Phenylacetic acid complexes

Substitution of more complex acids for formic acid in the last step of the purine synthesis will afford intermediates substituted on the imidazole carbon atom. Thus, condensation of diaminouracyl, 12, with phenylacetic acid gives the benzylated... 

Yamase and Goto406 determined first- and second-order rate coefficients for the aluminium chloride-catalysed reaction of halide derivatives of benzoic acid (lO5 = F, 1.73 Cl, 4.49 Br, 4.35 I, 0.81) and phenylacetic acid (105fc2 = F, 12 Cl, 21 Br, 9 I, 6) with benzene. The maxima in the rates for the acid chloride are best accommodated by the assumption that a highly (but not completely) polarised complex takes part in the transition state. Polarisation of such a complex would be aided by electron supply, and consistently, the acetyl halides are about a hundred times as reactive as the benzoyl compounds (see p. 180, also Tables 105 and 108). 

The prophecy on semiochemical systematics in the headline quotation at the start of this chapter remains just that — an intriguing speculation. Some single-component chemosignals do turn up as apparently the main active compound in a complex secretion. In male gerbils (Meriones) one volatile, phenylacetic acid, appears to represent the dominant male state (Thiesen, 1974). Individuality must be added by further components — dietary or variable sebum constituents in this case. Indeed, amongst mammals and some reptiles, complex mixtures seem to be the norm very few taxonomically relevant examples have emerged. 

Aryl methyl ketones have been obtained [4, 5] by a modification of the cobalt-catalysed procedure for the synthesis of aryl carboxylic acids (8.3.1). The cobalt tetracarbonyl anion is converted initially by iodomethane into the methyltetra-carbonyl cobalt complex, which reacts with the haloarene (Scheme 8.13). Carboxylic acids are generally obtained as by-products of the reaction and, in several cases, it is the carboxylic acid which predominates. Unlike the carbonylation of haloarenes to produce exclusively the carboxylic acids [6, 7], the reaction does not need photoinitiation. Replacement of the iodomethane with benzyl bromide leads to aryl benzyl ketones in low yield, e.g. 1-bromonaphthalene produces the benzyl ketone (15%), together with the 1-naphthoic acid (5%), phenylacetic acid (15%), 1,2-diphenylethane (15%), dibenzyl ketone (1%), and 56% unchanged starting material [4,5]. a-Bromomethyl ketones dimerize in the presence of cobalt octacarbonyl and... 

Carbonvlation of Benzyl Halides. Several organometallic reactions involving anionic species in an aqueous-organic two-phase reaction system have been effectively promoted by phase transfer catalysts(34). These include reactions of cobalt and iron complexes. A favorite model reaction is the carbonylation of benzyl halides using the cobalt tetracarbonyl anion catalyst. Numerous examples have appeared in the literature(35) on the preparation of phenylacetic acid using aqueous sodium hydroxide as the base and trialkylammonium salts (Equation 1). These reactions occur at low pressures of carbon monoxide and mild reaction temperatures. Early work on the carbonylation of alkyl halides required the use of sodium amalgam to generate the cobalt tetracarbonyl anion from the cobalt dimer(36). 

There are at least three possibile ways in which the inhibitor can bind to the active site (1) formation of a sulfide bond to a cysteine residue, with elimination of hydrogen bromide [Eq. (10)], (2) formation of a thiol ester bond with a cysteine residue at the active site [Eq. (11)], and (3) formation of a salt between the carboxyl group of the inhibitor and some basic side chain of the enzyme [Eq. (12)]. To distinguish between these three possibilities, the mass numbers of the enzyme and enzyme-inhibitor complex were measured with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI). The mass number of the native AMDase was observed as 24766, which is in good agreement with the calculated value, 24734. An aqueous solution of a-bromo-phenylacetic acid was added to the enzyme solution, and the mass spectrum of the complex was measured after 10 minutes. The peak is observed at mass number 24967. If the inhibitor and the enzyme bind to form a sulfide with elimination of HBr, the mass number should be 24868, which is smaller by about one... 

Methylcryptaustoline iodide (14) was synthesized from phenylacetic acid 47 by Elliott (39) as shown in Scheme 7. Nitration of 47 to the 6-nitro compound 48 and reduction with sodium borohydride afforded lactone 49. Reduction of the aromatic nitro group with iron powder in acetic acid gave ami-nolactone 50, which was converted to tetracyclic lactam 51 with trifluoroacetic acid in dichloromethane. Reduction of the lactam by a borane-THF complex followed by treatment with methyl iodide afforded ( )-0-methylcryptaustoline iodide (14). 

Pd/PPh3 complexes catalyse the carbonylation of activated benzyl alcohols such as 4-hydroxybenzyl alcohol whereas they are inactive in the carbonylation of benzyl alcohol.463 In sharp contrast, the water soluble Pd(tppts)3 complex catalyses the carbonylation of benzyl alcohol to phenylacetic acid, equation (6), under mild reaction conditions employing an aqueous/organic two phase... 

The transition metal-complex-catalyzed carbonylation of benzyl halides to yield phenylacetic acids is an extensively studied reaction [Eq. (7)]. 

The carbonylation of bromobenzene with palladium/tppts complexes was reported by Monteil and Kalck (81). Some of the aforementioned disadvantages were alleviated in a new process for carbonylation of substituted benzyl chlorides (82). The reaction was carried out in a two-phase system in the presence of CO at atmospheric pressure yields of phenylacetic acids of 80-94% were reported. The palladium catalyst contains tppts or BINAS-Na, 10, to allow water solubility. The maximum turnover frequency was found to be 135 h 1, and the lifetime of the catalyst increased as a result of continuous addition of reactants. 

The outcome is more complex in the naphthalene series, where both the position of attack and the competition by rearomatization depend on the reagent chosen and conditions. Monocyanonaphthalenes are benzylated only by />-methoxytoluene, or by m- or />-methoxyphenylacetic acids, not by (poly)methylbenzenes [23,199]. 1,4-Dicyanonaphthalene reacts easily with toluene and a variety of precursors of the benzyl radical (alkylbenzenes [200-205], benzylsilanes, stannanes [206], and borates [56], as well as phenylacetic acids) [207] giving three types of products, viz. l-benzyl-4-cyanonaphthalenes, 1- or 2-benzyl-l,2-dihydro-l,4-dicyanonaphthalenes and dibenzobicyclo[3.3.1]nonanes resulting from the formation of a second carbon-carbon bond (Schs. 12 and 13). 

Oxidation of chiral esters of phenylacetic acids. These esters can be converted into acetates of mandelic esters by oxidation with DDQ in acetic acid. The reaction is diastereoselective when carried out on esters of chiral alcohols, of which 8-phenylmenthol is the most useful. The presence of substituents on the phenyl group has slight effect on the diastereoselectivity, which depends on formation of a donor-acceptor complex between the substrate and the quinone with removal of a hydrogen atom. The acetoxy group then enters from the opposite, more bulky face. 

A Pd-oxazoline complex efficiently converts 3-halochromones into isoflavones in a Miyaura-Suzuki reaction <06T3395>. A one-pot synthesis of 7-hydroxyisoflavones from resorcinol and substituted phenylacetic acids has been described <06TL8161>... 

Hence by evaluating xa from cryoscopic measurements the constancy of Kf. in this formula can be tested. For the system phenylacetic acid 4-nitrobenzene the data in table 26.1 show that is not constant, but that the data are in closer agreement with the assumption of dimer association. However, the figures in table 26.2 show that the equations for dimerisation are not consistent with the behaviour of benzyl alcohol in nitrobenzene, but that in this case is practically constant. This indicates that benzyl alcohol associates in nitrobenzene to form a series of association complexes. 

Dry carbon dioxide gas is bubbled slowly under the surface of a cooled tetrahydrofnran solution of one mole of benzylmagnesium chloride complex until a negative Gilman Schultze color test results. The mixture is then heated to reflux, the addition of carbon dioxide is discontinued, and a further one mole of benzylmagnesium chloride complex is added rapidly (over a period of 20-40 minutes). After completion of addition, the mix is refluxed for 2-4 hours, cooled, and 100-200 mL. of toluene added. The organic solution and suspension is extracted by one 100-mL. portion of water and one 100-mL. portion of 10% sodium carbonate. On acidification of the aqueous extracts, phenylacetic acid is obtained. The organic layer is subjected to distillation to remove solvents and then to vacuum distillation. Dibenzyl ketone and a small amount of tribenzyl carbinol are obtained. 

It is reported that the two-phase carbonylation methodology has been used on a pilot plant scale by Montedison [31 ] for the conversion of benzyl chloride to phenylacetic acid for use in perfume constituents and pesticides (eq. (8)). The carbonylation is run in a biphasic medium employing diphenyl ether and aqueous 40 % sodium hydroxide as solvents. The catalyst system consists of a cobalt carbonyl complex and a benzyltrialkylammonium surfactant. The reaction takes place at low temperature and CO pressure, while benzyl chloride is added continuously to the reaction mixture. 

The possibility of the carbonylation of organic halides under PTC conditions was demonstrated for the first time in 1976 [110], Benzyl chloride was transformed to phenylacetic acid in a xylene/aq. NaOH system containing a Pd° complex and a PT catalyst. Metal carbonyls are the most frequently used carbonylation catalysts. The effectiveness of Co2(CO)g for the PTC carbonylation of benzyl halides was discovered independently by two research groups [111, 112]. Under mild conditions, benzyl halides are converted into carboxylic acids (eq. (8)). 

OH group may be assumed to form the anion/molecule complex 139 which, however, is non-reactive with respect to further tautomerization. Rather, this complex loses the entire carboxylate residue as the fragment ion m/z 255), leaving the phenolic unit as a quinoid neutral fragment (Scheme 37) °. In a further work, 3,4-dihydroxybenzyl carboxylates derived from stearic acid (cf. 140), dihydrocinnamic acid and phenylacetic acid were studied under NC1(NH3)-MS/MS conditions. In these cases, deprotonation was found to take place exclusively at the phenolic sites, owing to the increased acidity of hydroxyl groups in a catechol nucleus, in contrast to simple phenols. Heterolysis of the benzylic C—O bond, e.g. in ions [140 — gives rise to reactive anion/molecule complexes,... 

The hydrophilic palladium complex (2) was also a good catalyst for the carboxylation of benzyl halides under heptane-water two-phase conditions [20]. Benzyl chloride and bromide give phenylacetic acid in high yields under mild conditions (Eq. 5). However, the biphasic carboxylation with PdCI2(PPH,) , is very slow, and gives a considerable amount of benzyl alcohol. The addition of a normal PTC such... 

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