650597-66-3

Usage

Uses

1. Used in Pharmaceutical Industry:
1,4-Benzodioxin-2-carboxylic acid, 2,3-dihydro-, methyl ester, (2S)is used as a reactant for the preparation of benzo-fused heterocycle sulfamide derivatives from chroman-2-carboxylic acid. These derivatives are synthesized through amination and condensation reactions and are utilized for the treatment of pain.
2. Used in Chemical Synthesis:
1,4-Benzodioxin-2-carboxylic acid, 2,3-dihydro-, methyl ester, (2S)can also be used as an intermediate in the synthesis of various other organic compounds, particularly those with benzo-fused heterocycles. Its unique structure and functional groups make it a valuable building block for creating novel molecules with potential applications in various fields, such as pharmaceuticals, agrochemicals, and materials science.

Upstream product

• 67-56-1 methanol 
• 3663-80-7 1,4-benzodioxane-2-carboxylic acid 
• 120-80-9 benzene-1,2-diol 
• 4442-59-5 (2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)amine 
• 1492478-58-6 C₁₀H₁₁NO₃ 
• 1616377-88-8 rac-2-N,N-dichloroaminomethyl-1,4-benzodioxane 
• 70918-54-6 (S)‐1,4‐benzodioxane‐2‐carboxylic acid 
• 46049-48-3 (R)-2-((amino)methyl)-1,4-benzodioxane 
• 1616377-82-2 (R)-2-N,N-dichloroaminomethyl-1,4-benzodioxane 
• 3663-79-4 methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate 
• 70918-53-5 (+)-(2R)-2,3-dihydro-1,4-benzodioxine-2-carboxylic acid 
• 1616377-89-9 C₁₀H₁₁NO₃ 
• 1616377-80-0 (S)-2-N,N-dichloroaminomethyl-1,4-benzodioxane 
• 46049-49-4 (S)-(2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanamine 

Relevant academic research and scientific papers

A versatile catalyst system for enantioselective synthesis of 2-substituted 1,4-benzodioxanes

We report the synthesis of enantiomerically enriched 1,4-benzodioxanes containing alkyl, aryl, heteroaryl, and/or carbonyl substituents at the 2-position. The starting 1,4-benzodioxines were readily synthesized via ring closing metathesis using an efficient nitro-Grela catalyst at ppm levels. Excellent enantioselectivities of up to 99:1 er were obtained by using the versatile catalyst system [Ir(cod)Cl]2/BIDIME-dimer in the asymmetric hydrogenation of 2-substituted 1,4-benzodioxines. Furthermore, DFT calculations reveal that the selectivity of the process is controlled by the protonation step; and coordinating groups on the substrate may alter the interaction with the catalyst, resulting in a change in the facial selectivity.

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.

From 2-aminomethyl-1,4-benzodioxane enantiomers to unichiral 2-cyano- and 2-carbonyl-substituted benzodioxanes via dichloroamine

2-Substituted 1,4-benzodioxanes, such as 2-cyano-, 2-methoxycarbonyl-, 2-aminocarbonyl-, and 2-formyl-1,4-benzodioxane, are key synthons that for the most part are never described as enantiomers or are inadequately characterized for enantiomeric purity. They were prepared by quantitative N,N-dichlorination of (R)- and (S)-2-aminomethyl-1,4-benzodioxane and successive functional group conversions in high yields without any racemization of the stereogenic benzodioxane C(2).

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.

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.

A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods

(R)-1,4-Benzodioxane-2-carboxilic acid (R)-1 was obtained by resolution of the racemic acid 1 with stoichiometric or nonstoichiometric (+)- dehydroabietylamine (+)-2 in high chemical yield and enantiomeric excess. (S)-1 was isolated from the mother liquors of the crystallisation of (R)-1·(+)-2 and its enantiomeric excess maximised by recrystallisation procedures involving a precipitation under kinetic control or, alternatively, by conversion into the methyl ester followed by a single crystallisation. The different mechanisms of the two S enrichments is well explained by the binary phase diagrams of the acid and of the ester, which show that the former is a racemic compound, whereas the latter a conglomerate. The DSC analyses were extended to 2-hydroxymethyl- and 2-mesyloxymethyl-1,4-benzodioxane, establishing that the alcohol forms a racemic compound, while its mesyl ester a conglomerate. On the basis of these results, different resolution strategies can be designed to obtain useful homochiral 2-substituted 1,4-benzodioxanes coupling the resolution of 1 via diastereomeric salt formation with the enantiomeric enrichments by recrystallisations, preferably of its conglomerate forming derivatives.

Synthesis and biological activity of novel carbacyclins having bicyclic substituents on the ω-chain

A number of carbacyclins having bicyclic substituents on the ω-chain have been synthesized and tested for antiplatelet aggregation activity in vitro (against collagen-induced aggregation of rat platelet), for reduction of systemic blood pressure in vivo (ability to reduce the blood pressure in anesthetized rat by iv injection), and for cytoprotective activity (protection against ethanol-induced rat gastric lesion). The most effective compound for each activity was [3aS-[2E,3aα,4α(3R),5β,6aα]]-5-[hexahydro-5-hydroxy-4-[3-hydroxy-3-(2- indanyl)-1-propynyl]-2(1H)-pentalenylidene]pentanoic acid (compound 11a), while some 1,4-benzodioxan analogues had selectivity for organ-protective activity, and indan analogues showed selectivity in their antiaggregation activity.