65-45-2

Basic information

• Product Name: Salicylamide
• Synonyms: O-HYDROXYBENZAMIDE;Salamide;SALICYLAMIDE;2-Carbamoylphenol;2-hydroxy-benzamid;2-hydroxy-benzoicaciamide;Acket;Afko-Sal
• CAS NO: 65-45-2
• Molecular Formula: C₇H₇NO₂
• Molecular Weight: 137.14
• EINECS: 200-609-3
• Product Categories: AMIDE;Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;It is medicine of lever allaying and analgesia for lever,headache,neuralgia,joint ache and flexible rheumatism.;Amides;Building Blocks;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks;URTOSAL;Piperazines ,Oxazolines/Oxazolidines
• Mol File: 65-45-2.mol
• Article Data: 88

Chemical Properties

• Melting Point: 140-144 °C(lit.)
• Boiling Point: 270°C
• Flash Point: 181°C/14mm
• Appearance: White/Crystalline Powder
• Density: 1,175 g/cm3
• Vapor Pressure: 0.000195mmHg at 25°C
• Refractive Index: 1.5323 (estimate)
• Storage Temp.: Refrigerator
• Solubility: methanol: 0.1 g/mL, clear
• PKA: pKa 8.13(H2O t = 37) (Uncertain)
• Water Solubility: <0.1 g/100 mL at 20℃
• Stability: Stable. Light sensitive. Incompatible with strong bases, strong oxidizing agents.
• Merck: 14,8328
• BRN: 742439
• CAS DataBase Reference: Salicylamide(CAS DataBase Reference)
• NIST Chemistry Reference: Salicylamide(65-45-2)
• EPA Substance Registry System: Salicylamide(65-45-2)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 26-36
• RIDADR: 3249
• WGK Germany: 3
• RTECS: VN6475000
• TSCA: Yes
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 65-45-2(Hazardous Substances Data)

Usage

Chemical Description

Salicylamide is a white crystalline powder that is derived from salicylic acid and used as an analgesic and antipyretic.

Description

Salicylamide is less acidic (pKa 8.2) than other salicylic acid derivatives. Although poorly soluble in water, stable solutions can be formed at pH 9 through ionization of the phenolic group. It is absorbed from the GI tract on oral administration and is rapidly metabolized to inactive metabolites by intestinal mucosa, but not by hydrolysis. Activity appears to reside in the intact molecule. Salicylamide is approximately 40 to 55% plasma protein bound, and it competes with other salicylates and acetaminophen for glucuronide conjugation, decreasing the extent of conjugation of these other drugs.

Chemical Properties

white or light pink crystals or powder

Uses

Different sources of media describe the Uses of 65-45-2 differently. You can refer to the following data:
1. Medicine (analgesic).
2. salicylamide is an analgesic, fungicide, and anti-inflammatory ingredient used to soothe the skin. Salicylamide is an aromatic amide.
3. Salicylamide is used in combination with both aspirin and caffeine in the over-the-counter pain remedies. It is used as an analgesic and as an antipyretic.

Definition

ChEBI: The simplest member of the class of salicylamides derived from salicylic acid.

General Description

Different sources of media describe the General Description of 65-45-2 differently. You can refer to the following data:
1. Salicylamide, o-hydroxybenzamide, is a derivative of salicylicacid that is fairly stable to heat, light, and moisture. Itreportedly exerts a moderately quicker and deeper analgesiceffect than aspirin because of quicker CNS penetration. Its metabolismdiffers from aspirin, because it is not metabolized tosalicylic acid but rather excreted exclusively as the ether glucuronideor sulfate. Thus, as a result of lack of contributionfrom salicylic acid, it has a lower analgesic and antipyretic efficacythan that of aspirin. However, it can be used in place ofsalicylates for patients with a demonstrated sensitivity to salicylates.It is also excreted much more rapidly than other salicylates,which accounts for its lower toxicity. It is available inseveral nonprescription products, in combination with acetaminophenand phenyltoloxamine (e.g., Rid-A Pain compound,Cetazone T, Dolorex, Ed-Flex, Lobac) or with aspirin,acetaminophen, and caffeine (e.g., Saleto, BC Powder).
2. Odorless white or slightly pink crystals. Bitter taste, leaves a sensation of warmth on the tongue. pH (saturated aqueous solution at 82°F) about 5. Sublimation begins at the melting point.

Air & Water Reactions

Salicylamide darkens on exposure to air. . Insoluble in water.

Reactivity Profile

Salicylamide is an amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx). Salicylamide may be sensitive to prolonged exposure to light.

Fire Hazard

Flash point data for Salicylamide are not available; however, Salicylamide is probably combustible.

Clinical Use

Whereas salicylamide is reported to be as effective as aspirin as an analgetic/antipyretic and is effective in relieving pain associated with arthritic conditions, it does not appear to possess useful anti-inflammatory activity. Thus, indications for the treatment of arthritic disease states are unwarranted, and its use is restricted to the relief of minor aches and pain at a dosage of 325 to 650 mg three or four times per day. Its effects in humans are not reliable, however, and its use is not widely recommended.

Purification Methods

Crystallise the amide from water or repeatedly from CHCl3 [Nishiya et al. J Am Chem Soc 108 3880 1986]. [Beilstein 10 IV 169.] The anilide [87-17-2] M 213.2, m 135o crystallises from H2O. [Beilstein 12 H 500, 12 I 268, 12 II 256, 12 944.]

InChI:InChI=1/C7H7NO2/c8-7(10)5-3-1-2-4-6(5)9/h1-4,9H,(H2,8,10)

Synthetic route

2-ethyl-4-oxo-1,3-benzoxazinium perchlorate (56429-60-8) + 1,2-diamino-benzene (95-54-5) → 2-Ethyl-1H-benzoimidazole; compound with perchloric acid (138118-62-4) + salicylamide (65-45-2)

Conditions	Yield
at 100℃; for 0.0833333h;	A 100% B n/a

methyl thiosalicylate (17999-25-6) → salicylamide (65-45-2)

Conditions	Yield
With ammonia In dichloromethane at 20℃; for 6h;	100%

2-(cyclohex-2-enyloxy)-benzamide → salicylamide (65-45-2)

Conditions	Yield
With hydrogenchloride In diethyl ether at 20℃; for 0.0166667h;	98%

2-methyl-4-oxo-4H-benzo[e][1,3]oxazinium perchlorate (54789-70-7) + 1,2-diamino-benzene (95-54-5) → 2-(methyl)benzimidazolium perchlorate (1792-35-4) + salicylamide (65-45-2)

Conditions	Yield
at 100℃; for 0.0833333h; Product distribution; Mechanism; other 1,3-heterocyclic cations, other 1,4-binucleophiles;	A 97% B 96%
at 100℃; for 0.0833333h;	A 97% B 96%

methyl salicylate (119-36-8) → salicylamide (65-45-2)

Conditions	Yield
With ammonia In methanol at 50℃; for 16h; Sealed tube;	94%
With sodium metabisulfite; ammonium hydroxide at 40℃; for 8h; Reagent/catalyst; Temperature;	93.5%
With ammonia In aq. buffer at 45 - 50℃; under 760.051 Torr; for 1h; Reagent/catalyst; Temperature;	86.2%

salicylonitrile (611-20-1) → salicylamide (65-45-2)

Conditions	Yield
With water at 150℃; under 5171.62 - 6205.94 Torr; for 0.5h; Inert atmosphere; Microwave irradiation;	93%
With Acetaldehyde oxime; [(eta.(5)-pentamethylcyclopentadienyl)Rh(H2O)3](OTf)2 In water at 50℃; for 6h; Schlenk technique;	86%
With N-ethyl-N-hydroxy-ethanamine; water; copper diacetate In ethanol at 35℃; for 3h;	85%

N-(2,4-dimethoxybenzyl)-2-hydroxybenzamide → salicylamide (65-45-2)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 2h; Heating;	92%

salicylaldehyde (90-02-8) → salicylamide (65-45-2)

Conditions	Yield
With hydroxylamine hydrochloride In acetonitrile for 0.0652778h; Microwave irradiation;	92%
With hydroxylamine hydrochloride; methanesulfonyl chloride In neat (no solvent) at 70℃; for 3.5h;	91%
With triacetonitrile 4′-(4-chlorophenyl)-2,2′:6′,2″-terpyridine ruthenium(II) nitrate; hydroxylamine hydrochloride; sodium acetate In water at 100℃; for 12h; Inert atmosphere;	75%

2,2-dimethyl-4-(2-oxo-1H-pyrid-1-yl)oxy-2H-1,3-benzoxazine (74405-16-6) → 2-hydroxy-pyridine N-oxide (13161-30-3) + salicylamide (65-45-2)

Conditions	Yield
With hydrogenchloride for 3h; Product distribution; Ambient temperature;	A 90% B n/a

2-methyl-benzyl alcohol (89-95-2) → salicylamide (65-45-2)

Conditions	Yield
With aluminum oxide; hydroxylamine hydrochloride; methanesulfonyl chloride; water at 100℃; for 1h;	90%
With hydroxylamine hydrochloride; zinc(II) oxide at 140℃; for 2h; Beckmann rearrangement;	80%
With hydroxylamine hydrochloride; titanium(IV) oxide at 140℃; for 3h; Beckmann rearrangement;	80%
Stage #1: 2-methyl-benzyl alcohol With aluminum oxide; methanesulfonic acid at 100℃; Beckmann rearrangement; Stage #2: With hydroxylamine hydrochloride at 140℃; for 2.5h;	80 % Spectr.

salicylaldehyde-oxime (94-67-7) → salicylamide (65-45-2)

Conditions	Yield
With Cu(II) on nano silica functionalized triazine dendrimer In water at 20℃; for 0.8h; Beckmann Rearrangement; Green chemistry;	90%
With toluene-4-sulfonic acid; 1,2-bis-(diphenylphosphino)ethane; carbonyl(dihydro)tris(triphenylphosphine)ruthenium(II) In 1,4-dioxane Heating;	82%
With C82H80N4O6; mercury dichloride In tetrahydrofuran; water; toluene at 20℃; for 6.5h; Beckmann Rearrangement;	81%

2-(aminocarbonyl)benzeneboronic acid → salicylamide (65-45-2)

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 100℃; for 0.0833333h; Microwave irradiation; Green chemistry;	89%

benzamide (55-21-0) → salicylamide (65-45-2)

Conditions	Yield
With sodium persulfate; palladium diacetate In 1,4-dioxane at 80℃; for 16h; Inert atmosphere;	88%

2-(o-hydroxyphenyl)-4-oxo-1,3-benzoxazinium perchlorate (86245-83-2) + naphthalene-1,8-diamine (479-27-6) → 2-(1H-Perimidin-2-yl)-phenol; compound with perchloric acid (138118-68-0) + salicylamide (65-45-2)

Conditions	Yield
at 20℃; for 0.166667h;	A 86% B n/a

2-(benzyloxy)benzamide (29579-11-1) → salicylamide (65-45-2)

Conditions	Yield
With methyl-phenyl-thioether; trifluoroacetic acid In toluene at 20℃; for 24h;	83%

2-fluorobenzamide (445-28-3) → salicylamide (65-45-2)

Conditions	Yield
With water; potassium hydroxide In dimethyl sulfoxide at 20℃; for 16h;	83%

1,8-dimethylaminonaphthalene (20734-56-9) + 2-ethyl-4-oxo-1,3-benzoxazinium perchlorate (56429-60-8) → 1,3-dimethyl-2-ethylperimidinium perchlorate + salicylamide (65-45-2)

Conditions	Yield
at 80℃; for 4h;	A 77% B 82%

salicylonitrile (611-20-1) → salicylamide (65-45-2) + salicylic acid (69-72-7)

Conditions	Yield
With phosphate buffer at 30℃; for 3h; rhodococcus rhodocrous AJ270, pH 7.0;	A 80% B 5%
With potassium phosphate buffer at 30℃; for 3h; Rhodococcus sp. AJ270 cells;	A 80.1% B 5%

2-styryl-1,3-benzoxazinonium perchlorate (56429-66-4) + naphthalene-1,8-diamine (479-27-6) → 2-((E)-Styryl)-1H-perimidine; compound with perchloric acid (138118-67-9) + salicylamide (65-45-2)

Conditions	Yield
at 80℃; for 0.0666667h;	A 80% B n/a

hydroxybenzaldoxime (22032-06-0) → salicylamide (65-45-2)

Conditions	Yield
With aluminum oxide; methanesulfonic acid at 140℃; for 2.5h; Beckmann rearrangement;	80%
With cerium(III) chloride; silica gel; sodium iodide for 0.1h; Beckmann rearrangement; microwave irradiation;	79%

2-Iodophenol (533-58-4) + carbon monoxide (201230-82-2) → salicylamide (65-45-2)

Conditions	Yield
With 1H-imidazole; ammonium carbamate; triethylamine In N,N-dimethyl-formamide at 130℃; for 12h; Sealed tube;	80%

1-cyanobenzene oxide-oxepin (73654-43-0) → salicylonitrile (611-20-1) + salicylamide (65-45-2) + phenol (108-95-2)

Conditions	Yield
In tetrahydrofuran; water for 48h; Heating; pH=7;	A 75% B 18% C 7%

2-methoxybenzamide (2439-77-2) → salicylamide (65-45-2)

Conditions	Yield
With piperazine In N,N-dimethyl acetamide at 150℃; for 8h; Substitution; Demethylation;	74%

salicylic acid (69-72-7) → salicylamide (65-45-2)

Conditions	Yield
With zirconium(IV) oxychloride; urea at 80℃; for 0.0111111h; Sealed tube; Microwave irradiation;	73%
With ammonium carbonate; ortho-tungstic acid; zinc(II) oxide In 5,5-dimethyl-1,3-cyclohexadiene at 160℃; for 8h;	73.7%
With pyridine; urea for 0.00555556h; microwave irradiation;	70%

2-methyl-4-oxo-4H-benzo[e][1,3]oxazinium perchlorate (54789-70-7) + 1,2-(N,N'-dimethyl)-5-triphenylmethylphenylenediamine (138118-61-3) → 1,3-(N,N'-dimethyl)-2-methyl-5-triphenylmethylbenzimidazolium perchlorate + salicylamide (65-45-2)

Conditions	Yield
at 120℃; for 0.25h;	A 71% B n/a

2-methyl-4-oxo-4H-benzo[e][1,3]oxazinium perchlorate (54789-70-7) + 2-amino-4-methyl-N-methylaminobenzene (39513-19-4) → 1,2,5-trimethylbenzimidazolium perchlorate + salicylamide (65-45-2)

Conditions	Yield
at 100℃; for 0.0833333h;	A 63% B n/a

salicylhydroxamic acid (89-73-6) → salicylaldehyde (90-02-8) + salicylamide (65-45-2)

Conditions	Yield
With samarium diiodide; phosphoric acid In tetrahydrofuran; methanol for 0.000833333h; Ambient temperature;	A 59% B 40%

2-Bromobenzamide (4001-73-4) → salicylamide (65-45-2)

Conditions	Yield
With oxygen; triethylamine; sodium iodide In acetonitrile at 32℃; for 24h; Schlenk technique; UV-irradiation;	59%

2-methyl-4-oxo-4H-benzo[e][1,3]oxazinium perchlorate (54789-70-7) + naphthalene-1,8-diamine (479-27-6) → 2-Methyl-1H-perimidine; compound with perchloric acid (138118-66-8) + salicylamide (65-45-2)

Conditions	Yield
at 80℃; for 0.0666667h;	A 56% B n/a

Upstream product

• 2037-95-8 1,3-benzoxazine-2,4-dione 
• 62-53-3 aniline 
• 20602-57-7 2-methyl-2,3-dihydro-4H-1,3-benzoxazin-4-one 
• 91132-80-8 2-isopropyl-2,3-dihydro-4H-benzo[e][1,3]oxazin-4-one 
• 6629-80-7 2-Phenyl-2,3-dihydro-benzo[e][1,3]oxazin-4-one 
• 21013-96-7 (E)-2-hydroxylbenzaldehyde oxime 
• 5663-71-8 O-acetylsalicylamide 
• 861514-80-9 2-hydroxy-N-(2-methoxybenzoyl)benzamide 
• 952008-51-4 dibenzoyl-(2-benzoyloxy-benzoyl)-amine 
• 94-67-7 salicylaldehyde-oxime 
• 75-36-5 acetyl chloride 
• 197236-85-4 2-phenylcarbamoyloxy-benzoic acid amide 
• 57-13-6 urea 
• 69-72-7 salicylic acid 

Downstream Products

• 1144-30-5 2-hydroxy-N-piperidin-1-ylmethyl-benzamide 
• 17357-04-9 2-hydroxy-N-morpholin-4-ylmethyl-benzamide 
• 13316-79-5 O-Benzoylsalicylamide 
• 132305-19-2 benzoyl-(2-benzoyloxy-benzoyl)-amine 
• 5663-74-1 N-benzoylsalicylamide 
• 5663-71-8 O-acetylsalicylamide 
• 611-20-1 salicylonitrile 
• 2037-95-8 1,3-benzoxazine-2,4-dione 
• 103204-34-8 3-(2-carbamoyl-phenoxy)-propionic acid 
• 25238-94-2 2-(2,3-dihydroxy-propoxy)-benzoic acid amide 
• 99060-46-5 O-propionyl salicylamide 
• 487-48-9 salacetamide 
• 29579-11-1 2-(benzyloxy)benzamide 
• 681851-72-9 2-(2-chlorophenyl)-2,3-dihydrobenzo[e][1,3]oxazin-4-one 

Relevant articles and documents

Copper-mediated α-hydroxylation of N-salicyloyl-glycine. A model for peptidyl-glycine α-amidating monooxygenase (PAM)

Title compound 1 is selectively hydroxytated in α position by three distinct copper- containing oxidant systems, involving dioxygen, peroxide anion or trimethylamine oxide. Trivalent copper is likely the key intermediate in this first reported model for the PHM activity of enzyme PAM.

Efficient nitriding reagent and application thereof

The invention discloses an efficient nitriding reagent and application thereof, wherein the nitriding reagent comprises nitrogen oxide, an active agent, a reducing agent and an organic solvent. By applying the nitriding reagent, nitrogen-containing compounds such as amide, nitrile and the like can be produced, and the method is simple in condition, low in waste discharge amount and simple in reaction equipment.

Application method of antioxidant in salicylamide synthesis process

The invention discloses an application method of an antioxidant in a salicylamide synthesis process, wherein the application method comprises the steps: in the process of synthesizing salicylamide from methyl salicylate, adding the antioxidant, and after reaction is completed, carrying out after-treatment to obtain a finished product white salicylamide. The raw materials of the antioxidant are cheap and easily available; the method has the advantages of simple process, energy conservation, consumption reduction, high production safety and the like; the problem that the color of salicylamide isslightly pink in the existing industrial production is solved; the step of crude product purification is omitted; and the product quality and yield are greatly improved.

Preparation method of aromatic amide compound

The present invention provides a preparation method of an aromatic amide compound. In an organic solvent, under the effect of a catalyst, an aromatic acid compound and an amine source are subjected toa dehydration reaction to obtain the aromatic amide compound, wherein the aromatic acid compound is an aromatic acid, a substituted aromatic acid, a heterocyclic aromatic acid or a substituted heterocyclic aromatic acid; and the substituent group of amide is any substituent group of H, a C1-C8 straight-chain alkyl or branched-chain alkyl group, a benzene ring or an aromatic ring. The aromatic amide compound is an important chemical intermediate, and the synthesis method is mild in reaction condition and high in yield.