Category: 5204-46-6

Los, Johannes published the artcileHydrolytic dissociation constants of substituted 4-aminobenzoic acids, SDS of cas: 5204-46-6, the publication is Recueil des Travaux Chimiques des Pays-Bas (1967), 86(6), 609-21, database is CAplus.

The 4 individual pK values for 4-aminobenzoic acid, the following acids of the general formula 2,6,4-X(Y)(H2N)C6H2CO2H (X and Y given): H, Me; H, Cl; H, Br; H, NO2; H, OH; H, MeO; Me, Me; Et, Et; Cl, Cl; Br, Br; and 3,4-Br(H2N)C6H3CO2H are calculated from the pKI and pKII values. The hydrolytic dissociation constants, KI and KII, are determined in aqueous solutions at 50°. The effect of the CO2H group on the NH3+ → NH2 dissociation is discussed; large ΔpK1′ values are obtained for most of the acids. The effect of the CO2- group on the NH3+ → NH2 dissociation and mesomeric stabilization by CO2H and CO2- are also discussed.

Recueil des Travaux Chimiques des Pays-Bas published new progress about 5204-46-6. 5204-46-6 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Carboxylic acid,Amine,Benzene, name is 4-Amino-2,6-dichlorobenzoic acid, and the molecular formula is C7H5Cl2NO2, SDS of cas: 5204-46-6.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Hess, U. published the artcileSynthesis of 4-aryl-1λ²,2λ⁴-dithia-3,4-diaza-buta-1,2-dienes, a new dithiadiazabutadiene system, Application of 4-Amino-2,6-dichlorobenzoic acid, the publication is Pharmazie (1994), 49(2-3), 121-5, database is CAplus and MEDLINE.

4-Aryl-1λ²,2λ⁴-dithia-3,4-diaza-buta-1,2-dienes, e.g. 2-O₂NC₆H₄NHN:S:S, as representatives of a dithiadiazabutadiene structure in which sulfur occupies a different oxidation number are synthesized by reaction of diazotated acceptor-substituted aryl- and hetarylamines with thiosulfates or disodium disulfide in strong acid solution For some examples a first pharmacol. test indicate an immune-stimulating effect. Anal. examination as well as as MNDO calculation which give some mechanistical insight, supplements the new synthesis.

Pharmazie published new progress about 5204-46-6. 5204-46-6 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Carboxylic acid,Amine,Benzene, name is 4-Amino-2,6-dichlorobenzoic acid, and the molecular formula is C7H5Cl2NO2, Application of 4-Amino-2,6-dichlorobenzoic acid.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

Childress, Scott J. published the artcileElectronegative substitutions in local anesthetics of the benzoic acid ester type, Computed Properties of 5204-46-6, the publication is Journal of the American Chemical Society (1954), 3988-91, database is CAplus.

A series of substituted BzOH esters of various alkanolamines has been prepared and tested pharmacologically. Esters of the tertiary amino alcs. were prepared either by the condensation of the corresponding dialkylaminoalkyl chloride with the Na salt of the acid (method A) or by the condensation of the acid chloride with the amino alc. in the presence of excess base (method B). The esters of secondary amines were prepared by refluxing the HCl salt of the secondary amino alc. with the acid chloride (method C). The nitro esters were reduced to the amino esters by treating the HCl salts with Fe powder in H₂O or aqueous EtOH (method D). The topical and intradermal anesthetic activities of the resulting esters were measured on guinea pig wheal and rabbit cornea, resp.; comparisons were made with cocaine or procaine, to each of which the value 1 was assigned; the acute toxicities were determined in albino mice. Me₃CNH₂ (37 g.), 22 g. ethylene oxide, and 2 cc. MeOH refrigerated 3 days and the mixture fractionated gave 6.5 g. Me₃CNH(CH₂)₂OH, b. 176-7°; picrate, m. 159-60° (from H₂O). 2,4-Cl(H₂N)C₆H₃CO₂H (34.3 g.), 30 g. BuBr, and 13.2 g. KOH in 250 cc. 75% EtOH refluxed overnight, the mixture treated with 13.2 g. KOH and 30 g. BuBr, refluxed 8 hrs., concentrated in vacuo, made basic with KOH, extracted with Et₂O, and acidified, the solid precipitate (20 g.) extracted with 3 l. boiling H₂O, the solution let stand, the procedure repeated with the mother liquor, and the resulting crystals recrystallized 3 times from 95% EtOH yielded 7.5 g. 2,4-Cl(BuNH)C₆H₃CO₂H (I), white crystals, m. 112-14°; the residue from the H₂O extraction recrystallized twice from absolute EtOH gave 2,4-Cl(Bu₂N)C₆H₃CO₂H, white crystals, m. 127-9°. 2,6,4-Cl₂(O₂N)C₆H₂Me (12 g.) in 50 cc. pyridine and 40 cc. H₂O, the mixture heated to the b.p., treated at intervals with six 4.3-g. portions KMnO₄, and filtered, the filtrate concentrated in vacuo to 1/4 its original volume and treated with concentrated HCl, the precipitate dissolved in aqueous NaOH to remove 6 g. unreacted material, the solution acidified, and the yellow crystalline precipitate (2 g.) repeatedly recrystallized from H₂O and dried gave 2,6,4-Cl₂(O₂N)C₆H₂CO₂H (II), white crystals, m. 172-4° with sintering at 157°. II (7 g.) refluxed 4 hrs. with 25 g. SOCl₂, and the resulting crude acid chloride treated with EtOH gave a poor yield of the Et ester, but yielded some anhydride of II, yellow needles, m. 190-1.5° (from EtOH). II (1.9 g.) and 1.5 g. 5% Pd-C added to 60 cc. MeOH, the mixture treated with stirring during 5 min. with 1 g. N₂H₄ in 5 cc. MeOH, let stand over the weekend, filtered, concentrated to 10 cc., poured into 25 cc. H₂O, and acidified, and the precipitate recrystallized twice from H₂O yielded 0.4 g. 2,6,4-Cl₂(H₂N)C₆H₂CO₂H (III), cream-colored crystals, m. 178-9° (decomposition). The following alkyl ester of ο-ClC₆H₄CO₂H HCl salts [alkyl group, m.p., method of preparation, local anesthetic activity compared to cocaine (topical) and procaine (intradermal), and the subcutaneous and the intravenous LD₅₀ in mg./kg. given] were prepared: Et₂N(CH₂)₂, 127-8° (from 95% EtOH), A, 0, 0.4, >1000, 120; Me₂CHCH₂NH(CH₂)₂, 141-2° (from EtOH-Et₂O), C, 0, 1.5, >1000, 75; EtMeCHNH(CH₂)₂, 181-3° (95% EtOH), C, 0, 1.2, >1000, 91; β-cyclohexylaminoethyl, 203-5° (from 50% EtOH), C, 0.3, 1,2, >1000, 98; β-cyclohexylaminoisopropyl, 174-5°, C, 1.7, 1.1, 250, 36. The following ester HCl salts of 3,4-Cl₂C₆H₄CO₂H (same data given): Et₂N(CH₂)₂, 178.5-80° (from EtOAc-EtOH), B, 0, 0.6, 840, 84; EtMeCHNH(CH₂)₂, 180-2° (from 95% EtOH), C, 0.3, 0.8, 510, 120. The following ester HCl salts of 2,4-Cl(O₂N)C₆H₃CO₂H (m.p. and method given): Et₂NCHMeCH₂, 150.5-2.5°, B; Et₂NCH₂CHMe, 145-8° (from EtOH-Et₂O), B; Et₂N(CH₂)₃, 125-6° (from EtOH-Et₂O), B; Me₂CHNH(CH₂)₂, 188-9°, C; BuNH(CH₂)₂, 162-3.5°, C; Me₂CHCH₂NH(CH₂)₂, 172-4°, C; EtMeCHNH(CH₂)₂, 160-1°, C; Me₃CNH(CH₂)₂, 190-2°, C; Et₂CHNH(CH₂)₂, 162-4°, C; BuNH(CH₂)₃, 140-1°, C; EtMeCHNH(CH₂)₃, 160-3°, C; β-cyclohexylaminoethyl, 177-8°, C; 2-cyclohexylamino-1-propyl, 179-80.5°, C; 1-cyclohexyl-2-propyl, 171-2.5°, C; β-cyclohexylaminoisopropyl, 182.5-84°, C; 2-cyclohexylamino-1-phenylethyl, 196-8°, C. 2,4-Br(O₂N)C₆H₃CO₂(CH₂)₂NHCHEtMe.HCl, 157-8°, C. 2,4-(O₂N)₂C₆H₃CO₂(CH₂)₂NEt₂, 137-9° (from EtOH-Et₂O), B (all nitro esters, except where otherwise stated, were recrystallized from EtOH). The following alkyl ester HCl salts of 2,4-Cl(H₂N)C₆H₃CO₂H (all by method D) (alkyl group, m.p., activity, and toxicity given): Et₂NCHMeCH₂, 156.5-7.5° (from EtOH-EtOAc), 1.1, 2.2, 240, 44; Et₂NCH₂CHMe, 156-7°, 1.3, 3.1, 220, 55; Et₂N(CH₂)₃, 198.5-9.5°, 2.9, 2.5, 205, 50; Me₂CHNH(CH₂)₂(HCO₂H salt), 163-5°, 0.9, 1.0, 900, 84; BuNH(CH₂)₂, 161-3°, 0.9, 6.0, 320, 47; Me₂CHCH₂NH(CH₂)₂, 215-17°, 1.3, 4.4, 260, 50; EtMeCHNH(CH₂)₂, 195.5-97°, 2.6, 4.1, 570, 45; (HCO₂H salt), 152-2.5°, 2.3, 4.9, 670, 46) [0.5(CH₂CO₂H)₂ salt], 192-4°, -, 4.9, -, -]; Me₂CHNH(CH₂)₂, 270° (decomposition), 1.0, 1.0, 750, 63; Et₂CHNH(CH₂)₂(HCO₂H salt), 145-6.5°, 1.9, 1.3, 740, 37; BuNH(CH₂)₃, 168-70°, 1.8, 3.1, 140, 23; EtMeCH(CH₂)₃, 208-9.5°, 2.7, 1.4, 220, 29; β-cyclohexylaminoethyl, 224.5-26°, 2.4, 3.1, 280, 29; 2-cyclohexylaminopropyl (HCO₂H salt), 162.5-64°, 3.0, 2.1, 330, 24; β-cyclohexylamino-2-propyl, 159-61°, 3.4, 3.1, 57, 17; 3-cyclohexylaminoisopropyl, 188.5-9.5°, 2.2, 3.4, 120, 17; 2-cyclohexylamino-1-phenylethyl, 239-41° (decomposition), -, -, -, -; 2,4-Br(H₂N)C₆H₃CO₂(CH₂)₂NHCHEtMe, 202-4°, 2.5, 2.7, 450, 43. The following ester HCl salts of 4,2-H₂N(O₂N)C₆H₃CO₂H by method A (same data given): Et₂N(CH₂)₂, 177-9°, 0.2, 1.4, 850, 130; Et₂NCHMeCH₂, 182-5°, 0, 1.5, 800, 71; Et₂N(CH₂)₃, 221-3°, 0.5, 1.0, 430, 49. The following ester salts of I (same data given) by method A: Me₂N(CH₂)₂ HCl salt monohydrate, 84-6° (from EtOH-EtOAc), 0.1, 1.9, 1000, 72; Me₂N(CH₂)₂ di-HCl salt, 167-70° (decomposition), -, -, -, -; Et₂N(CH₂)₂ di-HCl salt, 151-4°, -, -, -, – (all previous ester salts were recrystallized from EtOH, except where otherwise indicated). The Et₂N(CH₂)₂ ester HCl salts of the following acids (m.p., method, activity, and toxicity given): 2,5-Cl(O₂N)C₆H₃CO₂H, 197-8° (from EtOH), B, -, -, -, -; 2,5-Cl(H₂N)C₆H₃CO₂H, 152.5-4.5° (from iso-PrOH), D, 0, 0.6, >1200, 110; 3,4-Cl(H₂N)C₆H₃CO₂H, 148-50° (from EtOH-EtOAc), A, 1.2, 0.7, >450, 45; II, 170-1° (from EtOH), A, -, -, -, -; III, 154-5.5° (from EtOH-EtOAc), D, 2.8, 3.5, 130, 31; 3,5,4-Cl₂(H₂N)C₆H₂CO₂H, 237-8° (from EtOH), A, 0.7, 2.0, 290, 44. The EtMeCHNH(CH₂)₂ ester HCl salts of the following acids (same data given): 2,5-Cl(O₂N)C₆H₃CO₂H, 158.5-9.5° (from EtOH), C, -, -, -, -; 2,5-Cl(H₂N)C₆H₃CO₂H, 121-3° (from iso-PrOH), D, 0, 2.0, >1200, 75; 3,4-Cl(O₂N)C₆H₃CO₂H, 174-5° (from EtOH), C, -, -, -, -; 3,4-Cl(H₂N)C₆H₃CO₂H HCO₂H salt, 108-9° (from EtOH-EtOAc), D, 0.8, 1.5, 490, 45; 4,3-Cl(O₂N)C₆H₃CO₂H, 185-7° (from EtOH), C, -, -, -, -; 4,3-Cl(H₂N)C₆H₃CO₂H, 179-80.5°, D, 0.3, 2.0, 570, 68. The amino alc. in the preparation of IV neutralized incompletely gave N-[2-(2-chloro-4-nitrobenzoxy)-1-propyl]-N-cyclohexyl-2-chloro-4-nitrobenzamide) cream-colored solid, m. 156.5-58° (from CHCl₃-Et₂O) as a by-product. 2,4-(O₂N)₂C₆H₃CO₂(CH₂)₂NEt₂ (0.6 g.) in 20 cc. EtOH and 1 cc. 3N NH₄OH treated at room temperature 0.5 hr. with H₂S, the mixture filtered, and the filtrate concentrated gave 0.2 g. 4,2-HONH(O₂N)C₆H₃CO₂(CH₂)₂NEt₂, m. 170-2° (from EtOH) having topical activity 0, intradermal activity 0.5, subcutaneous LD₅₀ 790, and intravenous LD₅₀ 55.

Journal of the American Chemical Society published new progress about 5204-46-6. 5204-46-6 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Carboxylic acid,Amine,Benzene, name is 4-Amino-2,6-dichlorobenzoic acid, and the molecular formula is C7H5Cl2NO2, Computed Properties of 5204-46-6.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics

McManus, E. C. published the artcileUse of coccidia to study the structure-activity relations of a series of p-aminobenzoic acid antagonists, Computed Properties of 5204-46-6, the publication is Develop. Ind. Microbiol. (1965), 44-7, database is CAplus.

Young coccidiosis-susceptible chicks were fed a standard laboratory ration with graded concentrations of test chemicals added just prior to use. On the 2nd day of the test, the chicks were inoculated orally with 100,000 sporulated oocysts of Eimeria maxima; 6 days later birds were killed and weighed, the small intestine homogenized with water, and the oocysts counted. The min. effective diet concentrations of 28 derivatives of p-aminobenzoic acid (I) were determined together with the percent reduction of oocyst count. Remarkably potent anticoccidial compounds were found in a series of ortho-substituted derivatives of I. Groups with high coccidiostatic activity conferring effects were lower alkoxy, alkylthio, and alkyl amino with approx. similar size and shape. The most active compounds, capable of reducing the oocyst count below 25% were the ο-ethoxy derivative, its esters, and N-acyl derivatives, and the ο-chloro, ο-methoxy, ο-isopropoxy, ο-ethyl, and ο-thioethyl derivatives of I. Me 4-acetamido-2-ethoxybenzoate (ethopabate) (II) reduced the oocyst count to nil. The methyl, chloro, nitro, and methoxy derivatives conferred anticoccidial activity when substituted in the ortho position, but not in meta position. Disubstituted derivatives were inactive. The in vivo anticoccidial activity of II and sulfaquinoxaline (III) was overcome completely by simultaneous administration of I. Both II and III potentiated the anticoccidial activity of pyrimethamine. Cross resistance occurred between II and III for many strains of coccidia. The dose-response curves of II and III were parallel, and their anticoccidial activities were additive. II was about 150-fold more potent than III for control of certain strains of E. maxima and Ε. brunetti, and less potent for Ε. tenella. Both II and III were assumed to inhibit biosynthesis of folic acid-type compounds at different steps in the sequence of reactions for synthesis of tetrahydrofolic acid.

Develop. Ind. Microbiol. published new progress about 5204-46-6. 5204-46-6 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Carboxylic acid,Amine,Benzene, name is 4-Amino-2,6-dichlorobenzoic acid, and the molecular formula is C7H5Cl2NO2, Computed Properties of 5204-46-6.

Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics