70918-53-5

Basic information

• Product Name: (R)-1,4-Benzodioxane-2-carboxylic acid
• Synonyms: (R)-2,3-DIHYDRO-1,4-BENZODIOXIN-2-CARBOXYLIC ACID;(R)-1,4-BENZODIOXANE-2-CARBOXYLIC ACID;(R)-1,4-BENZODIOXAN 2-CARBOXYLIC ACID;(R)-2,3-DIHYDRO-BENZO[1,4]DIOXINE-2-CARBOXYLIC ACID ;(R)-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylic acid;(R)-1,4-Benzodioxane-2-carboxylic acid >=97.0% (sum of enantiomers, GC);(3R)-2,3-Dihydro-1,4-benzodioxine-3-carboxylic acid
• CAS NO: 70918-53-5
• Molecular Formula: C₉H₈O₄
• Molecular Weight: 180.16
• Mol File: 70918-53-5.mol

Chemical Properties

• Melting Point: 96-99 °C
• Boiling Point: 347.2 °C at 760 mmHg
• Flash Point: 145.4 °C
• Appearance: /
• Density: 1.379 g/cm₃
• Vapor Pressure: 2.07E-05mmHg at 25°C
• Refractive Index: 1.574
• Storage Temp.: 2-8°C
• PKA: 2.69±0.20(Predicted)
• BRN: 5742837
• CAS DataBase Reference: (R)-1,4-Benzodioxane-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-1,4-Benzodioxane-2-carboxylic acid(70918-53-5)
• EPA Substance Registry System: (R)-1,4-Benzodioxane-2-carboxylic acid(70918-53-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 70918-53-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-1,4-Benzodioxane-2-carboxylic acid is used as a chiral synthon for the preparation of doxazosin mesylate, a drug that treats benign prostatic hyperplasia. Its role in the synthesis of this medication is crucial, as it contributes to the development of effective treatments for this common condition in men.
Used in Chemical Synthesis:
As a chiral synthon, (R)-1,4-Benzodioxane-2-carboxylic acid is also utilized in the synthesis of other organic compounds and molecules with potential applications in various industries, such as agriculture, materials science, and environmental science. Its versatility in chemical reactions allows for the creation of new compounds with specific properties and functions.

InChI:InChI=1/C9H8O4/c10-9(11)8-5-12-6-3-1-2-4-7(6)13-8/h1-4,8H,5H2,(H,10,11)/t8-/m1/s1

Upstream product

• 367-12-4 2-fluorophenol 
• 120-80-9 benzene-1,2-diol 
• 67471-01-6 1,4-benzodioxin-2-carboxylic acid 
• 533-58-4 2-Iodophenol 
• 98572-00-0 (S)-2-hydroxymethyl-1,4-benzodioxane 
• 62501-71-7 (S)-2-benzyloxymethyl-2,3-dihydrobenzodioxane 
• 3663-79-4 methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate 
• 650597-66-3 (R)-methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate 
• 3663-80-7 1,4-benzodioxane-2-carboxylic acid 
• 251104-20-8 (3R)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (2R)-2,3-dihydro-1,4-benzodioxine-2-carboxylate 
• 3663-82-9 2-hydroxymethyl-2,3-dihydrobenzo[1,4]dioxin 
• 1008-92-0 2-cyano-1,4-benzodioxane 
• 4739-94-0 ethyl 2,3-dihydro-1,4-benzodioxin-2-carboxylate 
• 623-73-4 diazoacetic acid ethyl ester 

Downstream Products

• 3663-79-4 methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate 
• 70918-54-6 (S)‐1,4‐benzodioxane‐2‐carboxylic acid 
• 1393911-85-7 C₂₁H₁₆N₂O₃S 
• 104874-86-4 (R)-doxazosin 
• 74191-85-8 doxazosin 
• 1219800-50-6 (R)-tert-butyl 4-(2,3-dihydrobenzo[b][1,4]dioxine-2-carbonyl)piperazine-1-carboxylate 
• 860173-98-4 (R)-N-(1,4-benzodioxan-2-carbonyl)piperazine 
• 446856-99-1 C₁₅H₁₂BrNO₃ 
• 1072906-06-9 N-(4-bromo-2-(2-(dimethylamino)ethoxy)phenyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxamide 
• 1052063-15-6 N-(2,2-diphenylethyl)-2,3-dihydro-1,4-benzodioxine-2-carboxamide 
• 84957-87-9 Bis-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-amine 
• 98572-00-0 (S)-2-hydroxymethyl-1,4-benzodioxane 
• 70918-00-2 (2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(piperazin-1-yl)methanone 
• 251104-26-4 (+)-N₂-[(1R,2R,3R)-2-hydroxy-3-phenoxycyclopentyl]-(2R)-2,3-dihydro-1,4-benzodioxine-2-carboxamide 

Relevant articles and documents

Highly efficient resolutions of 1,4-benzodioxane-2-carboxylic acid with para substituted 1-phenylethylamines

The salts of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid with eight (S)-1-arylethylamines were prepared. The determination of their melting points and of their solubilities in alcohol solvents revealed large differences between the diastereomeric benzodioxanecarboxylates of (S)-1-(p-nitrophenyl)ethylamine and of (S)-1-(p-methylphenyl)ethylamine. Therefore, these latter amines were selected to resolve (±)-1,4-benzodioxane-2-carboxylic acid by diastereoselective crystallization finding that both of them display a very high resolution ability for such a substrate, which contrasts with the null efficiency of unsubstituted 1-phenylethylamine. These results are consistent with DSC evidences, which indicated that the two successfully resolved diastereomeric systems are binary mixtures exhibiting a eutectic with a high content of the more soluble diastereomeric salt. The new procedures can advantageously replace the two resolutions we had previously reported, that of the same acid with dehydroabietylamine and that of glycerol acetonide, a precursor of 1,4-benzodioxane-2-carboxylic acid, with 1-phenylethylamine.

Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)

Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.

Preparation method of 1,4-benzdioxan-2-formic acid

The invention provides a preparation method of 1,4-benzdioxan-2-formic acid. The preparation method comprises the following steps: by taking benzylodiglycidyl ether and o-halogen phenol as raw materials, performing cyclization reaction, debenzylation reaction and oxidization reaction to obtain the 1,4-benzdioxan-2-formic acid. The preparation method provided by the invention is simple in reactionprocess; as the benzylodiglycidyl ether and the o-halogen phenol are used as the raw materials for reaction, no pollutants are produced, and no-irritative and no-allergic objects are produced; compared with other existing lines, the preparation method is environmentally friendly, high in total yield and favorable for mass production; the ee value of the finally prepared 1,4-benzdioxan-2-formic acid is more than or equal to 99 percent, and the chiral purity is high.

Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation

Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation methodology, as the key step with up to 10 000 TON, was successfully applied to develop highly efficient synthetic routes for the construction of some important biologically active molecules, such as MKC-242, WB4101, BSF-190555, and (R)-doxazosin·HCl.

Method for synthesizing doxazosin

The invention discloses a method for synthesizing doxazosin and belongs to the technical field of chemical synthesis. According to the method, the doxazosin is synthesized by adopting a synthesis route, represented by formulae shown in the description, different from the conventional technologies, and thus a novel synthesis route is provided for preparing the doxazosin; and the method has the advantages of moderate conditions, simple and convenient steps and high yield, and the doxazosin can be obtained simply and efficiently.

Crystallization-based resolution of 1,4-benzodioxane-2-carboxylic acid enantiomers via diastereomeric 1-phenylethylamides

Unlike the diastereomeric 1-phenylethylammonium salts, the diastereomeric N-1-phenylethylamides of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid show significant differences in fusibility and solubility so as to be efficiently resolved by precipitation of the less soluble diastereomer (>98% de), while chromatographic purification of the unprecipitated fraction affords the more soluble one (>99% de). Overall, 95% of the former and 80% of the latter are recovered. The hydrolysis of the two resolved amides provides the two acid enantiomers and the resolving amine in quantitative yield and with unchanged stereoisomeric purity.

Ultrasound-assisted synthesis and biological evaluation of 1,4-benzodioxane-2-carboxyl-amino acids and Peptides

A series of peptides containing 1,4-benzodioxane nucleus were attempted to synthesize by conventional as well as green techniques like microwave-assisted and sonication, using dicyclohexylcarbodiimide (DCC) as a coupling reagent and triethylamine as a bas

Synthesis and biological evaluation of a series of benzoxazole/ benzothiazole-containing 2,3-dihydrobenzo[b][1,4]dioxine derivatives as potential antidepressants

A series of benzoxazole/benzothiazole-2,3-dihydrobenzo[b][1,4]dioxine derivatives (5a-5d and 8a-8j) was synthesized. Compounds were evaluated for binding affinities at the 5-HT1A and 5-HT2A receptors. Antidepressant activities of the compounds were screened using the forced swimming test (FST) and the tail suspension test (TST). The results indicated that the compounds exhibited high affinities for the 5-HT1A and 5-HT2A receptors and showed a marked antidepressant-like activity. Compound 8g exhibited high affinities for the 5-HT1A (Ki = 17 nM) and 5-HT2A (Ki = 0.71 nM) receptors; it also produced a decrease of the immobility time and exhibited potent antidepressant-like effects in the FST and TST in mice.

A facile approach to chiral 1,4-benzodioxane toward the syntheses of doxazosin, prosympal, piperoxan, and dibozane

The process describes the concise synthesis of (R/S)-enantiomers of doxazosin, an antidepressant drug and α-adrenergic receptor antagonists like prosympal, piperoxan, and dibozane in practical yields from easily available (R)-2,3-O-cyclohexylidene-d-glyce

Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin

The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (±)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee ～99%, E = 535) at 258 mmol (50 g/L) substrate concentration.