487-54-7

Basic information

• Product Name: 2-HYDROXYHIPPURIC ACID
• Synonyms: TIMTEC-BB SBB000337;SALICYLURIC ACID;SALICYLGLYCINE;SALICYLGYCINE;O-HYDROXYHIPPURIC ACID;Glycine, N-(2-hydroxybenzoyl)-;Hippuric acid, o-hydroxy-;n-(2-hydroxybenzoyl)-glycin
• CAS NO: 487-54-7
• Molecular Formula: C₉H₉NO₄
• Molecular Weight: 195.17
• EINECS: 207-661-6
• Product Categories: Aromatics Compounds;Aromatics;Metabolites & Impurities
• Mol File: 487-54-7.mol
• Article Data: 7

Chemical Properties

• Melting Point: 164-169 °C
• Boiling Point: 331.83°C (rough estimate)
• Flash Point: 250.016 °C
• Appearance: White to light yellow/Powder, Crystals or Chunks
• Density: 1.3544 (rough estimate)
• Vapor Pressure: 2.08E-10mmHg at 25°C
• Refractive Index: 1.5700 (estimate)
• Storage Temp.: Store at 0°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.68±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 2-HYDROXYHIPPURIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 2-HYDROXYHIPPURIC ACID(487-54-7)
• EPA Substance Registry System: 2-HYDROXYHIPPURIC ACID(487-54-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 24/25-36/37/39-27-26
• RTECS: MR8160000
• Hazardous Substances Data: 487-54-7(Hazardous Substances Data)

Usage

Description

Salicyluric acid is an N-acylglycine in which the acyl group is specified as 2-hydroxybenzoyl. It has a role as a uremic toxin and a human xenobiotic metabolite. It is a N-acylglycine and a secondary carboxamide. It is functionally related to a glycine. It is a conjugate acid of a salicylurate.

Uses

Metabolite of Salicylic Acid (S088125). 2-Hydroxyhippuric acid is a phenol marker. Can be associated with dietary intake or bacterial overgrowth. Indicators of Detoxification: A conjugate of the amino acid glycine and hydroxybenzoic acid (salicylic acid). Intake of aspirin (salicylates) or the growth of salicylate-producing gastrointestinal bacteria may elevate levels. Also increased after the ingestion of the artificial sweetener aspartame (Nutrasweet).

Definition

ChEBI: An N-acylglycine in which the acyl group is specified as 2-hydroxybenzoyl.

Synthesis

The synthesis of Salicyluric acid is as follows:To a solution of 5 g of glycine in 50ml of 10%NaOH was stirred at room temperature upon slowaddition of salicyloyl chloride, and the resultingmixture was stirred overnight. Progress of the reaction was followed by TLC (hexane : ethylacetate, 7 : 3).Then the reaction mixture was treated with crushed iceupon stirring. Concentrated HCl was added dropwiseand stirring was continued until the mixture turnedacidic. For removing the residual benzoic acid the mixture was treated with 10-12 mL of CCl4, boiled and then filtered. A pinkish white solid was obtained, yield 90%, mp 165°C.

InChI:InChI=1/C9H9NO4/c11-7-4-2-1-3-6(7)9(14)10-5-8(12)13/h1-4,11H,5H2,(H,10,14)(H,12,13)/p-1

Synthetic route

(2-Hydroxy-benzoylamino)-acetic acid benzyl ester (178633-73-3) → Salicyluric acid (487-54-7)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol 0 deg C, then 0oom temp., overnight;	92%

glycine (56-40-6) + salicyloyl chloride (1441-87-8) → Salicyluric acid (487-54-7)

Conditions	Yield
With sodium hydroxide at 20℃;	90%
With sodium hydroxide; water Erwaermen des nach dem Ansaeuern erhaltenen Reaktionsprodukts mit wss. Natronlauge;

(2-methoxyphenyl)(methoxycarbonylmethylamino)-methanone (27796-49-2) → Salicyluric acid (487-54-7)

Conditions	Yield
	40%

ethanol (64-17-5) + 2-glycyloxy-benzoic acid ; perchlorate → Salicyluric acid (487-54-7)

Conditions	Yield
at 20℃; Kinetics;

N-salicyloyl-glycine amide (56145-98-3) → Salicyluric acid (487-54-7)

Conditions	Yield
With sodium hydroxide

2-azidoacetoxy-benzoic acid (856119-90-9) → Salicyluric acid (487-54-7)

Conditions	Yield
With acetic acid methyl ester; platinum Hydrogenation;
With palladium on activated charcoal; acetic acid Hydrogenation;

2-(N-benzyloxycarbonyl-glycyloxy)-benzoic acid → Salicyluric acid (487-54-7)

Conditions	Yield
With palladium on activated charcoal; 2-methoxy-ethanol Hydrogenolyse;

2-(N-benzyloxycarbonyl-glycyloxy)-benzoic acid benzyl ester (116601-30-0) → Salicyluric acid (487-54-7)

Conditions	Yield
With palladium on activated charcoal; 2-methoxy-ethanol Hydrogenolyse;

2-methoxycarbonyloxy-benzoyl chloride (92505-60-7) + glycine (56-40-6) → Salicyluric acid (487-54-7)

Conditions	Yield
With sodium hydroxide Behandeln des Reaktionsgemischs mit konz. Natronlauge;

2-hydroxybenzoyl azide (54539-61-6) + glycine (56-40-6) → Salicyluric acid (487-54-7)

Conditions	Yield
With sodium hydroxide

C12H17NO4Si → Salicyluric acid (487-54-7)

Conditions	Yield
With sodium hydroxide for 2h;

anionic phenyl salicylate (61141-14-8) + glycine (56-40-6) → Salicyluric acid (487-54-7) + salicylic acid (69-72-7) + phenol (108-95-2)

Conditions	Yield
With sodium hydroxide In water; acetonitrile at 35℃; Rate constant; different contents of CH3CN;

(2,4-dioxo-4H-benzo[e][1,3]oxazin-3-yl)-acetic acid (50331-25-4) + ammonium hydroxide → Salicyluric acid (487-54-7)

Conditions	Yield
at 100℃; im Rohr;

2-glycyloxy-benzoic acid amide perchlorate → Salicyluric acid (487-54-7)

Conditions	Yield
With sodium hydroxide

2-glycyloxy-benzoic acid-perchlorate → Salicyluric acid (487-54-7)

Conditions	Yield
With water

carbonylsalicylic acid → Salicyluric acid (487-54-7)

Conditions	Yield
With ammonium hydroxide at 100℃; im Bombenrohr;

2-methoxycarbonyloxy-benzoyl chloride (92505-60-7) + glycocoll ester → Salicyluric acid (487-54-7)

Conditions	Yield
With diethyl ether Verseifen des Reaktionsproduktes mit Natronlauge;

methyl salicylate (119-36-8) + sodium-salt of glycine → Salicyluric acid (487-54-7)

Conditions	Yield
With ethanol

2-hydroxybenzoyl azide (54539-61-6) + furan-2,3,5(4H)-trione pyridine (1:1) + glycine (56-40-6) → Salicyluric acid (487-54-7) + compound (mp: 230-231 degree )

perchloric acid (7601-90-3) + 2-glycyloxy-benzoic acid ; perchlorate → Salicyluric acid (487-54-7)

Conditions	Yield
at 20℃; Kinetics;

water (7732-18-5) + 2-glycyloxy-benzoic acid ; perchlorate → Salicyluric acid (487-54-7)

Conditions	Yield
at 20℃; Kinetics;

2-methoxy-ethanol (109-86-4) + 2-(N-benzyloxycarbonyl-glycyloxy)-benzoic acid benzyl ester (116601-30-0) + palladium/charcoal → Salicyluric acid (487-54-7)

Conditions	Yield
Hydrogenolyse;

2-azidoacetoxy-benzoic acid (856119-90-9) + acetic acid (64-19-7) + palladium/charcoal → Salicyluric acid (487-54-7)

Conditions	Yield
Hydrogenation;

acetic acid methyl ester (79-20-9) + 2-azidoacetoxy-benzoic acid (856119-90-9) + platinum → Salicyluric acid (487-54-7)

Conditions	Yield
Hydrogenation;

salicylic acid (69-72-7) + diazotized 4.4'-diamino-stilbene-disulfonic acid-(2.2') → Salicyluric acid (487-54-7) + compound (mp: 230-231 degree )

Conditions	Yield
Multi-step reaction with 2 steps 1: 72 percent / 1.) N-cyclohexyl-N'-<2-(4-methylmorpholin-4-ylium)ethyl>carboximide toluene-4-sulfonate; 2.) Et3N / acetonitrile / 1.) 30 min.; 2.) 0 deg C --> room temp., overnight 2: 92 percent / H2 / Pd/C / methanol / 0 deg C, then 0oom temp., overnight View Scheme

2-Methoxybenzoic acid (579-75-9) → Salicyluric acid (487-54-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 31 percent / chloroethylcarbonate / tetrahydrofuran 2: 40 percent View Scheme

2-methoxycarbonyloxy-benzoic acid (14216-34-3) → Salicyluric acid (487-54-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: PCl5 2: diethyl ether / Verseifen des Reaktionsproduktes mit Natronlauge View Scheme
Multi-step reaction with 2 steps 1: PCl5 2: NaOH-solution / Behandeln des Reaktionsgemischs mit konz. Natronlauge View Scheme

benzyl salicylate (118-58-1) → Salicyluric acid (487-54-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine 2: palladium/charcoal; 2-methoxy-ethanol / Hydrogenolyse View Scheme

salicylic acid (69-72-7) → Salicyluric acid (487-54-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: dimethylaniline; benzene 2: PCl5 3: diethyl ether / Verseifen des Reaktionsproduktes mit Natronlauge View Scheme
Multi-step reaction with 2 steps 1: PCl5; diethyl ether; pyridine 2: palladium/charcoal; 2-methoxy-ethanol / Hydrogenolyse View Scheme
Multi-step reaction with 3 steps 1: dimethylaniline; benzene 2: PCl5 3: NaOH-solution / Behandeln des Reaktionsgemischs mit konz. Natronlauge View Scheme
Multi-step reaction with 2 steps 1: chloroform; pyridine 2: platinum; methyl acetate / Hydrogenation View Scheme

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + 3-nitro-benzaldehyde (99-61-6) → 2-{4-[3-(nitrobenzylidene)-5-oxo-4,5-dihydrooxazol-2-yl]}phenyl acetate (16352-91-3)

Conditions	Yield
With sodium acetate Erlenmeyer-Plochl-Bergmann; Reflux;	88%

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + 4-hydroxy-benzaldehyde (123-08-0) → 2-{4-[4-(acetoxybenzylidene)-5-oxo-4,5-dihydrooxazol-2-yl]}phenyl acetate

Conditions	Yield
With sodium acetate Erlenmeyer-Plochl-Bergmann; Reflux;	88%

Salicyluric acid (487-54-7) + 2,2-dimethyl-3-(N-methyl-N-phenylamino)-2H-azirine (75755-40-7) → 2-Hydroxy-N-{[1-methyl-1-(methyl-phenyl-carbamoyl)-ethylcarbamoyl]-methyl}-benzamide (192046-51-8)

Conditions	Yield
In acetonitrile 0 deg C --> room temp., overnight;	86%

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + 4-dimethylamino-benzaldehyde (100-10-7) → 2-{4-[4-(dimethylamino)benzylidene]-5-oxo-4,5-dihydrooxazol-2-yl}phenyl acetate (16352-93-5)

Conditions	Yield
With sodium acetate Erlenmeyer-Plochl-Bergmann; Reflux;	85%

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + 4-chlorobenzaldehyde (104-88-1) → 2-{4-[4-(chlorobenzylidene)-5-oxo-4,5-dihydrooxazol-2-yl]}phenyl acetate

Conditions	Yield
With sodium acetate Erlenmeyer-Plochl-Bergmann; Reflux;	85%

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + 4-bromo-benzaldehyde (1122-91-4) → 2-{4-[4-(bromobenzylidene)-5-oxo-4,5-dihydrooxazol-2-yl]}phenyl acetate

Conditions	Yield
With sodium acetate Erlenmeyer-Plochl-Bergmann; Reflux;	85%

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + 3,4-dimethoxy-benzaldehyde (120-14-9) → 2-[4-(3,4-dimethoxybenzylidene)-5-oxo-4,5-dihydrooxazol-2-yl]phenyl acetate (16352-92-4)

Conditions	Yield
With sodium acetate Erlenmeyer-Plochl-Bergmann; Reflux;	80%

Salicyluric acid (487-54-7) + 3-aminodihydrothiophen-2(3H)-one hydrochloride (6038-19-3) → 2-hydroxy-N-(2-oxo-2-(2-oxotetrahydrothiophen-3-ylamino)ethyl)benzamide (1258323-53-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 60℃; for 1h;	80%

carbon suboxide (504-64-3) + Salicyluric acid (487-54-7) → [(2-Hydroxy-4,5-dioxo-4H,5H-pyrano[3,2-c]chromene-3-carbonyl)-amino]-acetic acid

Conditions	Yield
In acetone 0 deg C, 5 h then r.t., 48 h;	70%

copper(II) perchlorate hexahydrate + Salicyluric acid (487-54-7) → Cu(2+)*2C6H4(OH)CONHCH2COO(1-)*3H2O=Cu(C6H4(OH)CONHCH2COO)2*3H2O

Conditions	Yield
With triethylamine In methanol addn. of Et3N (1 equiv.) to ligand, addn. of Cu(ClO4)2 (0.5 equiv.), standing for 2-3 days (pptn.); collection (filtration), recrystn. (50% Me2CO);	70%

carbon suboxide (504-64-3) + Salicyluric acid (487-54-7) → [(2,4-Dioxo-chroman-3-carbonyl)-amino]-acetic acid

Conditions	Yield
In acetone C3O2:acetone=1:500; 0 deg C, 4 h then r.t., 48 h;	68%

Salicyluric acid (487-54-7) + cystamine dihydrochioride (56-17-7) → N,N'-(2,2'-(2,2'-disulfanediylbis(ethane-2,1-diyl)bis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(2-hydroxybenzamide) (1429128-83-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran at 60℃; for 1h;	65%

Salicyluric acid (487-54-7) + zinc(II) chloride (7646-85-7) → Zn(2+)*2C6H4(OH)CONHCH2COO(1-)*5H2O=Zn(C6H4(OH)CONHCH2COO)2*5H2O

Conditions	Yield
With triethylamine In methanol addn. of Et3N (1 equiv.) to ligand, addn. to ZnCl2 (0.5 equiv.), stirring for 2 days (pptn); collection (filtration), drying (vac., over P2O5); elem. anal.;	56%

cobalt(II) chloride hexahydrate + Salicyluric acid (487-54-7) → Co(2+)*2C6H4(OH)CONHCH2COO(1-)*H2O*CH3OH=Co(C6H4(OH)CONHCH2COO)2*H2O*CH3OH

Conditions	Yield
With triethylamine In methanol addn. of Et3N (1 equiv.) to ligand, addn. to CoCl2 (0.5 equiv.), stirring for 24 h (pptn.); collection (filtration), drying (vac. over P2O5); elem. anal.;	53%

oxovanadium(IV) sulfate + Salicyluric acid (487-54-7) → VO(2+)*H(1+)*OC6H4C(O)NCH2COO(3-)*2H2O=VO(OC6H4C(O)NCH2COO)H(H2O)2

Conditions	Yield
With AcONa*3H2O; NaOH In ethanol; water N2-atmosphere; dropwise addn. of 1 equiv. VOSO4 to mixt. of ligand and AcONa (in 50% aq. EtOH), pH-adjustment to 4.5 (NaOH); standing for 1 week (pptn.), collection (filtration), washing (aq. EtOH), drying (vac.); elem. anal.;	40%

copper(II) perchlorate hexahydrate + Salicyluric acid (487-54-7) → Cu(3+)*C6H4(O)CONCH2COO(3-)*2H2O*CH3OH=CuC9H6NO4*2H2O*CH3OH

Conditions	Yield
With triethylamine In methanol addn. of Et3N (2 equiv.) into soln. of ligand, addn. to soln. of Cu(ClO4)2 (1 equiv.), stirring 6 h; collection (filtration), drying (60°C); elem. anal.;	35%

methanol (67-56-1) + Salicyluric acid (487-54-7) → salicyluric acid methyl ester (55493-89-5)

Conditions	Yield
With hydrogenchloride

Salicyluric acid (487-54-7) + furan-2,3,5(4H)-trione pyridine (1:1) → glycine (56-40-6) + salicylic acid (69-72-7)

Salicyluric acid (487-54-7) + acetic anhydride (108-24-7) + benzaldehyde (100-52-7) → 2-(2-acetoxy-phenyl)-4-((Z)-benzyliden)-4H-oxazol-5-one (16352-89-9)

Conditions	Yield
With sodium acetate

Upstream product

• 56145-98-3 N-Salicyloyl-glycin-amid 
• 856119-90-9 2-azidoacetoxy-benzoic acid 
• 116601-30-0 2-(N-benzyloxycarbonyl-glycyloxy)-benzoic acid benzyl ester 
• 27796-49-2 (2-methoxyphenyl)(methoxycarbonylmethylamino)-methanone 
• 61141-14-8 anionic phenyl salicylate 
• 56-40-6 glycine 
• 50331-25-4 (2,4-dioxo-4H-benzo[e][1,3]oxazin-3-yl)-acetic acid 
• 54539-61-6 2-hydroxybenzoyl azide 
• 55493-89-5 salicyluric acid methyl ester 
• 69-72-7 salicylic acid 
• 118-58-1 benzyl salicylate 
• 14216-34-3 2-methoxycarbonyloxy-benzoic acid 
• 579-75-9 2-Methoxybenzoic acid 
• 109-86-4 2-methoxy-ethanol 

Downstream Products

• 16352-96-8 2-(2-acetoxy-phenyl)-4-furfurylidene-4H-oxazol-5-one 
• 16352-94-6 2-(2-acetoxy-phenyl)-4-benzo[1,3]dioxol-5-ylmethylene-4H-oxazol-5-one 
• 56-40-6 glycine 
• 136492-94-9 N-salicyloyl-α-hydroxyglycine 
• 65-45-2 salicylamide 
• 69-72-7 salicylic acid 
• 118-79-6 2,4,6-tribromophenol 
• 1429128-83-5 N,N'-(2,2'-(2,2'-disulfanediylbis(ethane-2,1-diyl)bis(azanediyl))bis(2-oxoethane-2,1-diyl))bis(2-hydroxybenzamide) 
• 1258323-53-3 2-hydroxy-N-(2-oxo-2-(2-oxotetrahydrothiophen-3-ylamino)ethyl)benzamide 

Relevant articles and documents

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CHEMICAL COMPOUNDS

A compound which is a pyridine or isoquinoline derivative of formula (I), or a pharmaceutically acceptable salt thereof, which is useful in the inhibition of γ- butyrobetaine hydroxylase (BBOX). The compounds are particularly useful in treatment of cardio

Effects of mixed CH3CN - H2O solvents on rate of intramolecular general base-catalyzed cleavage of ionized phenyl salicylate in the presence of 3-aminopropan-1 -ol, 1,2-diaminoethane, and glycine

The effects of mixed CH3CN - H2O solvents on rates of aminolysis of ionized phenyl salicylate, PS-, reveal a nonlinear decrease in the nucleophilic second-order rate constants, knms. (for aminolysis) with increase in the content of CH3CN until it becomes ≈ 50%. v/v. The values of knms remain almost unchanged with change in the CH3CN content within 50 to 70 or 80%, v/v. The effects of mixed CH3CN - H2O solvents on pKa of leaving group, phenol, and protonated amine nucleophile have been concluded to be the major source for the ob- served mixed solvent effects on knms.