103-89-9

Basic information

• Product Name: p-Acetotoluidide
• Synonyms: N-(4-METHYLPHENYL)ACETAMIDE;N-ACETYL-P-TOLUIDINE;N-P-TOLYLACETAMIDE;P-ACETOTOLUIDIDE;P-ACETOTOLUIDINE;P-TOLYLACETAMIDE;P-METHYLACETANILDE;ACETYL-P-TOLUIDINE
• CAS NO: 103-89-9
• Molecular Formula: C₉H₁₁NO
• Molecular Weight: 149.19
• EINECS: 203-155-4
• Product Categories: Anilines, Amides & Amines;Aromatics;Miscellaneous Reagents
• Mol File: 103-89-9.mol
• Article Data: 410

Chemical Properties

• Melting Point: 149-151 °C(lit.)
• Boiling Point: 307 °C(lit.)
• Flash Point: 168 °C
• Appearance: Beige to light brown/Crystals or Crystalline Powder
• Density: 1.21
• Vapor Density: 5.14
• Refractive Index: 1.5279 (estimate)
• Storage Temp.: Store below +30°C.
• Solubility: 1.2g/l (experimental)
• PKA: 15.13±0.70(Predicted)
• Water Solubility: 1 g/L (25 ºC)
• Merck: 14,74
• BRN: 607036
• CAS DataBase Reference: p-Acetotoluidide(CAS DataBase Reference)
• NIST Chemistry Reference: p-Acetotoluidide(103-89-9)
• EPA Substance Registry System: p-Acetotoluidide(103-89-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: AN2930000
• TSCA: Yes
• Hazardous Substances Data: 103-89-9(Hazardous Substances Data)

Usage

Description

p-Acetotoluidide is an off-white to brown flake, odourless, solid or crystalline powder (pure form), which is soluble in hot water, alcohol, ether, chloroform, acetone, glycerol, and benzene. It is combustible and undergoes self-ignition (at 5450°C) but is otherwise stable under most conditions. p-Acetanilide on decomposition releases carbon monoxide, oxides of nitrogen, carbon dioxide, and toxic fumes. p-Acetanilide is used as an inhibitor of peroxides and stabiliser for cellulose ester varnishes. It is used as an intermediate for the synthesis of rubber accelerators, dyes and dye intermediate, and camphor. It is also used as a precursor in penicillin synthesis and other pharmaceuticals including painkillers and intermediates. Phenylacetamide structure shows analgesic and antipyretic effects. But acetanilide is not used directly for this application due to causing methemoglobinemia (the presence of excessive methemoglobin which does not function reversibly as an oxygen carrier in the blood).

Chemical Properties

Different sources of media describe the Chemical Properties of 103-89-9 differently. You can refer to the following data:
1. BEIGE TO LIGHT BROWN CRYSTALS OR CRYST. POWDER
2. p-Acetotoluidide is an off-white to brown fl ake, odorless, solid or crystalline powder (pure form), soluble in hot water alcohol, ether, chloroform, acetone, glycerol, and benzene. It is combustible and undergoes self-ignition (at 545°C), but is otherwise stable under most conditions. On decomposition, p-acetanilide releases carbon monoxide, oxides of nitrogen, carbon dioxide, and toxic fumes. p-Acetanilide is used as an inhibitor of peroxides and a stabilizer for cellulose ester varnishes. It is used as an intermediate for the synthesis of rubber accelerators, dyes and dye intermediate, and camphor. It is also used as a precursor in penicillin synthesis and other pharmaceuticals, including painkillers and intermediates. Phenylacetamide structure shows analgesic and antipyretic effects. But acetanilide is not used directly for this application because it causes methemoglobinemia (the presence of excessive methemoglobin that does not function reversibly as an oxygen carrier in the blood).

Uses

4′-Methylacetanilide was used in the synthesis of stable crystalline phosphorus ylides.

Synthesis Reference(s)

Journal of the American Chemical Society, 77, p. 5092, 1955 DOI: 10.1021/ja01624a042Organic Syntheses, Coll. Vol. 1, p. 111, 1941Synthesis, p. 118, 1977

General Description

Colorless needles.

Air & Water Reactions

Water insoluble.

Reactivity Profile

4'-Methylacetanilide is an amide. Flammable gases are formed by the reaction of organic amides 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).

Health Hazard

Different sources of media describe the Health Hazard of 103-89-9 differently. You can refer to the following data:
1. ACUTE/CHRONIC HAZARDS: When heated to decomposition 4'-Methylacetanilide emits toxic fumes.
2. Exposures to p-acetotoluidide through ingestion or inhalation cause potential health effects. The symptoms of toxicity include, but are not limited to, irritation to the eyes and redness of the skin, wheezing, cough, shortness of breath, or burning in the mouth, throat, or chest, and respiratory tract irritation.

Safety Profile

Moderately toxic by ingestion. See also ACETANILIDE. Combustible. When heated to decomposition it emits toxic fumes of NO,. To fight fire, use water, foam, CO2, dry chemical

storage

p-Acetanilide should be kept stored in a cool, dry place with the container closed when not in use

Purification Methods

Crystallise it from aqueous EtOH. [Beilstein 12 H 920, 12 I 420, 12 II 501, 12 III 2051, 12 IV 1902.]

Precautions

During handling and use of p-aetotoluidide, proper personal protective equipment should be worn. Avoid contact with the eyes, skin, and clothing. Avoid ingestion and inhalation. On accidental exposure at the workplace, workers should immediately fl ush the eyes and exposed part of the body with plenty of water. Workers should avoid using the contaminated clothing and shoes.

Upstream product

• 625-77-4 N-acetylacetamide 
• 540-23-8 p-toluidine hydrochloride 
• 108-24-7 acetic anhydride 
• 32954-54-4 para-methyl anilinium nitrate 
• 106-49-0 p-toluidine 
• 71-43-2 benzene 
• 621-01-2 N,N'-Bis(p-tolyl)thiourea 
• 60-35-5 acetamide 
• 50-78-2 aspirin 
• 86012-53-5 2,4-bis(p-methylanilino)-1,3-bis(p-methylphenyl)-1,3,2,4-diazadiphosphetidine 
• 64-19-7 acetic acid 
• 108-88-3 toluene 
• 16001-28-8 N-4-methylphenyl isocyanodichloride 
• 107-06-2 1,2-dichloro-ethane 

Downstream Products

• 18931-78-7 N-(2-chloro-4-methylphenyl)acetamide 
• 613-48-9 N,N-diethyl-p-toluidine 
• 63913-32-6 (5-acetylamino-2-methyl-phenyl)-chloro-acetic acid 
• 63913-33-7 acetic acid-[4-methyl-3-(1,2,2,2-tetrachloro-ethyl)-anilide] 
• 5132-17-2 N,N'-di(p-tolyl)acetamidine 
• 7472-91-5 4-methyl-diacetanilide 
• 100191-84-2 N-(prop-2-yn-1-yl)-N-(p-tolyl)acetamide 
• 10416-79-2 Trimethylsilylderivat von p-Methylacetanilid 
• 2941-71-1 2,6-dimethylbenzothiazole 
• 125781-67-1 1--1H-benzotriazole 
• 61305-66-6 2,4,6-trichloro-4-methyl-2,5-cyclohexadienone 
• 213615-72-6 N-Chloromethyl-N-p-tolyl-acetamide 
• 10557-67-2 N-nitroso-p-methyl-acetanilide 
• 612-45-3 4-methyl-2-nitroacetanilide 

Relevant articles and documents

Solvent free Beckmann rearrangement of ketoximes by anhydrous ferric chloride

Beckmann rearrangement of ketoximes is achieved efficiently by anhydrous FeCl3 in the absence of solvent. Unsymmetrical oximes are selectively produced one of the two possible products in good yields. Similar reactions are not occurred in the presence of solvent.

Study of 4-acetylaminotoluene ozonation in acetic acid

The reaction of 4-aminotoluene with ozone in acetic acid was studied. It was found that the reaction proceeds at a high rate, giving predominantly tars. The product composition changes after acylation of the amino group: aliphatic peroxides prevailed among the oxidation products and 4-acetylaminobenzoic acid was identified (16%) as well. It was shown that the presence of a catalyst (cobalt(II) acetate) had no substantial effect on the oxidation selectivity for the methyl group (32%) and only the addition of potassium bromide increased the activity of the catalyst; the yield of 4-acetylaminobenzoic acid reached 70%. The mechanism of oxidation in the presence of a cobalt-bromide catalyst explaining the obtained results was discussed.

Novel tetrazoloquinoline-thiazolidinone conjugates as possible antitubercular agents: Synthesis and molecular docking

A novel approach for the synthesis of a new 4-thiazolidinone scaffold was developed by a one-pot three-component cyclocondensation of various tetrazolo quinoline aldehydes 1a-f, acid hydrazide 2a-c, and thioglycolic acid 3 in the presence of [DBUH][OAc] as a catalyst in high yields. All the conjugates were screened for their antimycobacterial activity against MTB H37Ra and M. bovis BCG strains, with the MIC values ranging from 0.99-13.55 μmol mL-1 and 0.14-20.11 μmol mL-1, respectively. The 4-thiazolidinone-incorporated tetrazoloquinoline derivatives 4a, 4d, 4g, 4j, 4m, and 4p were highly potent against MTB H37Ra and M. bovis BCG strains. The most active compounds were also evaluated for their cytotoxicity against MCF-7, A549, and HCT 116 cell lines and were found to be non-cytotoxic. Further, molecular docking studies into the active site of the InhA enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping us to understand the ligand-protein binding interaction and establish a structural basis for the inhibition of mycobacterium tuberculosis. The results suggest that the tetrazoloquinoline-thiazolidinone conjugates 4a, 4d, 4g, 4j, 4m, and 4p are promising antitubercular agents.

Discovery and molecular docking of quinolyl-thienyl chalcones as anti-angiogenic agents targeting VEGFR-2 tyrosine kinase

Vascular endothelial growth factor Receptor-2 (VEGFR-2) kinase inhibition is one of the well established strategies to promptly tackle tumor growth by suppression of angiogenesis. In the current study, structure-based virtual screening methodology of a series of quinolyl-thienyl chalcones indicated their strong potential as VEGFR-2 kinase inhibitors. In vitro VEGFR-2 kinase inhibitory activity was found to be significant (compound 19, IC50: 73.41 nM). All compounds showed significant inhibition of human umbilical vein endothelial cells (HUVEC) proliferation (compound 19, IC50: 21.78 nM). Molecular interactions of the compounds were studied using molecular docking studies.

Paracetamol and other acetanilide analogs as inter-molecular hydrogen bonding assisted diamagnetic CEST MRI contrast agents

Paracetamol and a few other acetanilide derivatives are reported as a special class of diamagnetic Chemical Exchange Saturation Transfer (diaCEST) MRI contrast agents, that exhibit contrast only when the molecules form inter-molecular hydrogen bonding mediated molecular chains or sheets. Without the protection of the hydrogen bonding their contrast producing labile proton exchanges too quickly with the solvent to produce any appreciable contrast. Through a number of variable temperature experiments we demonstrate that under the conditions when the hydrogen bond network breaks and the high exchange returns back, the contrast drops quickly. The well-known analgesic drug paracetamol shows 12% contrast at a concentration of 15 mM at physiological conditions. With the proven safety track-record for human consumption and appreciable physiological contrast, paracetamol shows promise as a diaCEST agent forin vivostudies.

Novel tetrazoloquinoline-rhodanine conjugates: Highly efficient synthesis and biological evaluation

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 μg/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents.

Direct Photocatalytic Synthesis of Medium-Sized Lactams by C?C Bond Cleavage

Reported is a novel two-step ring-expansion strategy for expeditious synthesis of all ring sizes of synthetically challenging (hetero)aryl-fused medium-sized lactams from readily available 5–8-membered cyclic ketones. This step-economic approach features a remote radical (hetero)aryl migration from C to N under visible-light conditions. Broad substrate scope, good functional-group tolerance, high efficiency, and mild reaction conditions make this procedure very attractive. In addition, this method also provides expedient access to 13–15-membered macrolactams upon an additional one-step manipulation. Mechanistic studies indicate that the reaction involves an amidyl radical and is promoted by acid.

-

-

DNA interaction of bromomethyl-substituted acridines

A series of acridines with bifunctional substituents was synthesized with the dual properties of DNA alkylation and intercalation. 4,5-Bis(bromomethyl)acridine (1) was previously reported to crosslink and intercalate with DNA. In this study, 1,8-bis(bromomethyl)acridine (2) and 2,7-bis(bromomethyl)acridine (3), monofunctional 2-(bromomethyl)-7-methylacridine (4) and 2,7-dimethylacridine (5) were synthesized, and their crosslinking and intercalative activities were investigated to assess the reactivity of bromomethyl acridines with DNA. Interstrand crosslinking activity was similar among the three bis(bromomethyl)acridines. The acridines exhibited intercalation activity for calf thymus DNA as follows: 3 > 4 > 2 = 1 5. Intracellular DNA-crosslinking and DNA-intercalating activities were evaluated using the Ames assay. 4 was mutagenic in Salmonella typhimurium TA100 and TA98, indicating that the bromomethyl group alkylated DNA bases. All three bis(bromomethyl)acridines were mutagenic in S. typhimurium TA92 and TA94, which can detect intracellular crosslinking DNA damage, whereas 5 was not mutagenic in these strains. The results showed that the bis(bromomethyl)acridines crosslinked DNA and intercalated between DNA bases, and 3 exhibited the highest crosslinking and intercalating activity.

Synthesis of hippuric acid amides and coumarin derivatives. Effect of N,N-diethylacetamide

-

Palladium-catalyzed four-component carbonylative synthesis of 2,3-disubstituted quinazolin-4(3H)-ones: Convenient methaqualone preparation

A palladium-catalyzed four-component carbonylative cyclization reaction for the synthesis of 2,3-disubstituted quinazolin-4(3H)-ones has been developed. A range of different 2,3-disubstituted quinazolin-4(3H)-one derivatives were prepared in moderate to good yields employing simple and readily accessible 2-iodoanilines, nitro compounds and acid anhydrides as the synthetic precursors. Mo(CO)6 acted both as a solid CO source and a reductant. Notably, methaqualone as a sedative and hypnotic medication can be prepared easily in 68% yield (4b) under our conditions as well.

Synthesis and characterization of novel quinoline selenium compounds: X-ray structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline

A series of novel and synthetically important quinoline selenium compounds have been successfully synthesized using an efficient and simple strategy. The method employed leads to the synthesis of both cyclic as well as open chain quinoline selenium compounds. The prepared selenium compounds have been characterized with the help of various spectroscopic techniques viz., NMR (1H, 13C), FT-IR, mass spectrometry. The structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline has been determined by X-ray crystallography.

Visible-Light-Induced Oxidation of Diazenyl-Protected Tetrahydroisoquinolines and Isoindolines for the Synthesis of Functionalized Lactams

A visible-light-induced oxidation of diazenyl-protected tetrahydroisoquinolines and isoindolines for the synthesis of structurally diverse lactams is developed. The reaction was carried out with Eosin Y-Na2 as an organic photocatalyst and molecular oxygen as an oxidant, and the desired functionalized N-aryldiazenyl-lactams were obtained under mild and transition metal-free conditions. The utility of this method is showcased by the gram-scale synthesis and deprotection of the N-aryldiazenyl-lactam product. (Figure presented.).

Method for synthesizing amide derivative under catalysis of vanadium

The invention discloses a method for synthesizing an amide derivative under the catalysis of vanadium, which comprises the following step of: by using a nitro aromatic compound and an ester compound as raw materials, a vanadium compound as a catalyst and magnesium chips as a reducing agent, carrying out amidation reaction in an organic solvent to obtain the amide derivative. The method has the advantages that (1) the nitro aromatic compound which is good in stability, low in price and easy to obtain is used as a nitrogen source; (2) the used catalyst is cheap, easy to obtain and low in toxicity; and (3) the method has good substrate applicability, and is suitable for aromatic nitro compounds, fatty esters and aryl esters containing different substituents.

Method for catalyzing one-pot hydrogenation and amidation of nitroaromatic hydrocarbon and carboxylic acid by visible light

The invention discloses a method for catalyzing one-pot hydrogenation and amidation reaction of nitroaromatic hydrocarbon and carboxylic acid by visible light. The method comprises the following steps: preparing Pt nanoparticles uniformly dispersed on an N-doped titanium dioxide/titanium carbide (MXene) heterojunction as a photocatalyst (3% Pt/N-TiO2/Ti3C2), and applying the catalyst to a cascade reaction of an aromatic nitro compound and carboxylic acid to prepare an amide product. The 3% Pt/N-TiO2/Ti3C2 has excellent tandem hydrogenation and amidation activity and chemical selectivity of an aromatic nitro compound and carboxylic acid under the irradiation of visible light. The excellent catalytic performance of 3% Pt/N-TiO2/Ti3C2 is attributed to the close contact of TiO2 and conductive Ti3C2, and the separation efficiency of photo-induced electrons and holes is improved through charge short-range directional transmission. The preparation method of the catalyst is simple and easy to operate, the catalyst can be used for photocatalytic efficient one-pot hydrogenation and amidation reactions, the reaction conditions are mild, and the catalyst is easy to recycle.