707-07-3

Basic information

• Product Name: Trimethyl orthobenzoate
• Synonyms: (trimethoxymethyl)-benzen;(Trimethoxymethyl)benzene;Methyl orthobenzoate;Orthobenzoic acid, trimethyl ester;Thrimethyl orthobenzoate;Benzene, (trimethoxymethyl)-;à,à,à-trimethoxytoluene;Phenylorthoformic acid trimethyl ester
• CAS NO: 707-07-3
• Molecular Formula: C₁₀H₁₄O₃
• Molecular Weight: 182.22
• EINECS: 211-897-5
• Product Categories: Acetals/Ketals/Ortho Esters;Organic Building Blocks;Oxygen Compounds
• Mol File: 707-07-3.mol

Chemical Properties

• Boiling Point: 87-88 °C7 mm Hg(lit.)
• Flash Point: 180 °F
• Appearance: Clear colorless/Liquid
• Density: 1.061 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.344mmHg at 25°C
• Refractive Index: n20/D 1.489(lit.)
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Soluble in organic solvents.
• Sensitive: Moisture Sensitive
• Stability: Hygroscopic
• BRN: 777623
• CAS DataBase Reference: Trimethyl orthobenzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Trimethyl orthobenzoate(707-07-3)
• EPA Substance Registry System: Trimethyl orthobenzoate(707-07-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39-37/39
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 707-07-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Trimethyl orthobenzoate is used as a reagent for the synthesis of quinazolines, which are a class of compounds with potential applications in the development of new drugs.
Used in the Treatment of Idiopathic Pulmonary Fibrosis:
Trimethyl orthobenzoate is used in the preparation of nintedanib (N478290), a drug used in the treatment of idiopathic pulmonary fibrosis. This condition is a chronic and progressive lung disease characterized by the scarring of lung tissue, leading to impaired lung function.
Used in Cancer Therapy:
Trimethyl orthobenzoate inhibits the process of blood vessel formation, which is essential for the growth and spread of cancer cells. By inhibiting this process, it may assist in cancer therapy by limiting the ability of tumors to receive necessary nutrients and oxygen, thereby slowing their growth and progression.

Synthesis Reference(s)

Journal of the American Chemical Society, 72, p. 1661, 1950 DOI: 10.1021/ja01160a067

InChI:InChI=1/C10H20O3/c1-11-10(12-2,13-3)9-7-5-4-6-8-9/h9H,4-8H2,1-3H3

Upstream product

• 1850-14-2 tetramethoxymethane 
• 124-41-4 sodium methylate 
• 98-07-7 Benzotrichlorid 
• 67-56-1 methanol 
• 637-50-3 1-phenylpropene 
• 1125-88-8 benzaldehyde dimethyl acetal 
• 59484-16-1 phenyl N-phenylbenzimidate 
• 611-73-4 Benzoylformic acid 
• 1934-92-5 N-methyl-N-phenyl-benzamide 
• 333-27-7 methyl trifluoromethanesulfonate 
• 5873-90-5 methyl benzimidate hydrochloride 
• 100-47-0 benzonitrile 
• 7471-86-5 methyl benzimidate 
• 108-88-3 toluene 

Downstream Products

• 74091-54-6 3-Phenyl-2,4,10-trioxa-adamantane 
• 54075-76-2 trimethyloxonium hexachloroantimonate^(1-) 
• 15224-25-6 3-benzoylindole 
• 26211-73-4 (2-methyl-1H-indol-3-yl)phenylmethanone 
• 104699-67-4 2-(5-Amino-1,2,3-triazol-4-yl)-5-phenyl-1,3,4-oxadiazole 
• 1022-45-3 2-phenyl-4(3H)-quinazolinone 
• 72320-30-0 2-phenyl-2-methoxy-5,5-dimethyl-1,3-dioxane 
• 1904-60-5 3-amino-2-phenylquinazolin-4(3H)-one 
• 30909-95-6 3,4-Dihydro-2-phenyl-5H-1,3,4-benzotriazepin-5-one 
• 23047-95-2 2-(o-aminophenyl)-5-phenyl-1,3,4-oxadiazole 
• 56883-02-4 2',3'-O-(α-methoxybenzylidene)adenosine 
• 93-58-3 benzoic acid methyl ester 
• 37856-14-7 2-phenyl-3-(4-tolyl)quinazolin-4(3H)-one 
• 22686-82-4 2,3-diphenyl-3H-quinazolin-4-one 

Relevant articles and documents

Anodic oxidation of dithiane carboxylic acids: A rapid and mild way to access functionalized orthoesters

A new electrochemical methodology has been developed for the preparation of a wide variety of functionalized orthoesters under mild and green conditions from easily accessible dithiane derivatives. The new methodology also offers an unprecedented way to access tri(fluorinated) orthoesters, a class of compound that has never been studied before. This provides the community with a rapid and general method to prepare libraries of functionalized orthoesters from simple and readily available starting materials.

Enantioselective Desymmetrization of cis-3,5- O-Arylidenecyclohexanones Catalyzed by Cinchona-Derived Quaternary Ammonium Salts

An enantioselective protocol for the desymmetrization of cis-3,5-O-arylidenecyclohexanones has been developed that proceeded under the catalysis of readily available and inexpensive Cinchona-derived quaternary ammonium salts. The synthetic relevance of the methodology was exemplified by the synthesis of a key intermediate that could be used in the preparation of the active pharmaceutical ingredient, paricalcitol (Zemplar).

A flexible Pinner preparation of orthoesters: The model case of trimethylorthobenzoate

In the absence of additional solvents, a novel procedure was implemented for the synthesis of trimethylorthoesters through the Pinner reaction. At 5 °C, the reaction of both aliphatic and aromatic nitriles (RCN; R = Et, Bu, Ph) with a moderate excess of MeOH and gaseous HCl gave the corresponding imidate hydrochlorides [RC(NH)OR′·HCl] in excellent yields (>90%). At 25-65 °C, the methanolysis of alkyl imidate salts provided trimethylortho-propionate and valerate, while only traces of trimethylorthobenzoate (TMOB) were observed. However, the aromatic hydrochloride could be readily converted into the hydrogenphosphate salt [PhC(NH) OR′·H3PO4] which, in turn, underwent a selective (>80%) reaction with MeOH to produce TMOB in a 62% isolated yield. This allowed for an unprecedented Pinner-type synthesis of TMOB starting from benzonitrile, rather than from the highly toxic trichloromethylbenzene. Overall, remarkable improvements in safety and process intensification were achieved.

ELECTROCHEMICAL CLEAVAGE OF THE DOUBLE BOND OF 1-ALKENYLARENES

A study has been made of the electrochemical cleavage of the double bond of propenylbenzene (Ia) and p-propenylanisole (Ib), which takes place upon anodic oxidation of (Ia, b) in alcoholic solutions of sodium trifluoroacetate and other electrolytes and which leads to conversion of (Ia, b) to benzaldehyde dialkylacetals.Conditions are found that provide for highly selective (>80percent) conversion of (Ib) and p-propenyltoluene to p-methyl- and p-methoxybenzaldehyde dimethylacetals.

Metastable Ion Study of Organosilicon Compounds. Part III - Trimethoxyphenylsilane

The unimolecular decomposition of trimethoxyphenylsilane (1) was investigated by mass-analysed ion kinetic energy (MIKE) spectrometry, deuterium-labelling studies and from high resolution data.The characteristic fragmentations of metastable molecular ion of 1 were losses of C6H6* and C7H7* with rearrangements.Almost complete H/D scrambling occurred in the molecular ion prior to these decompositions.The other important fragmentation routes corresponded to expulsion of CH3O* and C6H5*.These fragmentations were followed by consecutive elimination of an H2CO molecule, as commonly observed in the mass spectra of alkoxysilanes.In these fragmentation processes, H/D scrambling increased as the internal energy of the molecular ion was lowered.The fragmentations of 1 were compared with those of its carbon analogue, α,α,α-trimethoxytoluene.

Influence of Solvent and Counterion in the Reactions of Alkoxide Ions with the 2-Nitropropan-2-yl Radical

Photostimulated free radical chain reactions between alkoxide ions derived from primary alcohols and XCMe2NO2 (X= Cl, Br, NO2, PhSO2, N3, or p-ClC6H4S) occur to produce Me2C(OR)2 by reaction involving the trapping of Me2C(NO2). by RO-, the decomposition of ROCMe2NO2.- to ROCMe2., and the oxidation of ROCMe2. to Me2C=OR+ by XCMe2NO2.

KINETICS AND MECHANISM OF SOLVOLYSIS OF SUBSTITUTED PHENYL N-PHENYLBENZIMIDOESTERS

Kinetics of hydrochloric acid-catalyzed solvolysis of substituted phenyl and methyl N-phenylbenzimidoesters have been studied in methanol, 50 vol. percent aqueous methanol, and 50 vol. percent aqueous tetrahydrofurane, and the composition of the reaction products has been determined.The rate-limiting step consists in addition of water or methanol to the protonated substrate.The reaction of methyl N-phenylbenzimidoester with both water and methanol and that of substituted phenyl N-phenylbenzimidoesters with methanol produce aniline, the ester (or orthoester) and the corresponding phenol.The reaction of substituted phenyl N-phenylbenzimidoesters with water gives both the neutral tetraheral intermediate (which is decomposed into phenol and anilide) and the protonated intermediate (which produces aniline and the ester).At the same proton concentration the phenol content increases with increasing value of the ? constant of the substituent.

INDIRECT ELECTROCHEMICAL SIDE-CHAIN OXIDATION OF ALKYL AROMATIC COMPOUNDS - SELECTIVE SYNTHESIS OF METHYL BENZOATES OR ORTHOBENZOIC ACID TRIMETHYLESTERS

The technically important side-chain oxidation of alkyl aromatic compounds to form either methyl benzoates or orthobenzoic acid trimethylesters can be performed electrochemically at low potentials in methanol solution using an undivided cell and tris(2,4-dibromophenyl)amine as redox catalyst.Under neutral or slightly acidic conditions methyl benzoates are selectively formed while under basic conditions the orthoesters are predominating.In a similar way ortho benzoic acid trimethylesters are formed selectively starting from benzaldehyde dimethylacetals.The redox catalyst is stable under the reaction conditions so that several thousand cycles can be performed without noticeable loss.