Of p-aminobenzoic acid

White crystals, m.p. 90-9 rC. Prepared fromp-nitrotoluene by way of p-aminobenzoic acid. It is used as a local anaesthetic on mucous surfaces internally and by injection, and is taken internally to relieve gastric pain. 

Ethyl p-aminobenzoate (esterification of p-aminobenzoic acid). Place 80 ml. of absolute ethyl alcohol in a 250 ml. conical flask equipped with a two-holed cork and wash-bottle tubes. Pass dry hydrogen chloride (Section 11,48,2) through the alcohol until saturated—the increase in weight is about 20 g.—and transfer the solution to a 250 ml. round-bottomed flask. Introduce 12 g. of p-aminobenzoic acid, fit a double surface condenser to the flask, and reflux the mixture for 2 hours. Upon... 

A chance observation made some time prior to the full structural elucidation of cocaine in fact led to one of the more important lasses of local anesthetics. It was found that the simple ethyl e. ter of p-aminobenzoic acid, benzocaine (25), showed activity. 1-. a local anesthetic. It is of interest to note that this drug, I 1rst introduced in 1903, is still in use today. Once the struc-iiire of cocaine was established, the presence of an alkanolamine iiiniety in cocaine prompted medicinal chemists to prepare esters "I aminobenzoic acids with acyclic alkanolamines. Formula 26 11 presents the putative relationship of the target substances with cocaine. 

Interactions in Solid-Surface Luminescence Temperature Variation. Solid-surface luminescence analysis, especially solid-surface RTF, is being used more extensively in organic trace analysis than in the past because of its simplicity, selectivity, and sensitivity (,1,2). However, the interactions needed for strong luminescence signals are not well understood. In order to understand some of the interactions in solid-surface luminescence we recently developed a method for the determination of room-temperature fluorescence and phosphorescence quantum yields for compounds adsorbed on solid surfaces (27). In addition, we have been investigating the RTF and RTF properties of the anion of p-aminobenzoic acid adsorbed on sodium acetate as a model system. Sodium acetate and the anion of p-aminobenzoic acid have essentially no luminescence impurities. Also, the overall system is somewhat easier to study than compounds adsorbed on other surfaces, such as filter paper, because sodium acetate is more simple chemically. 

Solid-surface fluorescence and phosphorescence quantum yield values were obtained from +23° to -180°C for the anion of p-aminobenzoic acid adsorbed on sodium acetate (11). Fhosphorescence lifetime values were also obtained for the adsorbed anion from +23° to -196°C. Table 1 gives the fluorescence and phosphorescence quantum yield values acquired. The fluorescence quantum yield values remained practically constant as a function of temperature. However, the phosphorescence quantum yield values changed substantially with temperature. The phosphorescence lifetime experiments indicated two decaying components. Each component showed a gradual increase in phosphorescence lifetime with cooler temperatures, but then the increase appeared to level off at the coldest temperatures. 

Several fundamental luminescence parameters were calculated for the anion of p-aminobenzoic acid on sodium acetate (11). The triplet formation efficiency (( ), the rate constant for phosphorescence... 

The phosphorescence lifetimes for the p-aminobenzoic acid anion adsorbed on sodium acetate as a function of temperature were evaluated in a manner similar to the one discussed by Oelkrug and coworkers (,28-30) for polycyclic aromatic hydrocarbons adsorbed on y-alumina. In general, the solid-surface phosphorescence lifetime cutrves for the anion of p-aminobenzoic acid followed Equation 2. 

Table I. Fluorescence and Phosphorescence Quantum Yield Values for the Anion of p-Aminobenzoic Acid Adsorbed on Sodium...

Sodium Acetate-Sodium Chloride Mixtures. Ramasamy and Hurtubise (12) obtained RTF and RTF quantum yields, triplet formation efficiency, and phosphorescence lifetime values for the anion of p-aminobenzoic acid adsorbed on sodium acetate and on several sodium acetate-sodium chloride mixtures. Rate constants were calculated for phosphorescence and for radiationless transition from the triplet state. The results showed that several factors were important for maximum RTF from the anion of p-aminobenzoic acid. One of the most important of these was how efficiently the matrix was packed with sodium acetate molecules. A similar conclusion was found for RTF however, the RTF quantum yield increased more dramatically than the RTF quantum yield. 

Figure 4. Graphs of fluorescence quantum yield and phosphorescence quantum yield ( ) versus log of the ratio of millimoles of dissolved sodium acetate to millimoles of p-aminobenzoic acid anion. (Reproduced from reference 12. Copyright 1988 American Chemical Society.)...

Two mechanisms of chromosomal resistance have been identified. A mutation of dihydropteroate synthetase (DHPS) in Strep, pneumoniae produces an altered enzyme with reduced affinity for sulphonamides. Hyperproduction of p-aminobenzoic acid (PABA) overcomes the block imposed by inhibition ofDHPS. The specific cause of PABA hyperproduction is unknown, though chromosomal mutation is the probable cause. 

Audus and Quastel (4) have found that the presence of p-aminobenzoic acid exerts an antagonism, though a relatively feeble one, to the root growth inhibitory actions of 2,4-dichlorophenoxyacetic acid, 2-chloro-4-methylphenoxyacetic acid, 2-naphthoxyacetic acid, and 2-indoleacetic acid. For any marked degree of antagonism the concentration ratio of p-aminobenzoic acid to the growth substance must be of the order of 10,000. This relatively feeble action is ii marked contrast to the effect of p-aminobenzoic acid on the... 

Table 3 Extent of Urinary Excretion of p-Aminobenzoic Acid (PABA) and Its Acetyl Metabolite as a Function of Route of Administration and Ingestion of Fat... 

Fig. 9 Phase solubility diagram showing the changes in the apparent aqueous solubility of p-aminobenzoic acid (PABA) brought about by the addition of the complexing agent, caffeine, at 30°C. (The data are adapted from Ref. 51.)...

J.C. Sutherland and Griffin incorporated tritium-labelled thymine into DNA and irradiated it with 313 nm light in buffered saline in the presence of p-aminobenzoic acid for up to 12 min. After separation of the products by TLC, the radioactivity was associated with a fraction which had the characteristic RF of dimers. When the hydrolysate from a 313 nm irradiated sample was re-irradiated at 254 nm and then chromatographed, the radioactivity had the mobility of thymine monomer. This is characteristic of pyrimidine cyclobutyl dimers which were known to be photosynthesized at 313 nm and photodegrad-ed to monomers at 254 nm. Although not degraded itself, the p-aminobenzoic acid clearly acted as a photosensitizer for the DNA-damaging thymine dimerization [40]. 

As public consciousness of the harmful effects of exposure to ultraviolet light (skin cancer, premature ageing, etc.) has increased, there has been a substantial increase in the use of sunscreens. These sunscreens have, however, been associated with a number of reported problems such as phototoxicity and photoallergy. The use of p-aminobenzoic acid (PABA) and its derivatives has been discontinued due to their ability to... 

Surface-enhanced Raman scattering using a silver-coated alumina support selectively enhanced the spectrum of p-aminobenzoic acid. This allowed the determination of this compound at low ppm levels in vitamin B complex354,355. 

Acetylated MS-222 was found in much higher concentrations in the urine than in the blood of rainbow trout. This suggests that the kidney concentrated the drug metabolite, or that MS-222 was acetylated in the kidney and excreted in the urine (28). Weber (31) stated that acetylation of p-aminobenzoic acid and sulfamethazine is catalyzed by most of the tissues in the body. He showed that in rabbits the acetylation of these amines by the kidney of rabbit is a small percentage of the total acetylation capability, but that the kidney is involved in this biotransformation. 

Mannich, C. Krosche, W. Arch. Pharm. 1912, 250, 647. Carl U. F. Mannich (1877-1947) was bom in Breslau, Germany. After receiving a Ph.D. at Basel in 1903, he served on the faculties of Gottingen, Frankfurt and Berlin. Mannich synthesized many esters of p-aminobenzoic acid as local anesthetics. 

Oxidation of 2-acetyldibenzothiophene with selenium dioxide in dioxane gave 2-dibenzothiopheneglyoxylaldehyde (129) (27%, penta-hydrate), which condensed with 2 moles of p-aminobenzoic acid to yield the corresponding aminal. Both compounds possessed antiviral activity. 

Sulfanilamide, whose structure is similar to the structure of p-aminobenzoic acid, competes with p-aminobenzoic acid for inclusion in the folic acid molecule. In short, by taking the place of p-aminobenzoic acid, it interferes with the biosynthesis of folic acid. As a result, the misled enzymes construct a false molecule of folic acid, which is not able to carry out the vital function of true folic acid. 

Thus sulfonamides are bacteriostatic drugs that inhibit bacterial growth by interfering with the microbial synthesis of folic acid. More specifically, sulfonamides block the biosynthetic pathway of folic acid synthesis, thus competitively inhibiting the transformation of p-aminobenzoic acid to folic acid (mediated by the enzyme dihydropteroate synthetase), which allows them to be considered as antimetabolites. 

Dapsone, which was first proposed in 1941, possesses both bactericidal as weU as bacteriostatic activity with respect to Mycobacterium leprae and Mycobacterium tuberculosis. It is used to treat patients with herpetiform dermatitis. It is believed that the mechanism of its action consists of competitive inhibition of the enzyme dihydroprotease synthetase, which blocks synthesis of folic acid in microorganisms, allowing it to also be viewed as an analog of p-aminobenzoic acid. Synonyms of this drug are avosulfon, croysulfon and others. 

Para-aminosalicylic Acid (PAS), like the sulfonamides (see Chapter 44), is a structural analogue of p-aminobenzoic acid (PABA). It is a folate synthesis antagonist that interferes with the incorporation of PABA into folic acid. PAS is bacteriostatic, and in vitro, most strains of M. tuberculosis are sensitive to a concentra-... 

Procaine is a derivative of p-aminobenzoic acid, and is a one of the oldest used ester-type local anaesthetic agents [1], The compound was originally developed by Einhom [2,3], and later with and Uhlfelder [4]. This anti-arrhythmic drug itself has a short half-life, but is able to form salts with other drugs which causes an increase in the duration of action [5]. 

A third method of synthesis employs alkylation of the sodium salt of p-aminobenzoic acid by 2-chlorotriethylamine. 

Prepd by interaction of p-aminobenzoic acid with nitrous acid. Used as intermediate and for prepn of synthetic drugs (Refs 3 4)... 

---