1,2-Dimethoxybenzene

Chemical properties

Colorless crystals or liquid. Soluble in alcohol and ether; slightly soluble in water.

Occurrence

Reported present in asparagus (raw and cooked), bonito (dried), broccoli (cooked), cauliflower (cooked), cognac, endive, grape, Gruyere de Comte cheese, guava, leek (raw and heated), olive, peas, rhubarb, rice bran and vanilla extract.

The Uses of 1,2-Dimethoxybenzene

1,2-Dimethoxybenzene (Veratrole) is helpful for organic synthesis of aromatic compounds. It is a a common reagent in organic synthesis, such as arizonins B1 and C1 synthesis. It is also used in the synthesis of pharmacophores of salmeterol and roflumilast as dual β2-adrenoreceptor agonists-PDE4 inhibitors. It was used to investigate the electroantennogram response of vine weevil Otiorhynchus sulcatus to plant volatiles.

Definition

ChEBI: A dimethoxybenzene with the methoxy groups at ortho-positions.

Preparation

Prepared by methylation of pyrocatechol.

Taste threshold values

Intolerable at 40 ppm.

General Description

1,2-Dimethoxybenzene reacts with Li{N(SO₂CF₃)₂} to yield molecular crystal [Li{N(SO₂CF₃)₂}{C₆H₄(OCH₃)₂}₂] having solid-state lithium ion conductivity. It is a potential pollinator attractant of the nocturnal moth Hadena bicruris.

Toxicology

Data from 1,2-dimethoxybenzene and read-across analog 1,4-dimethoxybenzene (CAS # 150-78-7) show that 1,2-dimethoxybenzene is not expected to be genotoxic. Data show that there are no safety concerns for 1,2-dimethoxybenzene for skin sensitization under the current declared levels of use. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class I material, and the exposure to 1,2-dimethoxybenzene is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; 1,2-dimethoxybenzene is not expected to be phototoxic/photoallergenic. For the environmental endpoints, 1,2-dimethoxybenzene is not a PBT as per the IFRA Environmental Standards, and its risk quotients (i.e., PEC/PNEC) for the aquatic environment, based on its current volume of use in Europe and North America, are < 1

Synthesis

According to the difference in raw material, the production method of 1,2-Dimethoxybenzene mainly contains the pyrocatechol method, guaiacol method and adjacent halobenzene methyl ether method. Methyl catechol is the monomethylation product of raw material with the pyrocatechol, and two methylates are 1,2-dimethoxy benzenes. In specific, it utilizes pyrocatechol, strong base and chloromethane as raw materials and water as solvent to react in a high-pressure autoclave, wherein the mol ratio of strong base to pyrocatechol is 2-3:1, the mole ratio of chloromethane to pyrocatechol is 2-3:1, the reaction temperature is 50-100 DEG C, the reaction pressure is 0.3-0.5 MPa, the reaction time is 4-10h, and the 1,2-Dimethoxybenzene is obtained through carrying out liquid separating and rectification on reaction liquid. The method of the invention is adopted to synthesize 1,2-Dimethoxybenzene.

Purification Methods

Steam distil veratrole, then fractionally distil it from BaO, CaH2 or Na. Crystallise it from *benzene or low-boiling pet ether at 0o. Fractionally crystallise it from its melt. Store it over anhydrous Na2SO4. [Beilstein 6 IV 5564.]