50-86-2

Basic information

• Product Name: 4-Acetamidosalicylic acid
• Synonyms: 2-HYDROXY-4-ACETYLAMINOBENZOIC ACID;4 ACETAMIDO SALICYLIC ACID;4-ACETAMIDO-2-HYDROXYBENZOIC ACID;4-(acetylamino)-2-hydroxy-benzoicaci;4-(acetylamino)-2-hydroxybenzoicacid;4-acetamido-2-hydroxy-benzoicaci;4-acetamido-salicylicaci;4-acetaminosalicylicacid
• CAS NO: 50-86-2
• Molecular Formula: C₉H₉NO₄
• Molecular Weight: 195.17
• EINECS: 200-069-9
• Product Categories: Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Aromatics
• Mol File: 50-86-2.mol
• Article Data: 18

Chemical Properties

• Melting Point: 227-229°C
• Boiling Point: 470.6 °C at 760 mmHg
• Flash Point: 238.4 °C
• Appearance: off-white solid
• Density: 1.462 g/cm³
• Vapor Pressure: 1.16E-09mmHg at 25°C
• Refractive Index: 1.661
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 4-Acetamidosalicylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Acetamidosalicylic acid(50-86-2)
• EPA Substance Registry System: 4-Acetamidosalicylic acid(50-86-2)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 50-86-2(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

N-Acetyl-4-aminosalicylic Acid (Metoclopramide EP Impurity H) is hydroxybenzoic acid that is a versatile reactant used in the preparation of salicylanilide derivatives as inhibitors of the protein tyrosine kinase epidermal growth factor receptor.

Definition

ChEBI: A amidobenzoic acid that consists of salicylic acid bearing an acetamido substituent at position 4.

InChI:InChI=1/C9H9NO4/c1-5(11)10-6-2-3-7(9(13)14)8(12)4-6/h2-4,12H,1H3,(H,10,11)(H,13,14)

Synthetic route

acetic anhydride (108-24-7) + 4-Aminosalicylic acid (65-49-6) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
In acetone for 24h; Cooling with ice;	95%
With sodium hydroxide In water at 60℃; for 4h; pH=6-7;	91%
In acetone for 6h;	91%

4-Aminosalicylic acid (65-49-6) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
With acetic anhydride In ethanol	92%
With acetic anhydride In ethanol	72.3 g (74.15%)

4-Aminosalicylic acid (65-49-6) + acetyl chloride (75-36-5) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
In pyridine for 2h; Inert atmosphere; Reflux;	85%
With pyridine at 0℃; for 2h; Inert atmosphere; Reflux;	85%
With pyridine

acetic anhydride (108-24-7) + 4-Aminosalicylic acid (65-49-6) + acetic acid (64-19-7) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
for 0.25h; Reflux;	85%

acetic anhydride (108-24-7) + sodium p-aminosalicylate (133-10-8) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
In water at 45℃; for 4h;	84.12%

sodium p-aminosalicylate (133-10-8) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
With hydrogenchloride; acetic anhydride In water	56%

p-(acetylamino)benzoic acid (556-08-1) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
With oxygen; potassium acetate; palladium diacetate; p-benzoquinone In N,N-dimethyl acetamide at 115℃; under 760.051 Torr; for 15h;	52%

1-amino-3-acetylamino-6-carboxy-benzene (43134-76-5) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
With sodium hydrogen sulfate; sodium nitrite

2-hydroxy-4-nitrobenzoic acid (619-19-2) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: nickel-aluminium-alloy; aq. NaOH solution 2: pyridine View Scheme

4-Aminosalicylic acid (65-49-6) + acetylcoenzyme A (72-89-9) → 4-acetamidosalicylic acid (50-86-2)

Conditions	Yield
With Mycobacterium tuberculosis H37Rv arylamine N-acetyltransferase In aq. buffer at 37℃; pH=7.5; Enzymatic reaction;

sebacoyl chloride (111-19-3) + 4-acetamidosalicylic acid (50-86-2) → 1,10-bis-4-acetamidosalicyl-sebacate (537048-78-5)

Conditions	Yield
Stage #1: sebacoyl chloride; 4-acetamidosalicylic acid With pyridine In N,N-dimethyl-formamide at 0 - 20℃; for 6.08333h; Stage #2: With hydrogenchloride In water; N,N-dimethyl-formamide pH=2;	98%

ethyl bromide (74-96-4) + 4-acetamidosalicylic acid (50-86-2) → 4-acetylamino-2-ethoxy-benzoic acid ethyl ester (2486-67-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4h;	90.41%

4-acetamidosalicylic acid (50-86-2) + potassium carbonate (584-08-7) + dimethyl sulfate (77-78-1) → methyl 4-(acetylamino)-o-anisate (4093-29-2)

Conditions	Yield
In acetone	89%

1-bromo-hexane (111-25-1) + 4-acetamidosalicylic acid (50-86-2) → 4-acetamido-2-hexyloxy-benzoic acid hexyl ester (1198104-04-9)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate; potassium iodide In acetone for 50h; Reflux; Inert atmosphere;	82%

C13H13BrO + 4-acetamidosalicylic acid (50-86-2) → C22H22BrNO5

Conditions	Yield
With morpholine In diethyl ether at 25℃; Green chemistry;	75%

4-acetamidosalicylic acid (50-86-2) → 4-acetamido-2-hydroxy-5-nitrobenzoic acid (82378-91-4)

Conditions	Yield
With sodium nitrate; trifluoroacetic acid at 0℃; for 3h;	70%
Stage #1: 4-acetamidosalicylic acid With nitric acid; trifluoroacetic acid at 20 - 50℃; for 3h; Stage #2: In acetone for 0.25h; Reflux;	28%
With nitric acid; acetic anhydride at -20 - -15℃; for 24h;	23%
With sulfuric acid; nitric acid
With trifluoroacetic acid; sodium nitrite at -5 - 0℃; for 2h;

4-acetamidosalicylic acid (50-86-2) + methyl halide → 4-acetylamino-2-methoxy-benzoic acid (55304-05-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h;	63%

3,5-dimethylphenyl iodide (22445-41-6) + 4-acetamidosalicylic acid (50-86-2) → N-(5-hydroxy-3',5'-dimethyl-[1,1'-biphenyl]-3-yl)acetamide

Conditions	Yield
With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl) palladium(II) dichloride; potassium carbonate; silver carbonate In acetic acid at 150℃; for 16h;	41%
With [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(ll) dichloride; acetic acid; silver carbonate at 150℃; for 16h; regioselective reaction;	41%

boric acid (11113-50-1) + 4-acetamidosalicylic acid (50-86-2) + silver nitrate → Ag(1+)*C18H14BN2O8(1-)

Conditions	Yield
In water; acetone at 25 - 35℃; for 2h;	32%

diazomethane (186581-53-3, 908094-01-9) + 4-acetamidosalicylic acid (50-86-2) → methyl 4-acetamido-2-hydroxybenzoate (4093-28-1)

Conditions	Yield
With diethyl ether

acetic anhydride (108-24-7) + 4-acetamidosalicylic acid (50-86-2) → 4-acetamido-2-acetoxybenzoic acid (51-00-3)

Conditions	Yield
With sulfuric acid

4-acetamidosalicylic acid (50-86-2) + p-toluidine (106-49-0) → acetic acid-[3-hydroxy-4-(p-tolylimino-methyl)-anilide] (81766-23-6)

Conditions	Yield
With sodium amalgam; boric acid; sodium carbonate weitere Reagenzien: NaCl, wss. Aethanol;

4-acetamidosalicylic acid (50-86-2) + aniline (62-53-3) → acetic acid-[3-hydroxy-4-(phenylimino-methyl)-anilide] (29085-70-9)

Conditions	Yield
With sodium hydroxide; boric acid; sodium chloride anschliessend Behandeln mit Natrium-Amalgam;

4-acetamidosalicylic acid (50-86-2) → 4-acetylamino-3,5-dichloro-2-hydroxy-benzoic acid

Conditions	Yield
With tetrachloromethane; chlorine

chloroformic acid ethyl ester (541-41-3) + 4-acetamidosalicylic acid (50-86-2) + 1,1-dimethylhydrazine (57-14-7) → 7-acetylamino-3-dimethylamino-benzo[e][1,3]oxazine-2,4-dione (14780-53-1)

Conditions	Yield
With triethylamine

chloroformic acid ethyl ester (541-41-3) + 4-acetamidosalicylic acid (50-86-2) + methylamine (74-89-5) → 7-acetylamino-3-methyl-benzo[e][1,3]oxazine-2,4-dione (14780-52-0)

Conditions	Yield
With triethylamine

4-acetamidosalicylic acid (50-86-2) + dimethyl sulfate (77-78-1) → methyl 4-(acetylamino)-o-anisate (4093-29-2)

Conditions	Yield
With potassium carbonate In acetone for 26h; Heating;

4-acetamidosalicylic acid (50-86-2) + acetyl chloride (75-36-5) → 4-acetamido-2-acetoxybenzoic acid (51-00-3)

Conditions	Yield
With pyridine at 0 - 25℃; for 0.5h; Acetylation;

4-acetamidosalicylic acid (50-86-2) → 4-acetamidosalicyloyl chloride (693257-41-9)

Conditions	Yield
With thionyl chloride at 20 - 50℃; for 5.5h;

4-acetamidosalicylic acid (50-86-2) → 4-amino-2-hydroxy-N-(3-hydroxy-phenyl)-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / 5.5 h / 20 - 50 °C 2: 5.88 g / pyridine / toluene 3: 16 percent / hydrochloric acid; acetic acid / 16 h / Heating View Scheme

4-acetamidosalicylic acid (50-86-2) → 4-acetylamino-N-(3-chloro-phenyl)-2-hydroxy-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / 5.5 h / 20 - 50 °C 2: 1.47 g / pyridine / toluene / 3.5 h / 20 °C View Scheme

Upstream product

• 43134-76-5 1-amino-3-acetylamino-6-carboxy-benzene 
• 108-24-7 acetic anhydride 
• 65-49-6 4-Aminosalicylic acid 
• 75-36-5 acetyl chloride 
• 72-89-9 acetylcoenzyme A 
• 64-19-7 acetic acid 
• 133-10-8 sodium p-aminosalicylate 
• 556-08-1 p-(acetylamino)benzoic acid 
• 619-19-2 2-hydroxy-4-nitrobenzoic acid 

Downstream Products

• 51-00-3 4-acetamido-2-acetoxybenzoic acid 
• 4093-29-2 methyl 4-(acetylamino)-o-anisate 
• 112885-34-4 4-acetylamino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide 
• 112885-42-4 mosapride citrate 
• 2486-67-1 4-acetylamino-2-ethoxy-benzoic acid ethyl ester 
• 55304-05-7 4-acetylamino-2-methoxy-benzoic acid 
• 1609025-09-3 2,3-bis(4-fluorophenyl)-7-hydroxyquinoxaline-6-carboxylic acid 
• 1198104-04-9 4-acetamido-2-hexyloxy-benzoic acid hexyl ester 

Relevant articles and documents

Mycobacterium tuberculosis arylamine N-acetyltransferase acetylates and thus inactivates para-aminosalicylic acid

Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) is able to acetylate para-aminosalicylic acid (PAS) both in vitro and in vivo as determined by high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (ESI-MS) techniques. The antituberculosis activity of the acetylated PAS is significantly reduced. As a result, overexpression of TBNAT in M. tuberculosis results in PAS resistance, as determined by MIC tests and drug exposure experiments. Taken together, our results suggest that TBNAT from M. tuberculosis is able to inactivate PAS by acetylating the compound.

Aminobenzoic acid derivative and preparation method and application thereof

The invention relates to an aminobenzoic acid derivative and a preparation method and application thereof, and belongs to the field of medicinal chemistry, and the structural formula of the aminobenzoic acid derivative is shown in the specification, R is alkyl, substituted phenyl, heteroaromatic ring group or substituted styryl; R is alkyl; R is alkyl, substituted phenyl or benzyl; R is alkyl; R is guanidyl; and R is alkyl. The preparation method is simple and high in yield. Most compounds of the invention have good influenza virus neuraminidase inhibition activity.

Citric acid mosapride intermediate product and application

The invention belongs to the field of medical chemistry synthesis, and provides a preparation method of citric acid mosapride intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanaminesalt and citric acid mosapride. The 2-(4-fluorobenzoamido)ethanol and 1H-Isoindole-1,3(2H)-dione,2-(2-oxiranylmethyl) are taken as raw materials, and the intermediate product IV 4-[(4-fluorophenyl)methyl]-2-morpholinemethanamine salt is obtained after acid treating is conducted; the intermediate product IV and an intermediate V 2-oxethyl-4-acetamido-5-Chlorobenzoic acid ethyl ester compounds aretaken as raw materials, dichloromethane is taken as a solvent, and EDCI and DMAP are taken as catalysts to prepare mosapride salt; the mosapride salt is reacted with citric acid aqueous solution to prepare citric acid mosapride. The intermediate product has the advantages that products are high in yield, raw materials are easy to obtain, the production cost is low, and the intermediate product issuitable for industrialized production.