Ethyl 4-aminobenzoate, benzocaine

Medicinals. Many esters are used as pharmaceuticals (105,106). Of these, benzocaine, ethyl 4-aminobenzoate [94-09-7] is a topical anesthetic. Phenyl saHcylate [118-55-8] (1) has antipyretic, antirheumatic, and antiparasitic properties. 

SYNS AMERICAINE p-AMINOBENZOIC ACID ETHYL ESTER 4-AMINOBENZOIC ACID ETHYL ESTER ANESTHESIN ANESTHONE BENZOCAINE ETHYL AMINOBENZOATE ETHYL-p-AMNOBENZOATE KELOFORM NORCAIN ORTHESIN PARATHESIN TOPCAINE... 

Methemoglobinemia has been reported following the topical application of benzocaine (ethyl aminobenzo-ate) to both skin and mucous membranes, with most cases occurring in infants (Haggerty 1962 Olson and McEvoy 1981). However, toxicity is uncommon (American Medical Association 1977). 

Benzocaine (ethyl / -aminobenzoate), which has a very simple structure, is used as a mild topical anesthetic in ointments for burns, insect bites, and open wounds. Note that procaine and benzocaine are different esters of the same acid, p-aminobenzoic acid. 

Ethyl aminobenzoate. See Benzocaine AT-Ethylaniline, steam distillation, 8 777 Ethylate, 10 528... 

Prilocaine Propitocaine HCl Xylonest -(2-Me-thylphenyl)-2-(propylamino)-propanamide hydrochloride 2-(Propylamino)-o-propionotoluidide hydrochloride -(a-Propylaminopropionyl)-o-to-luidine hydrochloride a-Propylamino-2 -methyl-propionanilide hydrochloride Benzocaine Anesthesin Parathesin Auralgan Otic Ethyl aminobenzoate Chemicae Eormuea Amides... 

Anesthetics. Ethyl aminobenzoate [94-09-7] (benzocaine), C9H11N02, is the only anesthetic candidate that might allow spawned-out broodstock carcasses to be used for pet or human food. Studies are still required to determine which residues remain in the carcasses (9). Electronarcosis is an alternative to chemical anesthesia that uses varying electrical frequencies to rapidly anesthetize fishes and allow gende recovery. Electronarcosis has been used effectively on tilapia (Oreochromis sp.) and the common carp (Cyprinus carpio) and the technique is being tested with other fishes (23,24). 

Benzocaine (ethyl p-aminobenzoate) is used topically by itself or in combination with menthol or phenol in nonprescription dosage forms such as gels, creams, ointments, lotions, aerosols, and lozenges to relieve pain or irritation caused by such conditions as sunburn, insect bites, toothache, teething, cold sores or canker sores in or around the mouth, and fever blisters. Benzocaine is a lipophilic local anesthetic agent with a short duration of action. 

Quite early in the quest for a simplified cocaine, the simplest structure of all was discovered in benzocaine (ethyl j -aminobenzoate) 7.14). Too insoluble to be injected, it has found a permanent place in anaesthetic therapy as a constituent of dusting powders for inflamed areas. Although so insoluble in water, it is soluble in oils, and this has opened up a second area of application. The fact that it is incapable of ionization at physiological pH values, ensures that its anaesthetic action is weak (see Section 10.5). 

Devise a synthesis of benzocaine, ethyl p-aminobenzoate (H2NC6H4CO2CH2CH3), from benzene, organic alcohols, and any needed organic or inorganic reagents. Benzocaine is the active ingredient in the topical anesthetic Orajel (Section 18.14C). 

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. 

A. Ethyl 4-Amino-3-(methylthiomethyl)benzoate [Benzoic acid, 4-amino-3-[(methylthio)methyl]-]. A 1-1., three-necked, round-bottomed flask is fitted with a mechanical stirrer, a condenser topped with a gas-inlet tube, and a two-neckcd adapter holding a low-temperature thermometer and a 100-ml., pressure-equalizing dropping funnel. The flask is charged with 10.50 g. (0.10 mole) of ethyl p-aminobenzoate [Benzocaine Benzoic acid, 4-amino-, ethyl ester] (Note 1), 300 ml. of acetonitrile, and 100 ml. of dichloromethane, is flushed with nitrogen, and is then immersed in a 40% aqueous methanol-dry ice bath maintained between... 

Benzocaine Benzocaine is the ethyl ester of 4-aminobenzoic acid (2.3.1). The classic, optimal way of benzocaine synthesis is the reduction of the nitro group of the ethyl ester of 4-nitrobenzoic acid to benzocaine by hydrogen, which generates directly in the reaction medium by the reaction of iron filings with dilute acids [24-26]. 

A somewhat different mechanism was deduced by Baker and Bailey 4f) from their own studies of the systems phenyl isocyanate and ethyl p-aminobenzoate (benzocaine) cyclohexyl isocyanate and aniline phenyl isocyanate and aniline p-methoxyphenyl isocyanate and aniline. While Craven postulates one complex. Baker and Bailey assume two complexes of the isocyanate one with the amine, and one with the product urea. 

---