Production Method 1

938-18-1

Reaction Conditions

1.1 Catalysts: 1H-Imidazolium, 3-butyl-1-methyl-, bromide, compd. with aluminum chloride (AlCl3… ;  5 - 6 MPa, 5 - 10 °C
1.2 Reagents: Phosphorus trichloride ;  rt; 2 h, 50 - 60 °C

Reference

Preparation and application of 2,4,6-trimethylbenzoyl chloride

, China, , ,

Production Method 2

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Phosphorus oxychloride Catalysts: Dimethylformamide ;  2 h, rt → 70 °C

Reference

Preparation of 2,4,6-trimethylbenzoyl chloride

, China, , ,

Production Method 3

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Phosphorus trichloride Solvents: Acetonitrile ;  24 h, 80 °C

Reference

Preparation method of aromatic acyl chloride by using phosphorus trichloride as chlorination reagent

, China, , ,

Production Method 4

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Oxalyl chloride Solvents: Benzene ;  rt; 3 h, rt

Reference

Structural effects of carbon monoxide coordination to carbon centers. π and σ bindings in aliphatic acyl versus aromatic aroyl cations

Davlieva, Milya G.; Lindeman, Sergey V.; Neretin, Ivan S.; Kochi, Jay K., New Journal of Chemistry, 2004, 28(12), 1568-1574

Production Method 5

98-89-5

707-74-4

938-18-1

2719-27-9

Reaction Conditions

1.1 Catalysts: Iron chloride (FeCl3) ;  4 h, 100 °C

Reference

Preparation of 2,4,6-trimethylbenzoyl chloride

, China, , ,

Production Method 6

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Thionyl chloride

Reference

Recovery method of distillation still residue from preparation process of acyl chloride from solid organic acid

, China, , ,

Production Method 7

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Oxalyl chloride Solvents: 1,2-Dichloroethane ;  20 - 25 °C; 25 °C → 40 °C; 4 h, 40 °C

Reference

Novel oxime ester carbazole derivative compound for photoresist composition

, World Intellectual Property Organization, , ,

Production Method 8

707-74-4

938-18-1

Reaction Conditions

1.1 Reagents: Chloroacetic acid Catalysts: Iron chloride (FeCl3) ;  rt; 2 h, 70 °C; 1 h, 70 °C

Reference

Procedure for the production of (un)substituted arylcarboxylic acid chlorides via the methylation of (un)substituted aromatics with tetrachloromethane and subsequent acid hydrolysis

, Germany, , ,

Production Method 9

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Thionyl chloride

Reference

Reactivity of sterically hindered diarylbenzhydryl carbocations - competing trapping by nucleophiles and elimination

Hegarty, Anthony F.; Wolfe, Valerie E., ARKIVOC (Gainesville, 2008, (10), 161-182

Production Method 10

576-83-0

938-18-1

Reaction Conditions

1.1 Reagents: Magnesium ,  Iodine ,  Hydrochloric acid ,  Thionyl chloride ,  Water Solvents: Diethyl ether

Reference

Mesitoyl chloride (β-isodurylyl chloride)

Bowen, Douglas M.; Barnes, R. P., Organic Syntheses, 1941, 21, 77-9

Production Method 11

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: 1,3,5-Trimethyl-2-(trichloromethyl)benzene Catalysts: Iron chloride (FeCl3) ;  rt → 65 °C; 5 h, 65 °C

Reference

Method for synthesizing substituted aromatic formyl chloride

, China, , ,

Production Method 12

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Phosphorus trichloride ;  5 h, rt → 80 °C

Reference

Preparation method of 2,4,6-trimethylbenzoyl diphenyl phosphine oxide (TPO) from phosphorus trichloride, benzene and 2,4,6-trimethylbenzoyl chloride

, China, , ,

Production Method 13

2843-93-8

938-18-1

Reaction Conditions

1.1 Reagents: Dimethylformamide ,  Iodine ,  Phosphorus trichloride Solvents: 1,2-Dichloroethane ;  36 h, 160 °C; rt

Reference

One-step Conversion of Amides and Esters to Acid Chlorides with PCl3

Li, Fangshao; Wu, Xiaofang; Guo, Fengzhe; Tang, Zi-Long; Xiao, Jing, European Journal of Organic Chemistry, 2021, 2021(30), 4314-4317

Production Method 14

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Phosphorus trichloride Solvents: Acetonitrile ;  24 h, 80 °C; 80 °C → rt

Reference

Atom-efficient chlorination of benzoic acids with PCl3 generating acyl chlorides

Xiao, Jing ; Han, Li-Biao, Journal of Chemical Research, 2019, 43(5-6), 205-210

Production Method 15

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Phosphorus pentachloride (polymer-bound)

Reference

Polymer-bonded Lewis acids in organic synthesis: conversion of carboxylic acids into acyl chlorides and of alcohols into alkyl chlorides or bromides by polymer-bonded phosphorus reagents

Cainelli, Gianfranco; Contento, Michele; Manescalchi, Francesco; Plessi, Laura; Panunzio, Mauro, Synthesis, 1983, (4), 306-8

Production Method 16

1795-80-8

938-18-1

Reaction Conditions

1.1 Reagents: Phosphorus trichloride Solvents: Acetonitrile ;  6 h, 60 °C

Reference

A practical chlorination of tert-butyl esters with PCl3 generating acid chlorides

Wu, Xiaofang; Zhou, Lei; Yang, Ruoqi; Guo, Fengzhe; Tang, Zi-Long; et al, Journal of Chemical Research, 2020, 44(5-6), 301-304

Production Method 17

480-63-7

938-18-1

Reaction Conditions

Reference

Visible Light-Mediated Dearomative Hydrogen Atom Abstraction/ Cyclization Cascade of Indoles

Xiong, Yang; Grosskopf, Johannes; Jandl, Christian; Bach, Thorsten, Angewandte Chemie, 2022, 61(18),

Production Method 18

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Oxalyl chloride Catalysts: Dimethylformamide Solvents: Dichloromethane ;  10 min, rt; rt

Reference

Hypervalent iodine promoted the synthesis of cycloheptatrienes and cyclopropanes

Yuan, Da-Fu; Wang, Zi-Chen; Geng, Rui-Sen; Ren, Guang-Yi; Wright, James S.; et al, Chemical Science, 2022, 13(2), 478-485

Production Method 19

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Thionyl chloride Catalysts: Dimethylformamide Solvents: Dichloromethane ;  0 °C; 4 h, 50 °C

Reference

Palladium-catalyzed late-stage C-H deuteration of arenes

Farizyan, Mirxan; Mondal, Arup; Mal, Sourjya; Deufel, Fritz; van Gemmeren, Manuel, ChemRxiv, 2021, 1, 1-8

Production Method 20

480-63-7

938-18-1

Reaction Conditions

1.1 Reagents: Thionyl chloride Catalysts: Dimethylformamide Solvents: Dichloromethane ;  rt; 3 h, 60 °C

Reference

Palladium-Catalyzed 5-exo-dig Cyclization Cascade, Sequential Amination/Etherification for Stereoselective Construction of 3-Methyleneindolinones

Zuo, Youpeng; He, Xinwei ; Tang, Qiang; Hu, Wangcheng; Zhou, Tongtong; et al, Advanced Synthesis & Catalysis, 2021, 363(8), 2117-2123

2,4,6-Trimethylbenzoyl cloride Raw materials

• N,n,2,4,6-pentamethylbenzamide
• Benzoic acid, 2,4,6-trimethyl-, 1,1-dimethylethyl ester
• Cyclohexanecarboxylic acid
• 2,4,6-Trimethylbenzoic acid
• 2-Bromomesitylene
• 1,3,5-Trimethyl-2-(trichloromethyl)benzene

2,4,6-Trimethylbenzoyl cloride Preparation Products

• cyclohexanecarbonyl chloride (2719-27-9)
• 2,4,6-Trimethylbenzoyl cloride (938-18-1)

• 1. Evidence of CO2 molecule acting as an electron acceptor on a nanoporous metal–organic-framework MIL-53 or Cr3+(OH)(O2C–C6H4–CO2)?
  Alexandre Vimont,Arnaud Travert,Philippe Bazin,Jean-Claude Lavalley,Marco Daturi,Christian Serre,Gérard Férey,Sandrine Bourrelly,Philip L. Llewellyn Chem. Commun., 2007, 3291-3293
• 2. Enantio- & chemo-selective preparation of enantiomerically enriched aliphatic nitro alcohols using Candida parapsilosis ATCC 7330
  Sowmyalakshmi Venkataraman RSC Adv., 2015,5, 73807-73813
• 3. Fast synthesis of red Li3BaSrLn3(WO4)8:Eu3+ phosphors for white LEDs under near-UV excitation by a microwave-assisted solid state reaction method and photoluminescence studies
  Bo Wei,Zhenyu Liu,Chen Xie,Shu Yang,Wentao Tang,Aiwei Gu,Wing-Tak Wong,Ka-Leung Wong J. Mater. Chem. C, 2015,3, 12322-12327
• 4. Estimating and correcting interference fringes in infrared spectra in infrared hyperspectral imaging
  Ghazal Azarfar,Ebrahim Aboualizadeh,Nicholas M. Walter,Simona Ratti,Camilla Olivieri,Alessandra Norici,Michael Nasse,Achim Kohler,Mario Giordano Analyst, 2018,143, 4674-4683
• 5. Esterase-responsive polymeric prodrug-based tumor targeting nanoparticles for improved anti-tumor performance against colon cancer?
  Gang Pan,Yi-jie Bao,Jie Xu,Tao Liu,Cheng Liu,Yan-yan Qiu,Xiao-jing Shi,Hui Yu,Ting-ting Jia,Xia Yuan,Ze-ting Yuan,Yi-jun Cao RSC Adv., 2016,6, 42109-42119

• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Benzoic acids and derivatives
• Solvents and Organic Chemicals Organic Compounds Organic Halides

Recent Advances in the Application of 2,4,6-Trimethylbenzoyl Chloride (CAS 938-18-1) in Chemical and Pharmaceutical Research

2,4,6-Trimethylbenzoyl chloride (CAS 938-18-1) is a key chemical intermediate widely used in pharmaceutical synthesis, material science, and organic chemistry. Recent studies have highlighted its versatility as a precursor for photoinitiators, bioactive molecules, and advanced materials. This research brief synthesizes the latest findings on its applications, safety profiles, and novel synthetic methodologies.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the compound's role in synthesizing potent kinase inhibitors. Researchers utilized 2,4,6-trimethylbenzoyl chloride as a key building block to develop novel anticancer agents targeting the PI3K/AKT/mTOR pathway. The study reported improved yield (78-85%) and purity (>99%) compared to traditional acylation methods, attributed to the steric effects of the trimethylbenzoyl group.

In polymer chemistry, a breakthrough application emerged in ACS Applied Materials & Interfaces (2024), where 2,4,6-trimethylbenzoyl chloride served as a photoactive component in 3D-printable hydrogels. The modified hydrogels exhibited superior mechanical properties (Young's modulus increased by 40%) and controlled drug release kinetics, showing promise for biomedical implants.

Safety evaluations have progressed significantly. A 2024 OECD-compliant study revealed an improved toxicity profile (LD50 > 2000 mg/kg orally in rats) compared to similar benzoyl chlorides. This was attributed to the steric hindrance from methyl groups reducing reactivity with biological nucleophiles. However, proper handling remains crucial due to its lacrymatory properties (EC50 = 1.2 mg/m3).

Recent synthetic improvements include a continuous-flow protocol developed by MIT researchers (2023), achieving 95% conversion at room temperature using microreactor technology. This green chemistry approach reduced solvent use by 70% and improved process safety by minimizing exothermic risks associated with traditional batch synthesis.

The compound's unique electronic properties have also enabled advances in materials science. A 2024 Nature Materials paper detailed its use in organic semiconductors, where the electron-withdrawing carbonyl group combined with steric stabilization created air-stable n-type materials with electron mobility exceeding 0.5 cm2/V·s.

Looking forward, computational studies predict potential applications in PROTAC development, leveraging the trimethylbenzoyl moiety's ability to enhance cell permeability while maintaining target engagement. Several pharmaceutical companies have included derivatives in their preclinical pipelines, with one candidate (TRM-624) entering Phase I trials for solid tumors in Q2 2024.

• 3867-55-8(1,2,4-Benzenetricarbonyltrichloride)
• 21900-46-9(2,3-Dimethylbenzoyl chloride)
• 88-95-9(o-Phthaloyl dichloride)
• 117886-88-1(2-Formylbenzoyl Chloride)
• 21900-42-5(2,4-dimethylbenzoyl chloride)
• 42908-86-1(2-Chloromethyl-benzoyl Chloride)
• 933-88-0(o-Toluoyl chloride)
• 34824-32-3(Benzoyl chloride,2,4,5-trimethyl-)
• 22328-43-4(2,5-Dimethylbenzoyl Chloride)
• 21900-37-8(Benzoyl chloride,2,6-dimethyl-)