88-46-0

Usage

Uses

Used in Chemical Synthesis:
2,5-Dihydroxybenzenesulphonic acid is used as a chemical intermediate for the synthesis of various organic compounds and dyes. Its reactivity and solubility make it a versatile building block in the chemical industry.
Used in Pharmaceuticals:
In the pharmaceutical industry, 2,5-dihydroxybenzenesulphonic acid is used as a precursor for the development of drugs, particularly antibiotics such as sulfonamides. Its unique chemical structure allows for the creation of effective medications to combat bacterial infections.
Used in Dye Manufacturing:
2,5-Dihydroxybenzenesulphonic acid is utilized as a key component in the production of dyes for various applications, including textiles, plastics, and printing inks. Its ability to form colored compounds makes it an essential ingredient in the dye manufacturing process.
Used in Analytical Chemistry:
In analytical chemistry, 2,5-dihydroxybenzenesulphonic acid serves as a reagent for the detection and analysis of specific compounds. Its acidic properties and solubility make it suitable for use in various analytical techniques, such as titration and spectrophotometry.

Originator

Dicynone,Delalande,France,1965

Manufacturing Process

163 grams of pure diethylamine bisulfite are added to an ethyl alcohol solution of 108 grams of 1,4-benzoquinone at a temperature not above 5°C and under continuous stirring. After reaction, the alcohol is removed by distilling under vacuum. The product is recrystallized from ethyl alcohol at 80°C. Yield: 198 grams of diethylammonium cyclohexadienol 4-one-1- sulfonate-4. MP 125°C.

InChI:InChI=1/C6H6O5S/c7-4-1-2-5(8)6(3-4)12(9,10)11/h1-3,7-8H,(H,9,10,11)

Synthetic route

2,5-bis(acetyloxy)benzenesulfonic acid → dobesilate (88-46-0)

Conditions	Yield
With water; sodium hydroxide at 40℃; for 2h; Temperature;	91.1%

p-benzoquinone (106-51-4) → dobesilate (88-46-0) + hydroquinone (123-31-9)

Conditions	Yield
With sulfur dioxide In not given 0-80°C;	A 20% B 80%
With SO2 In not given 0-80°C;	A 20% B 80%
With sulphurous acid

p-benzoquinone (106-51-4) + sodium sulfite (7757-83-7) → dobesilate (88-46-0) + hydroquinone (123-31-9) + dithionic acid (14970-71-9)

Conditions	Yield
byproducts: H2SO4; slight amount of Na2S2O6;	A 57% B 3% C n/a
byproducts: H2SO4; slight amount of Na2S2O6;	A 57% B 3% C n/a

p-benzoquinone (106-51-4) + sodium sulfite (7757-83-7) → dobesilate (88-46-0)

Conditions	Yield
addn. of alkali;	35%
addn. of alkali;	35%

2,5-dichlorobenzenesulfonic acid (88-42-6) → dobesilate (88-46-0)

Conditions	Yield
With sodium hydroxide at 200℃; in einem Kupferkessel;

hydroquinone (123-31-9) → dobesilate (88-46-0)

Conditions	Yield
With sulfuric acid at 50 - 100℃; Kinetik;
With oxygen; sodium sulfite
Darst. durch Sulfurieren;

p-benzoquinone (106-51-4) → 2,5-dihydroxybenzene-1,4-disulphonic acid (4444-23-9) + dobesilate (88-46-0)

Conditions	Yield
With sodium sulfite

p-benzoquinone (106-51-4) → dobesilate (88-46-0)

Conditions	Yield
With sodium sulfite

hydroquinone (123-31-9) → 1,4-bis-sulfooxy-benzene (2458-55-1) + sulfuric acid mono-(4-hydroxy-phenyl ester) (17438-29-8) + dobesilate (88-46-0)

Conditions	Yield
With sulfur trioxide In nitromethane-d3 at 20℃; Product distribution; (with 1 equiv. SO3); product distribution between 10 and 10000 min;

hydroquinone (123-31-9) → sulfuric acid mono-(4-hydroxy-phenyl ester) (17438-29-8) + 2,5-dihydroxybenzene-1,4-disulphonic acid (4444-23-9) + dobesilate (88-46-0) + 2,5-dihydroxy-benzene-1,3-disulfonic acid (81010-88-0) + 2-Hydroxy-5-sulfooxy-benzene-1,3-disulfonic acid + 2-Hydroxy-5-sulfooxy-benzenesulfonic acid

Conditions	Yield
With sulfuric acid In water at 25℃; for 18.8889h; Product distribution; Rate constant; various times, concentrations;

sulfur trioxide (7446-11-9) + hydroquinone (123-31-9) → dobesilate (88-46-0)

Conditions	Yield
unter einer Glasglocke;

p-benzoquinone (106-51-4) + Na2SO3 → dobesilate (88-46-0)

p-benzoquinone (106-51-4) + Na2SO3 → dobesilate (88-46-0) + β-hydroquinonedisulfonic acid

water (7732-18-5) + p-benzoquinone (106-51-4) + SO2 → dobesilate (88-46-0) + hydroquinone (123-31-9)

benzene-1,4-diyl diacetate (1205-91-0) → dobesilate (88-46-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: chlorosulfonic acid / 1,2-dichloro-ethane / 2.5 h / 5 - 90 °C 2: sodium hydroxide; water / 2 h / 40 °C View Scheme

dabigatran etexilate (211915-06-9) + dobesilate (88-46-0) → dabigatran etexilate 2,5-dihydroxybenzenesulfonate

Conditions	Yield
In ethyl acetate at 30℃; Solvent; Temperature;	92%

Upstream product

• 88-42-6 2,5-dichlorobenzenesulfonic acid 
• 123-31-9 hydroquinone 
• 106-51-4 p-benzoquinone 
• 7446-11-9 sulfur trioxide 
• 7732-18-5 water 
• 7757-83-7 sodium sulfite 
• 1205-91-0 benzene-1,4-diyl diacetate 

Downstream Products

• 877-19-0 3,6-dioxo-cyclohexa-1,4-dienesulfonic acid 
• 23149-36-2 2,3,5-tribromo-1,4-dihydroxybenzene 
• 118-75-2 chloranil 
• 4444-23-9 2,5-dihydroxybenzene-1,4-disulphonic acid 
• 81010-88-0 2,5-dihydroxy-benzene-1,3-disulfonic acid 
• 123-31-9 hydroquinone 
• 20123-80-2 calcium dobesilate 
• 2624-44-4 ethamsylate 

Relevant academic research and scientific papers

Etamsylate and calcium dobesilate impurities, and preparation method and application thereof

The invention discloses four types of etamsylate and calcium dobesilate impurities, namely a 2,5-dihydroxy-1,4-benzene disulfonic acid compound, a 2,4-dihydroxy-1,5-benzene disulfonic acid compound, a2,5-dihydroxy benzene sulfonate compound and a 2,3-dihydroxy benzene sulfonic acid compound, and a preparation method thereof. The purity of all the prepared compound is 96% or more, and the compounds can be used for the quality control of etamsylate and calcium dobesilate bulk drugs and preparations.

Cornforth and Corey-Suggs reagents as efficient catalysts for sulfonation of aromatic and heteroaromatic compounds using NaHSO3 under solvent free and microwave conditions

Cornforth and Corey-Suggs reagents Pyridinium Dichromate (PDC) and Pyridinium Chlorochromate (PCC) were explored as efficient catalysts for sulfonation of aromatic and heteroaromatic compounds using NaHSO3 in aqueous acetonitrile medium at room temperature within 1–4 h, while microwave assisted reactions took place within 1–4 min under solvent-free conditions. These observations indicate significant rate accelerations in microwave assisted reactions. which were explained due to the bulk activation of molecules induced by insitu generated high temperatures and pressures when microwaves are transmitted through reaction medium.

C10H17NO5S.1/20H2O compound

The invention discloses a C10H17NO5S.1/20H2O compound and a preparation method thereof. The compound is measured by using a powder X-ray diffraction measurement method, and shows characteristic diffraction peaks represented by a diffraction angle of 2theta +/- 0.2 degrees at the places of 13.4 degrees, 17.2 degrees, 20.5 degrees, 21.4 degrees, 23.7 degrees, 24.5 degrees, 26.9 degrees, 28.0 degreesand 34.0 degrees. The C10H17NO5S.1/20H2O compound prepared by the preparation method has the advantages of good thermal stability, high purity, and weak hygroscopicity, has a simple process, a high yield and strong repeatability, and is suitable for industrial production.

Method for producing high-purity etamsylate

The invention discloses a method for producing high-purity etamsylate. The method comprises the following steps: carrying out a sulfonation reaction on hydroquinone serving as an initial material, a sulfonating agent, a dispersing agent and an organic solvent to obtain 2,5-dihydroxybenzenesulfonic acid; cooling the reaction solution to 45-70 DEG C, adding a mixed solution of diethylamine and waterto form a salt, cooling and crystallizing, so as to obtain the etamsylate. According to the reaction system used in the method, the fluidity of the system is improved, and the three-transfer-one-reaction efficiency is improved, so that the conversion rate of the materials is improved by 5-10%; when the system is cooled to 45-70 DEG C after the reaction is ended, the mixed solution of diethylamineand water is directly added into the system, the operation is simplified, and the after-treatment time is shortened; concentrated water is avoided, the energy consumption is reduced, and the yield ofthe product after salt formation reaches 80-85%; the product does not need to be re-crystallized or subjected to activated carbon discoloration, the purity directly reaches 99.5% or higher, and the content of all single impurities is lower than 0.05%; in addition, the use of a type of solvents and reagents containing genotoxicity warning structures is avoided, and totally safe and low-toxicity class-2 and class-3 solvents friendly to the humans and environment are used.

Hydroxybenzene disulphonic acid as well as calcium salt and preparation method thereof

A preparation method of hydroxybenzene disulphonic acid comprises steps as follows: hydroquinone and water-containing sulphuric acid are subjected to a reaction to produce a liquid containing hydroxybenzene sulphonic acid, the liquid containing hydroxybenzene sulphonic acid is subjected to a reaction with fuming sulphuric acid, and hydroxybenzene disulphonic acid is produced. A preparation methodof calcium hydroxybenzene disulphonate comprises steps as follows: a liquid containing hydroxybenzene sulphonic acid is produced from hydroquinone and sulphuric acid and is subjected to a reaction with fuming sulphuric acid, a liquid containing hydroxybenzene disulphonic acid is produced and subjected to a reaction with calcium carbonate, and calcium hydroxybenzene disulphonate is produced. The preparation method of hydroxybenzene disulphonic acid, calcium hydroxybenzene disulphonate and the preparation method of calcium hydroxybenzene disulphonate have the advantage that large-scale synthesisof hydroxybenzene disulphonic acid and calcium hydroxybenzene disulphonate is expected to be realized with a certain technology.

A 2, 5 - dihydroxy benzene sulfonic acid clopidogrel and its preparation method (by machine translation)

The invention discloses a 2, 5 - dihydroxy benzene sulfonic acid clopidogrel, its structural general formula is: 2. 5 - dihydroxy benzene sulfonic acid of clopidogrel process includes the steps of: (1) to hydroxyl-phenol with the role of the concentrated sulfuric acid, to chloroform as reaction solvent, refluxing the reaction condition, generating a 2, 5 - dihydroxy benzene sulfonic; (2) the clopidogrel hydrogen sulfate salt in alkaline conditions of clopidogrel free obtained; (3) using ethyl acetate as reaction solvent, under normal temperature conditions 2, 5 - dihydroxy benzene sulfonic acid with the clopidogrel reaction production 2, 5 - dihydroxy benzene sulfonic acid clopidogrel. Compounds of the invention have strong inhibiting thrombus and platelet aggregation effects and bad reaction of small advantages. (by machine translation)

Aminopeptidase N inhibition could be involved in the anti-angiogenic effect of dobesilates

Calcium, magnesium and zinc 2,5-dihydroxybenzenesulfonates (dobesilates) were synthesized by sulfonation of hydroquinone with sulfuric acid under mild conditions. To form the salts, neutralization with calcium carbonate followed by cation exchange by means of magnesium or zinc sulfates was performed. The dobesilates were characterized by standard spectral methods and by AAS for metal content and then tested for inhibitory activity against aminopeptidase N. Calcium and magnesium 2,5-dihydroxybenzene sulfonates exhibited rather weak inhibitory activity to aminopeptidase N as demonstrated by IC50 values of 978.0 and 832.1 umol l-1 respectively while zinc 2,5-dihydroxybenzene sulfonate reached the more significant inhibitory activity characterized by IC50 77.4 umol l-1. The inhibitory activity results suggest that the inhibition of aminopeptidase N could play a role in the anti-angiogenic activity of 2,5-dihydroxybenzenesulfonates.

Polymer electrolyte and process for producing the same

A polymer electrolyte having, in a main chain, a structural unit represented by the following formula (1):-[Ar1-(SO2-N-(X+)-SO2-Ar2)m-SO2-N-(X+)-SO2-Ar1-O]- wherein Ar1 and Ar2 independently represent a divalent aromatic groups, m represents an integer of 0 to 3, and X+ represents an ion selected from hydrogen ion, an alkali metal ion and ammonium ion, which is excellent in proton conductivity, thermal resistance and strength. The polymer electrolyte is soluble in solvents and has excellent film forming property and recycling efficiency.

Reactions of the dihydroxybenzenes and their methyl ethers with sulfur trioxide. The effect of initial sulfation on the sulfonation product distribution

The sulfation and sulfonation resulting from the reaction of the dihydroxybenzenes and their mono- and dimethyl ethers with SO3 in nitromethane have been studied, and their product distributions are reported.As to the non-hydroxy-substituent-containing substrates, 1,2-dimethoxybenzene (3) yields the 4-sulfonic acid (3-4-S) which, upon further sulfonation, yields a 1:4 mixture of the 3,5- and 4,5-S2.The 1,3- (6) and 1,4-isomer (9) yield initially the 4- and 2-S, respectively, and subsequently exclusively 6-4,6- and 9-2,5-S2, respectively.With the substrates containing one hydroxy substituent, the sulfonation isomer distribution is dependent on the SO3 to substrate ratio if the OH and OMe substituents are in ortho or para orientation, due to increasing sulfonation of the corresponding methoxyphenyl hydrogen sulfate.Thus, 2-methoxy- (2) and 4-methoxyphenol (8) with one equiv of SO3 at 0 deg C yield a 3:1 mixture of 2-4-S and 2-5-S and a 9:1 mixture of 8-2-S and 8-3-S, respectively, but, with >/= 4 equiv of SO3, the former reactant yields only 2-5-S and the latter only 8-3-S. 3-Methoxyphenol (5) yields initially a 1:1 mixture of the 4- and 6-sulfonic acid.Further sulfonation yields only 5-O,4,6-S3 which slowly cyclizes to the 1,3,2,4-benzodioxadithiin 2,2,4,4-tetraoxide derivative 11.As to the dihydroxy-containing substrates, 1,2-dihydroxybenzene (1) with 1 equiv of SO3 first yields the hydrogen sulfate 1-O-S which rearranges to 1-4-S; on using an excess of SO3, the eventual product is 1-O(2),4-S2.Similarly, the 1,4-isomer (7) with 1 equiv of SO3 yields initially 7-O-S which isomerizes to 7-2-S.With 6 equiv of SO3, initially 7-O,O-S2 is formed and subsequently its 2-sulfonic acid, which eventually cyclizes slowly to the 1,3,2,4-benzodioxadithiin 2,2,4,4-tetraoxide derivative 12.The 1,3-isomer 4 with 1 equiv of SO3 yields the 4-sulfonic acid.With 4 equiv of SO3, initially 4-O,O-S2 is formed and subsequently 4-4,O,O-S3, which is converted into both 4-O,O,4,6-S4 and the cyclization product 10.Eventually, small amounts of 4-O,2,4,6-S4 and 14-2,6-S2 are formed by transsulfonation.

Sulfonation and sulfation on reaction of 1,4-dihydroxybenzene and its methyl ethers in concentrated sulfuric acid

The homogeneous reactions of 1,4-dihydroxybenzene (1), its monomethyl (2) and dimethyl ether (3) and 2-3-sulfonic acid in 68-105percent H2SO4 at 25 deg C have been studied and isomer distributions and rate coefficients for the various subsequent sulfonations, as well as the equilibrium data for the sulfation (-OH -OSO3H), are reported.For 2, the ratio of 2- to 3-sulfonation decreases upon increasing the sulfuric acid concentration from 68-98.5percent H2SO4, due to a gradual change-over in the effective sulfonating entity from H3SO4(1+) to H2S2O7.For 1-2-sulfonic acid (1-2-S), 2-2-S and 2-3-S, the ratios of 5- to 6-sulfonation are all ca. 25:75, whereas 3-2-S only yields the 5-sulfonic acid.Demethylation of the sulfonic acids of 2 and 3 in = 98.5percent H2SO4 is of minor importance, but plays a major role in 105,0 percent H2SO4, the eventual products being the bis(hydrogen sulfate)s 10 and 15, the tricyclic bis(sulfate sulfonate anhydride) 11 and the bicyclic hydrogen sulfate 16.Mechanisms for the sulfodemethylation and for the cyclization of the 2-sulfophenyl hydrogen sulfate moiety to the 1,3,2,4-benzodioxadithiin 2,2,4,4-tetraoxide system are proposed.