85-91-6

Usage

Uses

Used in Flavor Industry:
Methyl 2-(methylamino)benzoate is used as a flavorant in a wide range of foods, particularly flour and sugar confections. Its unique aroma and flavor profile make it a valuable ingredient in creating distinct and appealing taste experiences for consumers.
Used in Food Industry:
Methyl 2-(methylamino)benzoate is one of many volatile components found in mango cultivars. Its presence contributes to the overall aroma and flavor profile of mangoes, enhancing their natural taste and making them more appealing to consumers.

Preparation

By methylation of methyl anthranilate or esterification of N-methylanthranillic acid.

Production Methods

Methyl N-methanthranilate is a component of mandarin and mandarin tree leaf essential oil. It is also found in oil from bulbs of Kaempferia ethelae L., hyacinth flowers, and orange petitgrain . It is synthesized by methylation of methyl anthranilate or esterification ofN-methylanthranilic acid.

Synthesis Reference(s)

The Journal of Organic Chemistry, 49, p. 3373, 1984 DOI: 10.1021/jo00192a024

Toxicity evaluation

The acute oral LD50 value in rats was reported as 3.7 ml/kg (Levenstein, 1974). The acute oral LD50 in female rats was reported to be between 2.25 g/kg (no deaths) and 3.38 g/kg (100% deaths) (Gaunt, Sharratt, Grasso & Wright, 1970). The acute dermal LD50 value in rabbits was reported as > 5 g/kg (Levenstein, 1974). The LC 50 for larvae of Tribolium destructor was found to be 0-1151 mg/cm3 (Vasechko, Kuznetsov, Smelyanets & Guznenok, 1970).

Safety Profile

Poison by intravenous route. Moderately toxic by ingestion. Combustible liquid. When heated to decomposition it emits toxic fumes of NOx. See also ESTERS.

Upstream product

• 67-56-1 methanol 
• 119-68-6 N-Methylanthranilic acid 
• 10328-92-4 N-Methylisatoic anhydride 
• 134-20-3 2-carbomethoxyaniline 
• 74-88-4 methyl iodide 
• 37960-65-9 potassium anthranilate 
• 118-92-3 anthranilic acid 
• 77-78-1 dimethyl sulfate 
• 127903-05-3 N-methyl-N-(2-methoxycarbonylphenyl)sulfuric diamide 
• 91157-34-5 Dimethyl 2-(N-tert-butyl-N-methylamino)benzoylphosphonate 
• 90578-35-1 avenestergenin A-1 
• 118-48-9 isatoic anhydride 
• 39650-82-3 2,2-dimethoxy-1-methylpyrrolidine 
• 33923-02-3 methyl N-methyl-N-carbethoxyanthranilate 

Downstream Products

• 526-43-2 N²-2-methylaminobenzoyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-one 
• 100609-70-9 N-butyryl-N-methyl-anthranilic acid methyl ester 
• 63923-69-3 N-ethyl-N-methyl-anthranilic acid methyl ester 
• 730970-91-9 N-methyl-N-(2-nitro-benzoyl)-anthranilic acid methyl ester 
• 52479-65-9 1-(2-methylaminobenzoyl)hydrazine 
• 68061-82-5 methyl 2-(methyl(nitroso)amino)benzoate 
• 55212-26-5 1-methyl-3-(3-trifluoromethyl-anilinomethyl)-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one 
• 88263-82-5 1-Methyl-3-(2-methylamino-benzoyl)-pyrrolidinon-2 
• 88263-83-6 1-Phenyl-3-(2-methylamino-benzoyl)-pyrrolidinon-2 
• 75541-61-6 2-(benzoyl-methylamino)benzoic acid methyl ester 
• 5946-42-9 methyl 2-(N-bromoacetyl-N-methylamino)benzoate 
• 719-54-0 10-methyl-9, 10-dihydro-9-acridinone 
• 57513-54-9 ethyl 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate 
• 29055-08-1 N-methyl-o-aminobenzyl alcohol 

Relevant academic research and scientific papers

Tunable Electrosynthesis of Anthranilic Acid Derivatives via a C-C Bond Cleavage of Isatins

A facile and direct electrocatalytic C-C bond cleavage/functionalization reaction of isatins was developed. With isatins as the amino-attached C1 sources, a variety of aminobenzoates, and aminobenzamides were synthesized in moderate to good yields under mild conditions.

A novel pathway for the thermolysis of N-nitrosoanthranilates using flash vacuum pyrolysis leading to 7-aminophthalides

Flash vacuum pyrolysis of methyl N-methyl-N-nitrosoanthranilate leads to elimination of nitric oxide and disproportionation of the formed N-radical to 7-(methylamino)phthalide and methyl N-methylanthranilate. This transformation was found to be a convenient, solvent-free method for the preparation of 7-(methylamino)phthalides. An alternative route through pyrolysis of N-benzyl-N-methyl anthranilates was also investigated. This journal is

Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer

Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.

PYRIMIDINE SEVEN-MEMBERED-RING COMPOUNDS, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF, AND USES THEREOF

The present invention relates to compounds (I) capable of inhibiting the Mstl/2 protein kinase activity, a preparation method therefor, a pharmaceutical composition comprising the compounds, and uses of the compounds and the pharmaceutical composition comprising the compounds in the preparation of drugs for prompting repair and regeneration of tissues and organs, prompting stem cell proliferation and somatic cell dedifferentiation, immunosuppression, and preventing or treating diseases related to nervous disorders and local ischemia.

Chemoselectivity for Alkene Cleavage by Palladium-Catalyzed Intramolecular Diazo Group Transfer from Azide to Alkene

Alkenes can be cleaved by means of the (3+2) cycloaddition and subsequent cycloreversion of 1,3-dipoles, classically ozone (O3), but the azide (R?N3) variant is rare. Chemoselectivity for these azide to alkene diazo group transfers (DGT) is typically disfavored, thus limiting their synthetic utility. Herein, this work discloses a palladium-catalyzed intramolecular azide to alkene DGT, which grants chemoselectivity over competing aziridination. The data support a catalytic cycloreversion mechanism distinct from other known metal-catalyzed azide/alkene reactions: nitrenoid/metalloradical and (3+2) cycloadditions. Kinetics experiments reveal an unusual mechanistic profile in which the catalyst is not operative during the rate-controlling step, rather, it is active during the product-determining step. Catalytic DGT was used to synthesize N-heterocyclic quinazolinones, a medicinally relevant structural core. We also report on the competing aziridination and subsequent ring expansion to another N-heterocyclic core structure of interest, benzodiazepinones.

Halogen-substituted anthranilic acid derivatives provide a novel chemical platform for androgen receptor antagonists

Androgen receptor (AR) antagonists are used for hormone therapy of prostate cancer (PCa). However resistance to the treatment occurs eventually. One possible reason is the occurrence of AR mutations that prevent inhibition of AR-mediated transactivation by antagonists. To offer in future more options to inhibit AR signaling, novel chemical lead structures for new AR antagonists would be beneficial. Here we analyzed structure-activity relationships of a battery of 36 non-steroidal structural variants of methyl anthranilate including 23 synthesized compounds. We identified structural requirements that lead to more potent AR antagonists. Specific compounds inhibit the transactivation of wild-type AR as well as AR mutants that render treatment resistance to hydroxyflutamide, bicalutamide and the second-generation AR antagonist enzalutamide. This suggests a distinct mode of inhibiting the AR compared to the clinically used compounds. Competition assays suggest binding of these compounds to the AR ligand binding domain and inhibit PCa cell proliferation. Moreover, active compounds induce cellular senescence despite inhibition of AR-mediated transactivation indicating a transactivation-independent AR-pathway. In line with this, fluorescence resonance after photobleaching (FRAP) - assays reveal higher mobility of the AR in the cell nuclei. Mechanistically, fluorescence resonance energy transfer (FRET) - assays indicate that the amino-carboxy (N/C)-interaction of the AR is not affected, which is in contrast to known AR-antagonists. This suggests a mechanistically novel mode of AR-antagonism. Together, these findings indicate the identification of a novel chemical platform as a new lead structure that extends the diversity of known AR antagonists and possesses a distinct mode of antagonizing AR-function.

Acetylhydrazone-based compounds and preparation method thereof

The invention discloses acetylhydrazone-based compounds and a preparation method thereof. The acetylhydrazone-based compounds are 2-(1-methyl-6-chloro-2,4 (1H, 3H)-quinazolinedione) acetylhydrazone-based compounds expressed by a general formula I. In-vitro antimicrobial activity tests find that the acetylhydrazone-based compounds have certain inhibitory activity on gram-positive bacteria (staphylococcus aureus, methicillin-resistant staphylococcus aureus and bacillus subtilis), gram-negative bacteria (escherichia coli, proteusbacillus vulgaris and pseudomonas aeruginosa), and fungi (candida albicans, aspergillus flavus, aspergillus fumigatus and cryptococcus neoformans), and some compounds have the inhibitory activity on some tested strains that is close and even prior to the inhibitory activity of the existing drug streptomycin sulfate polyoxin B, so that the compounds can be used for preparing antibacterial and/or antifungal drugs. The preparation method for the compounds is simple, the raw materials are easily available, and the cost is relatively low.

Investigation into the stability and reactivity of the pentacyclic alkaloid dehydroevodiamine and the benz-analog thereof

Limited synthetic approaches to obtain the biologically active alkaloid dehydroevodiamine (DHED) are known to date. Undesired demethylation in the most widely applied route was found to be a hampering side reaction for the benz-DHED derivative leading to a quinazolinone, which represents a benz-rutaecarpine derivative. For rutaecarpine, a related plant alkaloid, many different synthetic approaches have been described. Alternative reaction procedures to obtain DHED such as methylation of rutaecarpine and oxidation of evodiamine were investigated to make DHED more easily accessible and the latter method proved to be the most successful one. Furthermore, the remarkable equilibrium between the ring closed quinazolinium and the ring open form of the compounds was systematically investigated by UV-vis measurements. The ring open form and the quinazolinium salt, form the same species when incubated in buffer solution for 24 h. A better soluble form, i.e., 'hydroxyevodiamine', seems to represent the biologically active form that has not yet been described.

Indolo hexahydropyrazino quinazolinones anti-tumor compound and its preparation method

The invention relates to the technical field of medicines and in particular relates to indol-hexahydropyrazine-quinazolinone anti-tumour compounds and a preparation method thereof. A chemical structural formula of the indol-hexahydropyrazine-quinazolinone anti-tumour compounds is shown in a genera formula I or a genera formula II, the indol-hexahydropyrazine-quinazolinone anti-tumour compounds are evodiamine new skeleton compounds obtained by carrying out systematic skeleton transition design and synthesis on evodiamine, are newfound topoisomerase I/microtubulin dual inhibitors with a brand new structure and have obvious anti-tumour activity. The invention also provides application of the indol-hexahydropyrazine-quinazolinone anti-tumour compounds in preparation of topoisomerase I/microtubulin dual inhibitors and antitumour drug. The general formula (I) and the general formula (II) are described in the specification.

Copper-Catalyzed O-Methylation of Carboxylic Acids Using DMSO as a Methyl Source

A copper-catalyzed O-methylation of carboxylic acids using dimethyl sulfoxide (DMSO) as the methyl source is disclosed. This transformation exhibits a broad substrate scope and excellent functional group tolerance. Mechanistic studies indicate that a methyl radical is generated from dimethyl sulfoxide in the reaction process.