1-Naphthoic acid chloride

Nafcillin Nafcillin, [25-(2a,5a,6j3)]-3,3-dimethyl-7-oxo-6-(2-ethoxy-l-naphthamido)-4-thia-l-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.4), is synthesized by acylating 6-APA with 2-ethoxy-1-naphthoic acid chloride in the presence of triethylamine [18-20]. 

The coupling component 26 is prepared like a Naphthol AS derivative. 5-Ami-nobenzimidazolone is treated with 2-hydroxy-3-naphthoic acid chloride or with 2-hydroxy-3-naphthoic acid and phosphorus trichloride in an organic solvent (Sec. 2.1.2). 

Naphtho[Moxepine-4-one benzolog 473 was obtained in a yield of 10% from 8-phenoxy-l-naphthoic acid chloride as a result of intramolecular... 

Into a solution containing a-naphthoic acid chloride in benzene with agitation and cooling for 0.5 h a benzene solution of N,N-diethylamine-ethyl-N -(n-butyl)amine is dropped. As the dropping is ended, the solution is kept under agitation in a water bath for 3 h. 

Benzoic acid and naphthoic acid are formed by the oxidative carbonylation by use of Pd(OAc)2 in AcOH. t-Bu02H and allyl chloride are used as reoxidants. Addition of phenanthroline gives a favorable effect[360], Furan and thiophene are also carbonylated selectively at the 2-position[361,362]. fndole-3-carboxylic acid is prepared by the carboxylation of 1-acetylindole using Pd(OAc)2 and peroxodisulfate (Na2S208)[362aj. Benzoic acid derivatives are obtained by the reaction of benzene derivatives with sodium palladium mal-onate in refluxing AcOH[363]. 

A significant group of carbonamides are the Naphtol products formed by condensation of 2-hydroxy-3-naphthoic acid (via its acid chloride) with a wide range of arylamines. The simplest example, Naphtol AS from aniline, is typical, and manufacture is accompHshed by suspending the acid ia a solvent such as toluene, preforming the acid chloride by addition of phosphoms trichloride, and then adding the aniline. 

Hydroxy-3-naphthoic acid (1.BB grams) was dissolved in hot aqueous sodium hydroxide (0.5N 20 ml) and the resulting solution was slowly added to a solution of N-benzyl-N,N-dimethyl-N-2-phenoxyethylammonium chloride (2.9 grams) in water (5 ml). A gum separated at first but it solidified on scratching. After the addition was complete, the mixture was allowed to stand at room temperature for 2 hours and then filtered. The residue was washed with water and dried in vacuo to give N-benzyl-N,N-dimethyl-N-2-phenoxyethylammonium 2-hydroxy-3-naphthoate, MP 170°-171°C. 

The method described above may be used for the preparation of a wide variety of butenolides substituted in the arylidene ring with either electron-withdrawing or electron-releasing substituents. y-Lactones such as a-benzylidene-7-phenyl-A 1 -bu-tenolide are isoelectronic with azlactones, but have received much less attention. Like the azlactone ring, the butenolide ring may be opened readily by water, alcohols, or amines to form keto acids, keto esters, or keto amides.7 a,-Benzylidene-7-phenyl-A3,1 -butenolide is smoothly isomerized by aluminum chloride to 4-phenyl-2-naphthoic acid in 65-75% yield via intramolecular alkylation. 

It will be recalled that certain local anesthetic amides, such as procainamide and lidocaine, are active antiarrythmic agents. Annelation of a second aromatic ring is consistent with bioactivity. Bunaftine (21) is such an agent, prepared simply from reaction of the acid chloride of 1-naphthoic acid and... 

Fig. 17 Plot of the flux, J, of 2-naphthoic acid as a function of the square root of the rotation speed, to, in 0.01 M HC, at an ionic strength p, = 0.5 M (potassium chloride) at 25°C. The error bars represent the standard deviation for each point. (Reproduced with permission of the copyright owner, the American Pharmaceutical Association, from Ref. 114.)...

An alternative is to react 2-hydroxy-3-naphthoic acid with thionyl chloride to form the naphthoyl chloride. Condensation with the aromatic amine is then typically... 

Diazotization of the aminosulfonic acid and subsequent coupling onto the sodium salt of 2-hydroxy-3-naphthoic acid initially affords the monoazo compound in the form of its soluble sodium salt. Subsequent reaction with chlorides or sulfates of alkaline earth metals or with a manganese salt, frequently in the presence of a dispersion agent, or rosin or its derivatives, at elevated temperature yields the insoluble BONA pigment lake. 

The compounds are obtained by coupling diazotized 1-aminoanthraquinone onto 2-hydroxy-3-naphthoic acid, followed by separation, drying, and conversion into the azo dye acid chloride. Condensation with amines (structure 81) is achieved in an aprotic organic solvent. 

Bephenium Bephenium, 3-hydroxy-2-naphthoat benzyldimethyl(2-phenoxyethyl) ammonia (38.1.37), is made by reacting the sodium salt of 3-hydroxy-2-naphthoic acid with benzyldimethyl(2-phenoxyethyl)ammonia chloride (38.1.36). This is in turn made from benzyl chloride and Af-(2-phenoxyethyl)dimethylamine (38.1.35), which is synthesized by reacting sodium phenolate with 2-dimethylaminoethylchloride [41,42]. 

Diazotise 223 g. of 2-naphtliylamine-l-sulphonic acid as detailed under fi-Bromonaphthalene in Section IV,62. Prepare cuprous cyanide from 125 g. of cupric sulphate pentahydrate (Section IV,66) and dissolve it in a solution of 65 g. of potassium cyanide in 500 ml. of water contained in a 1-litre three-necked flask. Cool the potassium cuprocyanide solution in ice, stir mechanically, and add the damp cake of the diazonium compound in small portions whilst maintaining the temperature at 5-8°. Nitrogen is soon evolved and a red precipitate forms gradually. Continue the stirring for about 10 hours in the cold, heat slowly to the boiling point, add 250 g. of potassium chloride, stir, and allow to stand. Collect the orange crystals which separate by suction filtration recrystallise first from water and then from alcohol dry at 100°. The product is almost pure potassium 2-cyanonaphthalene-l-sulphonate. Transfer the product to a 2-litre round-bottomed flask, add a solution prepared from 400 ml. of concentrated sulphuric acid and 400 g. of crushed ice, and heat the mixture under reflux for 12 hours. Collect the -naphthoic acid formed (some of which sublimes from the reaction mixture) by suction filtration... 

Naphthoyl chloride is conveniently prepared from /3-naphthoic acid (Org. Syn. 17, 65) and phosphorus pentachlo-ride. A mixture of 57.4 g. (0.33 mole) of acid and 69 g. (0.33 mole) of phosphorus pentachloride in a 250-cc. modified Claisen distilling flask is warmed on a steam bath in a hood. As soon as the vigorous reaction sets in, the flask is removed from the steam bath until the rapid evolution of hydrogen chloride has moderated, then warmed on the steam bath for one-half hour. After removal of the phosphorus oxychloride at diminished pressure, using a water pump, the acid chloride is distilled. The fraction boiling at i6o-i62°/i 1 mm. (bath temperature 170-180°) weighs 57 60 g. (90-95 per cent of the theoretical amount) and melts at 51-52°. The distillation should be carefully conducted, and a quite colorless product should result. 

An attempted synthesis of 9-methylnaphtho[crf]oxepine-2-one 494 by heterocyclization of 8-acetyl-1-naphthoic acid 491 (R = Me, R = H) has failed. In acidic medium or on heating acid 491 to 150°C, as well as under formation conditions for the acid chloride or ester from acid 491, 2-acetylacenaphthene-l-one 495 is obtained (79ZOR1562). A synthesis of tribenzo[c]oxepine derivatives 499 and 501 has been described as resulting from heterocyclization of the products of reduction (498) or oxidation (500) of 4-formyl-5-carboxyphenanthrene 497. The latter compound was obtained on ozonolysis of pyrene 496 [71JCS(C)729]. 

Naphthoyl chloride. This compound may be prepared from 57.4 g (0.33 mol) of 2-naphthoic acid and 69 g (0.33 mol) of phosphorus pentachloride following the procedure described above for p-nitrobenzoyl chloride. After removing the phosphorus oxychloride by distillation, the product is collected as a fraction of b.p. 160-162 °C/11 mmHg. This solidifies on cooling to a colourless solid, m.p. 51-52°C The yield is 60 g (95%). 

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