4065-45-6

Basic information

• Product Name: 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid
• Synonyms: Uvistat 1121;UV ABSORBER HMBS;TIMTEC-BB SBB002961;SULISOBENZONE;spectra-sorb uv 284;5-BENZOYL-4-HYDROXY-2-METHOXYBENZENESULFONIC ACID;2-HYDROXY-4-METHOXYBENZOPHENONE-5-SULPHONIC ACID;2-HYDROXY-4-METHOXYBENZOPHENONE-5-SULFONIC ACID
• CAS NO: 4065-45-6
• Molecular Formula: C₁₄H₁₂O₆S
• Molecular Weight: 308.31
• EINECS: 223-772-2
• Product Categories: Industrial/Fine Chemicals;Aromatic Benzophenones & Derivatives (substituted);Organic acids;Building Blocks;Chemical Synthesis;Organic Building Blocks;Sulfonic/Sulfinic Acids;Sulfur Compounds;SUNGARD
• Mol File: 4065-45-6.mol
• Article Data: 13

Chemical Properties

• Melting Point: 170 °C
• Boiling Point: 0°C
• Flash Point: 0°C
• Appearance: /
• Density: 1.4574 (rough estimate)
• Vapor Pressure: 0Pa at 25℃
• Refractive Index: 1.5300 (estimate)
• Storage Temp.: -20°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: -0.70±0.50(Predicted)
• Water Solubility: 300.92g/L at 25℃
• Merck: 14,8983
• BRN: 2889165
• CAS DataBase Reference: 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid(4065-45-6)
• EPA Substance Registry System: 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid(4065-45-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39-36/37/39-27
• WGK Germany: 1
• RTECS: DB5044300
• TSCA: Yes
• Hazardous Substances Data: 4065-45-6(Hazardous Substances Data)

Usage

Chemical Properties

white to yellowish powder

Originator

Uval,Dome,US,1965

Uses

Different sources of media describe the Uses of 4065-45-6 differently. You can refer to the following data:
1. Ultraviolet absorber for leather and textile fibers; in cosmetics and shampoos.
2. 2-Hydroxy-4-methoxybenzophenone-5-sulfonic acid is a commonly used, FDA approved sunscreen chemical with uVA-absorbing properties and an approved usage level of 5 to 10 percent. It protects a formulation from the effects of uV-light exposure.
3. sulisobenzone is the drug name for benzophenone-4, a sunscreen chemical.

Manufacturing Process

663 g of dichloroethane and 74.6 g 2-hydroxy-4-methoxybenzophenone were charged into a 3-neck flask equipped with stirrer, thermometer, reflux condenser and dropping funnel and a heating mantle. The solution was heated to the reflux temperature (85°C to 86°C) and was dehydrated by distilling off 66.5 g 1,2-dichloroethane. While maintaining at reflux, 30 g chlorosulfonic acid was added slowly over a period of about two hours. The rate of addition was regulated by the speed of evolution of the HCl. After all the chlorosulfonic acid was added, the charge was still maintained at reflux for an additional 15 minutes to remove traces of HCl. It was then cooled to 5°C and filtered. The filter cake was washed with 500 g cold 1,2-dichloroethane and dried. 98 g of product were obtained.

Brand name

Sungard (Bayer).

General Description

Sulisobenzone is a broad spectrum organic UV filter in sunscreen formulations, known to absorb deleterious UV light.

Flammability and Explosibility

Nonflammable

Contact allergens

BZP-4 is widely used in cosmetics, particularly shampoos and hair products. Cross-reactivity is rarely expected in patients photoallergic to ketoprofen.

InChI:InChI=1/C14H12O6S/c1-20-12-8-11(15)10(7-13(12)21(17,18)19)14(16)9-5-3-2-4-6-9/h2-8,15H,1H3,(H,17,18,19)/p-1

Synthetic route

Benzophenone-3 (131-57-7) → 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6)

Conditions	Yield
With sulfur trioxide; acetic acid In 1,2-dichloro-ethane at 25℃; for 3h; Inert atmosphere;	98.82%
With chlorosulfonic acid In ethyl acetate at 45℃; Temperature;	96%
With chlorosulfonic acid In phthalic acid dimethyl ester
With chlorosulfonic acid at 25℃; for 20h; Inert atmosphere; Autoclave;

4-benzoyloxy-2-methoxybenzenesulfonic acid → 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6)

Conditions	Yield
In methanol at 35℃; for 0.333333h; UVB irradiation;

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + chlorobenzene (108-90-7) → C14H11O6S(1-)*C18H12Cl3S(1+) (817203-48-8)

Conditions	Yield
Stage #1: chlorobenzene With thionyl chloride; aluminum (III) chloride at 20 - 150℃; for 5h; Stage #2: With water at 60℃; for 1h; Stage #3: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid In water for 4h;	79%

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → 3,5-dichloro-2-hydroxy-4-methoxybenzophenone (158547-83-2)

Conditions	Yield
With trichloroisocyanuric acid; sodium hydrogencarbonate In water	33%

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → 5-benzoyl-3-chloro-4-hydroxy-2-methoxybenzenesulfonic acid (1631050-95-7)

Conditions	Yield
With hydrogenchloride; sodium hypochlorite In water for 2h; Cooling with ice;	18%

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + diethyl dicarbonate (1609-47-8) → 2--4-methoxy-5-sulfo-benzophenon (19337-04-3)

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + dimethyl sulfate (77-78-1) → sodium 2,4-dimethoxy-5-benzoylbenzenesulfonate

Conditions	Yield
With sodium hydroxide Heating;

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonyl chloride (121715-18-2)

2-[2-[2-chloro-3-[(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-1,3,3-trimethyl-3H-indolium bromide + 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → 2-[2-[2-chloro-3-[(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-1,3,3-trimethyl-3H-indolium, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid salt

Conditions	Yield
Stage #1: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid With sodium hydrogencarbonate In 1-methoxy-2-propanol; water Stage #2: 2-[2-[2-chloro-3-[(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-1,3,3-trimethyl-3H-indolium bromide In 1-methoxy-2-propanol; water at 20℃; for 2.16667h; In the dark;

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + 3-nitro-aniline (99-09-2) → 1-[2-hydroxy-4-methoxy-5-(3-nitrophenylazo)phenyl]-1-phenylmethanone (1243203-31-7)

Conditions	Yield
Stage #1: 3-nitro-aniline With hydrogenchloride In water at 70℃; for 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; Stage #3: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid regioselective reaction; Further stages;	10.73 %Chromat.

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + 2-nitro-aniline (88-74-4) → 1-[2-hydroxy-4-methoxy-5-(2-nitrophenylazo)phenyl]-1-phenylmethanone (1243203-29-3)

Conditions	Yield
Stage #1: 2-nitro-aniline With hydrogenchloride In water at 70℃; for 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; Stage #3: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid regioselective reaction; Further stages;	5.14 %Chromat.

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + 2,4-Dinitroanilin (97-02-9) → C20H14N4O7 (1446786-84-0)

Conditions	Yield
Stage #1: 2,4-Dinitroanilin With sulfuric acid; sodium nitrite at 0 - 70℃; Stage #2: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid With sodium carbonate In ethanol at -20℃; for 2.5h; pH=8 - 9; Stage #3: With hydrogenchloride In ethanol; water pH=3; regioselective reaction;	9.9 %Chromat.

4-trifluoromethylphenylamine (455-14-1) + 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → C21H15F3N2O3 (1446786-85-1)

Conditions	Yield
Stage #1: 4-trifluoromethylphenylamine With hydrogenchloride; sodium nitrite In water at 0 - 5℃; Stage #2: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid With sodium carbonate In ethanol; water at -20℃; for 2.5h; pH=8 - 9; Stage #3: With hydrogenchloride In ethanol; water pH=3; regioselective reaction;	13.2 %Chromat.

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + 4-nitro-aniline (100-01-6) → 1-[2-hydroxy-4-methoxy-5-(4-nitrophenylazo)phenyl]-1-phenylmethanone (1243203-30-6)

Conditions	Yield
Stage #1: 4-nitro-aniline With hydrogenchloride In water at 70℃; for 0.5h; Stage #2: With sodium nitrite In water at 0 - 5℃; Stage #3: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid Temperature; Solvent; regioselective reaction; Further stages;	43.94 %Chromat.

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → C14H11O6S

Conditions	Yield
In water; acetonitrile Photolysis; Inert atmosphere;

2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) → Benzophenone-3 (131-57-7)

Conditions	Yield
With sulfuric acid; water at 110℃; for 5h; Temperature; Reagent/catalyst;	85.95 g

magnesium(II) nitrate hexahydrate + zinc(II) nitrate hexahydrate + aluminum nitrate hexahydrate + (E)-3-phenylacrylic acid (140-10-3) + 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + water (7732-18-5) + sodium hydroxide (1310-73-2) → Mg0.499Zn0.221Al0.280(OH)2(cinnamate)0.140(2-hydroxy-4-methoxybenzophenone-5-sulphonate)0.140*1.06H2O

Conditions	Yield
Stage #1: (E)-3-phenylacrylic acid; 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid; water; sodium hydroxide at 80℃; Inert atmosphere; Stage #2: magnesium(II) nitrate hexahydrate; zinc(II) nitrate hexahydrate; aluminum nitrate hexahydrate; water at 20℃; for 0.666667h; Inert atmosphere; Stage #3: (E)-3-phenylacrylic acid With sodium hydroxide at 95℃; for 12h; pH=Ca. 6.62; Inert atmosphere;

magnesium(II) nitrate hexahydrate + zinc(II) nitrate hexahydrate + aluminum nitrate hexahydrate + 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (4065-45-6) + water (7732-18-5) + sodium hydroxide (1310-73-2) → Mg0.465Zn0.245Al0.291(OH)2(2-hydroxy-4-methoxybenzophenone-5-sulphonate)0.291*1.28H2O

Conditions	Yield
Stage #1: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid; water; sodium hydroxide at 80℃; Inert atmosphere; Stage #2: magnesium(II) nitrate hexahydrate; zinc(II) nitrate hexahydrate; aluminum nitrate hexahydrate; water at 20℃; for 0.666667h; Inert atmosphere; Stage #3: With sodium hydroxide at 95℃; for 12h; pH=Ca. 6.62; Inert atmosphere;

Upstream product

• 131-57-7 Benzophenone-3 

Downstream Products

• 19337-04-3 2--4-methoxy-5-sulfo-benzophenon 
• 121715-18-2 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonyl chloride 
• 131-57-7 Benzophenone-3 
• 158547-83-2 3,5-dichloro-2-hydroxy-4-methoxybenzophenone 
• 1631050-95-7 5-benzoyl-3-chloro-4-hydroxy-2-methoxybenzenesulfonic acid 
• 1243203-30-6 1-[2-hydroxy-4-methoxy-5-(4-nitrophenylazo)phenyl]-1-phenylmethanone 
• 1446786-85-1 C₂₁H₁₅F₃N₂O₃ 
• 1446786-84-0 C₂₀H₁₄N₄O₇ 
• 1243203-29-3 1-[2-hydroxy-4-methoxy-5-(2-nitrophenylazo)phenyl]-1-phenylmethanone 
• 1243203-31-7 1-[2-hydroxy-4-methoxy-5-(3-nitrophenylazo)phenyl]-1-phenylmethanone 
• 817203-48-8 C₁₄H₁₁O₆S^(1-)*C₁₈H₁₂Cl₃S⁽¹⁺⁾ 

Relevant articles and documents

Preparation method of sun-screening agent 2-hydroxy-4-methoxy-5-sulfo benzophenone

The invention provides a preparation method of a sun-screening agent 2-hydroxy-4-methoxy-5-sulfo benzophenone. According to the method, SO3 is used as a sulfonating agent, the process conditions are mild, the reaction process is easy to control, the product selectivity is good, byproducts are few, and the purification process is simple and feasible. Compared with a traditional process, the production of waste acid is greatly reduced, the water content in the product is greatly reduced, acidic impurities are reduced to a great extent, the product quality is further improved, and the method is agreen and environment-friendly process and is beneficial to industrial production.

Synthesis process for 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid

The invention discloses a synthesis process for 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid. The process comprises the treatment flow: adding 2-hydroxy-4-methoxybenzophenone and a solvent into an enamel reaction kettle, dripping chlorosulfonic acid under the protection of nitrogen with stirring, controlling the temperature of the materials in the kettle to be 20-25 DEG C through jacket water bath cooling and control of the dripping speed of the chlorosulfonic acid, and performing a reaction for 20-25 h; performing centrifugal filtering separation on a product after reaction is finished, washing the product by using a corresponding solvent, and drying the product under the protection of the nitrogen; recycling a hydrogen chloride (HCl) byproduct in an HCl recycling packing tower in a water circulation mode to form a 20%-30% hydrochloric acid aqueous solution, and neutralizing a little hydrogen chloride gas of tail gas by using a solid alkali packing tower; and performing distillation recycling of the solvent by using an atmospheric distillation tower of a solvent distillation recycling system, and recycling 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid from raffinate at the bottom of the kettle.

A composition for lightening skin and hair

Suggested is a composition comprising (a) sclareolide and (b1) at least one tyrosinase inhibitor; and/or (b2) at least one sun protection factor; and/or (b3) at least one anti-oxidants; and/or (b4) at least one anti-inflammatory agent; and/or (b5) at least one desquamating agent.