Salicylate bonds

Salicylate anion is a weaker base than p hydroxybenzoate because it is stabilized by intramolecular hydrogen bonding... 

Methyl salicylate is the methyl ester of o hydroxybenzoic acid Intramolecular (rather than mtermolecular) hydrogen bonding is responsible for its relatively low boiling point... 

Hydrogenation of methyl salicylate gave mostly exs (25) implying that the last double bond to be reduced is often between the two functional groups. Selective esterification of diol (23) with p-bromobenzenesul-phonyIchloride (BsCl) gave (26) which cyclised in strong base. 

Notice from the exampies shown in Figure 11-14 that hydrogen bonds can form between different molecules (for example, H3 N — H2 O ) or between identical molecules (for example, HF—HF). Also notice that molecules can form more than one hydrogen bond (glycine, for example) and that hydrogen bonds can form within a molecule (salicylic acid, for example) as well as between molecules. Example explores the possibilities for hydrogen bond formation. 

Metals may also be linked through an oxygen or nitrogen atom to form a stable metal complex without a carbon-metal bond. These include metal complexes of ethylenediamine tetraacetate (EDTA), diethylenetriamine pentaacetate (DTPA), or ethylenediamine tetramethylphosphonate (EDTMP). Metalloid compounds include antimonyl gluconate and bismuth salicylate. 

Merola reported the preparation of hydrido(carboxylato)iridium(lll) complexes, mer-[lrCl(0C(0)R)(H)(PMe3)3] (90) (R = Ph, Me), by oxidative addition of acetic acid or benzoic acid to [Ir(cod)(PMe3)3]Cl (67) [46]. The structure of 90 (R = Ph) in which the carboxylato ligand coordinates as an T -ligand, was confirmed by X-ray analysis. The reaction of 67 with salicylic acid yielded the product 91, which resulted from activation of the O-H bond of the carboxylato but not of the hydroxo group (Scheme 6-13). 

In addition to the aforementioned types of intermolecular homoconjugates, there are also intramolecular homoconjugates, examples of which we have already mentioned with regard to the titrations of (a) ethylenediamine with acid (p. 248) and (b) of salicylic acid with base (p. 245). This phenomenon of intramolecular hydrogen bonding is usually called chelation, and so the conjugates concerned are preferably designated chelates. 

Chlorogenic acid forms a 1 1 complex with caffeine, which can be crystallized from aqueous alcohol and yields very little free caffeine on extraction with chloroform. Other compounds with which caffeine will complex in this way include isoeugenol, coumarin, indole-acetic acid, and anthocyanidin. The basis for this selection was the requirement for a substituted aromatic ring and a conjugated double bond in forming such a complex. This kind of complex does modify the physiological effects of caffeine.14 Complex formation will also increase the apparent aqueous solubility of caffeine in the presence of alkali benzoates, cinnamates, citrates, and salicylates.9... 

Table 5 shows that the ratio of the excretion rate under hydrous condition to that under anhydrous condition decreases with the decreasing water solubility of the salicylate or with the oil/water distribution coefficient. It can be said that the more water soluble compound is aided to a greater degree by the presence of moisture than those of lesser solubility. This trend is, however, not a direct proportionality due to the influence of other physical phenomena such as viscosity, molecular size, and intermolecular bonding. 

Thanks to the presence of the fluorine substituent on the salicylic ring, the 19F NMR measurements could be performed. Similar values of the chemical shifts for the ligand ( 75.2 ppm) and the complexes (from 70.2 up to — 72.8 ppm) suggested that the fluorine atom was not involved in bonding. 

Examples of reactions involving replacement and cyclization are the long-known preparation of thiophenes (89) from 1,4-diketones, and the formation of l,2-dithiole-3-thione (90) from the salicylate ester analog (91).120 In the latter instance, oxidative cyclization with formation of an S—S bond has occurred this is a common feature of these reactions, particularly if such a link is needed to complete a five-membered ring. Another example of this aspect is afforded by the reaction of the propane-1,3-dione derivatives (92) which yield 3,5-diaryl-1,2-dithiolylium salts (93) when heated with phosphorus pentasulfide in carbon disulfide, followed by perchloric acid.121... 

The reaction of phenylphosphine with boric acid and 2 mol of salicylic aldehyde was carried out in the presence of pyridine with azeotropic removal of water and gave rise to the complex of pyridine with B(III) (116), bonded to three oxygen atoms (87IZV2118 89IZV946) [Eq. (75)]. 

The answer is b. (Hardman, p 1061.) Sulfasalazine consists of sul-fapyridine with 5-aminosalicylic acid linked by an azo- bond. This bond is broken by bacteria that release the salicylic acid, which is believed to be the active agent. Sulfa drugs or salicylic acid used alone is not as effective. The mechanism of action is unknown, but it is believed to be protective action on the mucosa by inhibition of the synthesis of prostaglandins and leukotrienes. 

The reaction of an intramolecularly hydrogen-bonded salicylate ion with a base B is shown in (64) and the two-step mechanism for the reaction is written in Scheme 7. We can show how, according to this mechanism, the... 

The first experimental data for a reaction involving proton transfer from a hydrogen-bonded acid to a series of bases which were chosen to give ApK-values each side of ApK=0 are given in Fig. 15 (Hibbert and Awwal, 1976, 1978 Hibbert, 1981). The results were obtained for proton transfer from 4-(3-nitrophenylazo)salicylate ion to a series of tertiary aliphatic amines in aqueous solution, as in (64) with R = 3-nitrophenylazo. Kinetic measurements were made using the temperature-jump technique with spectrophoto-metric detection to follow reactions with half-lives down to 5 x 10"6s. The reciprocal relaxation time (t ), which is the time constant of the exponential... 

In the two examples of buffer catalysis of proton transfer from an intramolecularly hydrogen-bonded acid which have been discussed, it seems reasonably certain that the mechanism in Scheme 7 applies. The reactions are of the first order with respect to the catalyst B and it therefore follows that proton removal from the non-hydrogen-bonded species is rate-limiting k j > 2[B]- If this step consists of diffusion-controlled proton removal from a low concentration intermediate, the value k2 lx 109dm3 moP s-1 will apply for proton transfer to an amine. In the case of proton removal by hydroxide ion from 4-(3-nitrophenylazo)salicylate ion, the reaction was found to be of the first order in hydroxide ion up to the highest concentrations which could be studied (0.003 mol dm-3) with a rate... 

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