3,6,10-dodecatetraene (15) with a selectivity of 79% at a conversion of 30% based on butadiene in 22 h[ 19,20]. 1,3,7-Octatriene (7) is dimerized to 1,5,7,10.15-hexadecapentaene (16) with 70% selectivity by using bis-rr-allylpalladium. On the other hand. 9-allyl-l,4,6.12-tridecatetraene (17) is formed as the main product when PI13P is added in a 1 1. ratio[21]. 

Carboxylic acids react with butadiene as alkali metal carboxylates. A mixture of isomeric 1- and 3-acetoxyoctadienes (39 and 40) is formed by the reaction of acetic acid[13]. The reaction is very slow in acetic acid alone. It is accelerated by forming acetate by the addition of a base[40]. Addition of an equal amount of triethylamine achieved complete conversion at 80 C after 2 h. AcONa or AcOK also can be used as a base. Trimethylolpropane phosphite (TMPP) completely eliminates the formation of 1,3,7-octatriene, and the acetoxyocta-dienes 39 and 40 are obtained in 81% and 9% yields by using N.N.N M -tetramethyl-l,3-diaminobutane at 50 in a 2 h reaction. These two isomers undergo Pd-catalyzed allylic rearrangement with each other. 

Halogen exchange with KF is not successful ia acetic acid (10). Hydrogen bonding of the acid hydrogen with the fluoride ion was postulated to cause acetate substitution for the haUde however, the products of dissolved KF ia acetic acid are potassium acetate and potassium bifluoride (11). Thus KF acts as a base rather than as a fluorinating agent ia acetic acid. 

Vinyl acetate polymers have long been used as chewing gum bases. They have been studied as controUed release agents for programmed administration of dmgs and as a base for antifouling marine paints (166,167). 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

Practically, the result of reactions (48) and (49) is reaction (50). In reaction (50), we see that acetic acid acts as an acid in the same sense that it does in (48). In either case, it releases hydrogen ions. In (48) acetic acid releases hydrogen ions and forms H+(aq) and in (50) it releases hydrogen ions to NHs and forms NH/. In the same way, ammonia acts as a base in (50) by reacting with the hydrogen ion released by acetic acid. So reaction (50) is an acid-base reaction, though the net reaction does not show H+(aq) explicitly. 

The acetic acid reacts as an acid, giving up its proton, to form acetate, CH3COO-, a substance that can act as a base. We can write (50) in a general form ... 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

Note especially that weak acids do not have strong conjugate bases, as stated in some texts. For example, acetic acid is weak, and its conjugate base, the acetate ion, is certainly not strong. It is even weaker as a base than acetic acid is as an acid. 

Palladium-catalyzed hydroarylation of sterically hindered PTAD adduct 157 with aryl halides in the presence of triphenylarsine, sodium acetate, and DMSO provides a 1 1 mixture of 170 and 171. The same reaction done with sodium fluoride and formic acid provides mixtures containing 171 as the major product. Apparently, the use of sodium fluoride as a base allows the selective formation of the opening products 171 in good yields (Equation 19). Similarly, the 2,3-phthalazine-l,4-dione adduct 172 provides the corresponding products 173 and 174 (Equation 20) <2002AGE3375>. 

It is noteworthy that ZnEt2 has been used as a base in enantioselective allylic substitutions. A remarkable increase in ee was observed when ZnEt2 was used instead of KH, NaH, LiH, LDA, or BuLi in the Pd-catalyzed alkylations of allylic acetates by enolates of malonic esters and related compounds.403 In contrast, application of ZnEt2 was not as very effective as in similar iridium-catalyzed allylic alkylations.404... 

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