99-76-3

Hazards Identification

GHS Hazard Statements:

H402: Harmful to aquatic life [Hazardous to the aquatic environment, acute hazard]
H412: Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes:

P273, and P501

Hazards Summary:

Parabens are an uncommon cause of allergic contact dermatitis; [Marks, p. 115] Food use limited to 0.1%; [Hawley] Observations from animal studies include mild skin and eye irritation and a low order of toxicity in high-dose oral studies; Skin sensitization has been reported from cosmetics and topical medications; A moderate eye irritant (saturated aqueous solution); Practically non-toxic in animal studies: Oral LD50 (mouse) >8000 mg/kg (Effects included flaccid paralysis and ataxia.); [HSDB] An eye and mild skin irritant; May cause skin sensitization; [eChemPortal: ERMA] Parabens can induce allergic contact dermatitis, mainly in chronic dermatitis and wounded skin. [Kanerva, p. 1822-3] An irritant; [MSDSonline]

Usage

Uses

Used in Cosmetic Industry:
Methylparaben is used as a preservative in beauty products such as cream cleansers, moisturizers, primers, and foundations. It provides anti-fungal and antibacterial properties, which help maintain the effectiveness and extend the shelf life of skincare, haircare, and cosmetic products.
Used in Pharmaceutical Industry:
Methylparaben is used as a preservative in pharmaceutical products, including ophthalmic solutions. It acts as an inhibitor of mold growth and to a lesser extent, bacterial growth, ensuring the safety and efficacy of these products.
Used in Food Industry:
Methylparaben is used as a preservative in foods and beverages. It is effective against yeast, molds, and bacteria, helping to maintain the quality and safety of these products over a wide pH range.
Used in Antimicrobial Applications:
Methylparaben is an antimicrobial agent that is active against yeast and molds. It is used in various applications where microbial control is necessary, such as in the production of cloudberry, yellow passion fruit juice, white wine, botrytised wine, and Bourbon vanilla.
General Description:
Methylparaben is a white free-flowing powder that is readily absorbed through the skin and gastrointestinal tract. Upon hydrolysis, it is hydrolyzed to p-hydroxybenzoic acid, and the conjugates formed get rapidly excreted in the urine.
Chemical Properties:
Methylparaben is a colorless crystalline powder that is odorless or has a faint characteristic odor and a slight burning taste. It is slightly soluble in water, easily soluble in ethanol, ether, acetone, and other organic solvents. Its effectiveness as a preservative increases with decreasing pH.
Aroma Threshold Values:
Detection: 2.6 ppm.

Content analysis

Method one: determinate according to the content analysis method in "butyl p-hydroxybenzoate (07002)". Per mL 1 mol/L sodium hydroxide is equivalent to the product (C8H8O3) 152.2mg. Method two: Take 0.1 g (accurate to 1 mg) of the sample previously dried on silica gel for 5 h and move into a 300 ml flask with a glass plug. Plus l mol/L sodium hydroxide 10ml, heated in the water bath for 15min. After cooling, add 0.1mol/L potassium bromate 0.00ml, potassium bromide 5.0g and l mol/L hydrochloric acid 30ml. Put 15min in the dark room after sealing. Add potassium iodide 1 g, shake the flask vigorously, with 0.1mol/L sodium thiosulfate titration, with starch test solution (TS-235) as an indicator. Per ml 0.1mol/L potassium bromate is equivalent to the product (C8H8O3) 25.36mg.

Toxicity

ADI 0～10mg/kg(FAO/WHO,2001). GRAS(FDA,§184．1490，2000). LD503000mg/kg(Dog, mouth)

Utilization limitation

FAO/WHO (1984): Jam, jelly, 1000mg/kg (single or with benzoate, sorbic acid and potassium sorbate). EEC(1990,mg/kg): For use in pigment solutions, flavor syrups, coffee extracts, frozen drinks, fruit, glucose and soft drinks, pickled fish, salad, sauce, snack food, concentrated soup and so on, limited to GMP; Beer 70; Snack cereals and soup concentrate 175, the same as "07018 p-hydroxybenzoate". HACSG is listed as a restricted list. FDA,§184.1490(2000):0.1%.

Preparation

The drug is esterified with p-hydroxybenzoic acid and methanol. The p-hydroxybenzoic acid was added to excess methanol to dissolve, stirring and adding concentrated sulfuric acid slowly. After heating and refluxing 10h, pour into the water to precipitate crystallization, then washed with water, sodium carbonate solution and water, finally obtain the crude product. Recrystallize from water or 25% ethanol to obtain finished product. The yield was 85%. Raw material consumption (kg/t): p-hydroxybenzoic acid 1200, methanol 1000.

Preparation

Produced by the methanol esterification of p-hydroxybenzoic acid in the presence of sulfuric acid. The materials are heated for distillation in a glass-lined reactor under reflux. The acid is then neutralized with caustic soda and the product is crystallized by cooling. The crystallized product is centrifuged, washed, dried under vacuum, milled and blended, all in corrosion-resistant equipment to avoid metallic contamination.

Acute toxicity

Abdomen-mouse LD50: 960 mg/kg

Flammability hazard characteristics

Combustible, excretes spicy smoke from fireground

Storage

Ventilated , low temperature and dry warehouse.

Production Methods

Methylparaben is prepared by the esterification of p-hydroxybenzoic acid with methanol.

Hazard

Toxic. Use in foods restricted to 0.1%.

Flammability and Explosibility

Nonflammable

Pharmaceutical Applications

Methylparaben is widely used as an antimicrobial preservative in cosmetics, food products, and pharmaceutical formulations; see Table I. It may be used either alone or in combination with other methylparaben is the most frequently used antimicrobial preservative. The parabens are effective over a wide pH range and have a broad spectrum of antimicrobial activity, although they are most effective against yeasts and molds. Antimicrobial activity increases as the chain length of the alkyl moiety is increased, but aqueous solubility decreases; therefore a mixture of parabens is frequently used to provide effective preservation. Preservative efficacy is also improved by the addition of propylene glycol (2–5%), or by using parabens in combination with other antimicrobial agents such as imidurea; Owing to the poor solubility of the parabens, paraben salts (particularly the sodium salt) are more frequently used in formulations. However, this raises the pH of poorly buffered formulations. Methylparaben (0.18%) together with propylparaben (0.02%) has been used for the preservation of various parenteral pharmaceutical formulations;

Biochem/physiol Actions

Methyl 4-hydroxybenzoate, also called methyl paraben or nipagin, comprises the ester of p-hydroxybenzoic acid. It is present naturally in cloudberry, white wine and bourbon vanilla. Methyl 4-hydroxybenzoate has antimicrobial and antifungal functionality and is commercially used as a preservative in the food, cosmetic and pharmaceutical industry. Methyl 4-hydroxybenzoate has cytotoxic effects on keratinocytes in the presence of sunlight. Methyl 4-hydroxybenzoate upon solar irradiation mediates DNA damage and modulates esterase metabolism resulting in skin damage and favors cancer progression. Methyl 4-hydroxybenzoate has estrogenic functionality and upregulates estrogen-related genes.

Safety

Methylparaben and other parabens are widely used as antimicrobial preservatives in cosmetics and oral and topical pharmaceutical formulations. Although parabens have also been used as preservatives in injections and ophthalmic preparations, they are now generally regarded as being unsuitable for these types of formulations owing to the irritant potential of the parabens. These experiences may depend on immune responses to enzymatically formed metabolites of the parabens in the skin. Parabens are nonmutagenic, nonteratogenic, and noncarcinogenic. Sensitization to the parabens is rare, and these compounds do not exhibit significant levels of photocontact sensitization or phototoxicity. Hypersensitivity reactions to parabens, generally of the delayed type and appearing as contact dermatitis, have been reported. However, given the widespread use of parabens as preservatives, such reactions are relatively uncommon; the classification of overstated. Immediate hypersensitivity reactions following injection of preparations containing parabens have also been reported. Delayed-contact dermatitis occurs more frequently when parabens are used topically, but has also been reported to occur after oral administration. Unexpectedly, preparations containing parabens may be used by patients who have reacted previously with contact dermatitis provided they are applied to another, unaffected, site. This has been termed the paraben paradox. Concern has been expressed over the use of methylparaben in infant parenteral products because bilirubin binding may be affected, which is potentially hazardous in hyperbilirubinemic neonates. The WHO has set an estimated total acceptable daily intake for methyl-, ethyl-, and propylparabens at up to 10 mg/kg bodyweight. LD50 (dog, oral): 3.0 g/kg LD50 (mouse, IP): 0.96 g/kg LD50 (mouse, SC): 1.20 g/kg

Carcinogenicity

The carcinogenic potential of methyl paraben has been studied in rodents. Several studies are available, but none that expose animals via oral or dermal routes. No evidence of a carcinogenic effect was observed following intravenous or subcutaneous injection .

storage

Aqueous solutions of methylparaben at pH 3–6 may be sterilized by autoclaving at 120°C for 20 minutes, without decomposition. Aqueous solutions at pH 3–6 are stable (less than 10% decomposition) for up to about 4 years at room temperature, while aqueous solutions at pH 8 or above are subject to rapid hydrolysis (10% or more after about 60 days storage at room temperature);Methylparaben should be stored in a well-closed container in a cool, dry place.

Purification Methods

Fractionally crystallise the ester from its melt, and recrystallise it from *benzene, then from *benzene/MeOH and dry it over CaCl2 in a vacuum desiccator. [Beilstein 10 IV 360.]

Incompatibilities

The antimicrobial activity of methylparaben and other parabens is considerably reduced in the presence of nonionic surfactants, such as polysorbate 80, as a result of micellization.However, propylene glycol (10%) has been shown to potentiate the antimicrobial activity of the parabens in the presence of nonionic surfactants and prevents the interaction between methylparaben and polysorbate 80. Incompatibilities with other substances, such as bentonite, magnesium trisilicate,talc,tragacanth,sodium alginate, essential oils,sorbitol,and atropine,have been reported. It also reacts with various sugars and related sugar alcohols. Absorption of methylparaben by plastics has also been reported; the amount absorbed is dependent upon the type of plastic and the vehicle. It has been claimed that low-density and high-density polyethylene bottles do not absorb methylparaben. Methylparaben is discolored in the presence of iron and is subject to hydrolysis by weak alkalis and strong acids.

Regulatory Status

Methylparaben and propylparaben are affirmed GRAS Direct Food Substances in the USA at levels up to 0.1%. All esters except the benzyl ester are allowed for injection in Japan. In cosmetics, the EU and Brazil allow use of each paraben at 0.4%, but the total of all parabens may not exceed 0.8%. The upper limit in Japan is 1.0%. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (IM, IV, and SC injections; inhalation preparations; ophthalmic preparations; oral capsules, tablets, solutions and suspensions; otic, rectal, topical, and vaginal preparations). Included in medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

InChI:InChI=1/C8H8O3/c1-5-4-6(9)2-3-7(5)8(10)11/h2-4,9H,1H3,(H,10,11)/p-1

Synthetic route

methanol (67-56-1) + 4-hydroxy-benzoic acid (99-96-7) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With boron trifluoride at 65℃; for 0.333333h;	100%
With sulfuric acid for 8h; Heating;	100%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 20℃; Mitsunobu reaction; chemoselective reaction;	100%

methyl 4-acetoxybenzoate (24262-66-6) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
silica gel; toluene-4-sulfonic acid In water; toluene at 80℃; for 6h;	100%
With phosphate buffer In diethyl ether for 2.75h; Ambient temperature; pig liver acetone powder;	100%
With ammonium acetate In methanol at 20℃; for 2.5h;	100%

methanol (67-56-1) + 4-hydroxy-benzaldehyde (123-08-0) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With oxygen at 80℃; under 3750.38 Torr; for 4h; Temperature; Reagent/catalyst; Pressure; Sealed tube;	99.3%
With perchloric acid; sodium percarbonate; vanadia for 1h; Cooling;	98%
With perchloric acid; dihydrogen peroxide; vanadia In water at 5℃; for 2.5h; oxidative esterification;	97%

methyl iodide (74-88-4) + 4-hydroxy-benzoic acid (99-96-7) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With potassium hydrogencarbonate In N,N-dimethyl-formamide at 40℃;	99%
Stage #1: 4-hydroxy-benzoic acid With sodium hydrogencarbonate In water at 20℃; for 1h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0 - 20℃;	95%
With potassium hydroxide at 220℃; im geschlossenen Rohr;
With N'',N'''''-1,8-naphthalenediyl bis[N,N,N',N'-tetramethyl]guanidine In N,N-dimethyl-formamide at 20℃; Kinetics;

methyl 4-(cyanomethoxy)benzoate (137988-24-0) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With hydrogen; platinum(IV) oxide In ethanol	99%

methyl 4-allyloxybenzoate (35750-24-4) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With aniline; (ϖ-allyl)palladium triflate based catalyst at 30℃; for 0.333333h;	99%
With [2,2]bipyridinyl; (1,2-dimethoxyethane)dichloronickel(II); water; bis(pinacol)diborane; lithium tert-butoxide In methanol; N,N-dimethyl acetamide at 30℃; for 24h; Schlenk technique;	95%
With 6,6'-dimethyl-2,2'-bipyridine; (1,2-dimethoxyethane)dichloronickel(II); bis(pinacol)diborane; lithium tert-butoxide In methanol; N,N-dimethyl acetamide; water at 30℃; for 24h; Inert atmosphere; Glovebox; Sealed tube;	95%

4-(tert-butyldimethylsilanyloxy)benzoic acid methyl ester (133642-20-3) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In water; acetonitrile at 20℃; for 0.166667h;	99%
With potassium hydroxide In ethanol at 20℃; for 0.7h;	95%
With sodium phosphate dodecahydrate In N,N-dimethyl-formamide at 20℃; for 2h; chemoselective reaction;	92%

methanol (67-56-1) + carbon monoxide (201230-82-2) + 4-Iodophenol (540-38-5) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With triethylamine at 100℃; under 3750.38 Torr; for 1.5h; Inert atmosphere;	99%
With triethylamine at 80℃; under 3750.38 Torr; for 3h; Autoclave;	75%
With triethylamine; G0-C2 PAMAM dendrimer*PPh2*PdMe2 at 105℃; under 5171.62 Torr; for 19h;	100 % Chromat.

4-carbomethoxyphenyl triflate (17763-71-2) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 1h;	99%
With caesium carbonate In toluene at 80℃; for 15h;	87%
With ammonium acetate; methanol; magnesium; palladium on activated charcoal at 20℃; for 24h;	51%
With (1,2-dimethoxyethane)dichloronickel(II); N-isopropyl-N-tert-butylamine; N-tert-butoxycarbonyl-proline; 4,4'-di-tert-butyl-2,2'-bipyridine In dimethyl sulfoxide at 40℃; for 14h; Irradiation; Sealed tube;	27 %Spectr.

4-benzyloxy-benzoic acid methyl ester (32122-11-5) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With cyclohexa-1,4-diene; 3,6-bis(dimethylamino)-9H-carbazole; caesium carbonate In dimethyl sulfoxide at 23℃; for 44h; Inert atmosphere; Schlenk technique; Irradiation;	99%
With pentamethylbenzene,; boron trichloride In dichloromethane at -78℃; for 0.333333h;	97%
With thiophene; sodium hydrogen sulfate; silica gel for 6h; Heating;	96%

potassium (4-(methoxycarbonyl)phenyl)trifluoroborate (705254-34-8) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With Oxone; water In acetone at 20℃; for 0.0333333h;	99%

4-methoxycarbonylphenylboronic acid (99768-12-4) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In water; acetonitrile at 20℃; for 48h; Reagent/catalyst; Irradiation; Green chemistry;	99%
With N-ethyl-N,N-diisopropylamine In water; acetonitrile for 28h; Irradiation;	99%
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; under 760.051 Torr; for 27h; Irradiation; Green chemistry;	98%

Methyl 4-chlorobenzoate (1126-46-1) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; boric acid; palladium diacetate; caesium carbonate In 1-methyl-pyrrolidin-2-one at 80℃; for 24h; Catalytic behavior; Solvent; Reagent/catalyst; Schlenk technique; Inert atmosphere;	98%
With trans-di(μ-acetato)bis[o-(di-o-tolyl-phosphino)benzyl]dipalladium(II); C29H45Pt; potassium carbonate In water; N,N-dimethyl-formamide at 115℃; for 0.5h; Inert atmosphere; Microwave irradiation;	92%
With tris(6,6'-diamino-2,2'-bipyridine); 4,4-diphenyl-1,3,5,7,8-pentamethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene; Br2Ni*3H2O; water; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 24h; Glovebox; Irradiation; Inert atmosphere;	79%

dihydrogen peroxide (7722-84-1) + 4-methoxycarbonylphenylboronic acid (99768-12-4) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With ammonium bicarbonate In water at 20℃; for 2h; Schlenk technique;	98%

carbonic acid dimethyl ester (616-38-6) + 4-hydroxy-benzoic acid (99-96-7) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With sulfuric acid at 80 - 85℃; for 7.5h; Neat (no solvent); chemoselective reaction;	97.6%
With NaY faujasite at 165℃; for 24h;	87%

dimethyl dicarbonate (4525-33-1) + 4-hydroxy-benzoic acid (99-96-7) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
magnesium(II) perchlorate In nitromethane at 40℃; for 16h;	97%

methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (171364-80-0) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With water; caesium carbonate; hydrazine hydrate at 80℃; for 24h;	97%
With air at 25℃; for 16h; Inert atmosphere;	25 mg
With Oxone; potassium phosphate; naphthalene-2-boronic acid In water at 70℃; for 1h; chemoselective reaction;

4-(tert-butyldimethylsilanyloxy)benzoic acid methyl ester (133642-20-3) + Cs2CO3 → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
In water; N,N-dimethyl-formamide at 20℃; for 1h;	96%

4-(methoxymethoxy)benzoic acid methyl ester (139884-19-8) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
sodium hydrogen sulfate; silica gel In dichloromethane at 20℃; for 1h;	96%

4-allyloxycarbonyloxybenzoic acid methyl ester (1333925-55-5) + 2-propanethiol (75-33-2) → allylisopropyl sulfide (50996-72-0) + carbon dioxide (124-38-9) + methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With Roussin's red salt ester; tetrabutylammomium bromide; potassium hydride In tetrahydrofuran; ethanol at 40℃;	A n/a B n/a C 96%

methanol (67-56-1) + (4-hydroxyphenyl)methanol (623-05-2) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With palladium 10% on activated carbon; oxygen; sodium carbonate at 120℃; under 15001.5 Torr; for 1.5h; Microwave irradiation; Green chemistry;	96%
With sodium carbonate; palladium; silver(l) oxide at 80℃; for 48h; Molecular sieve;	85%
With oxygen at 79.84℃; under 3750.38 Torr; for 12h; Autoclave;

3-iodo-4-methoxy-benzoic acid methyl ester (35387-93-0) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With aluminium trichloride In dichloromethane; ethanethiol for 6.5h; temp. 0 deg C -> RT;	95.1%

4-methoxycarbonylphenyl bromide (619-42-1) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With dicyclohexyl-(2′,4′,6′-triisopropyl-3,6-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine; boric acid; palladium diacetate; caesium carbonate In 1-methyl-pyrrolidin-2-one at 80℃; for 24h; Schlenk technique; Inert atmosphere;	94%
With tris(6,6'-diamino-2,2'-bipyridine); 4,4-diphenyl-1,3,5,7,8-pentamethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene; Br2Ni*3H2O; water; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide; acetonitrile at 20℃; for 24h; Glovebox; Irradiation; Inert atmosphere;	89%
With nickel(II) sulphate; water; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 12h; pH=8.8; UV-irradiation; Inert atmosphere; Glovebox; Enzymatic reaction;	85%

methyl 4-acetoxybenzoate (24262-66-6) → 4-acetyloxy-benzoic acid (2345-34-8) + methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium carbonate; 2-amino-benzenethiol at 100℃; for 0.75h; Hydrolysis;	A 7% B 93%

4-(tert-butoxycarbonyloxy)benzoic acid methyl ester → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With methanol; carbon tetrabromide; triphenylphosphine for 18h; Reflux;	93%
With piperidine In dichloromethane at 20℃; for 4h;	92%

oxygen (80937-33-3) + 4-methoxycarbonylphenylboronic acid (99768-12-4) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With triethanolamine In water at 20℃; for 18h; Sonication; Irradiation; Green chemistry;	93%

Trimethyl orthoacetate (1445-45-0) + 4-hydroxy-benzoic acid (99-96-7) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
microwave irradiation;	92%

methanol (67-56-1) + Ethyl 4-hydroxybenzoate (120-47-8) → methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With lanthanum complex grafted upon hydrotalcite for 8h; pH=10; Reflux;	92%
scandium tris(trifluoromethanesulfonate) at 64℃; for 168h;	81%
With C7H10N2O2*Zn(2+)*2C7H9N2O2(1-)*H2O at 75℃; for 24h; Catalytic behavior;	54 %Spectr.

4-benzoyloxybenzoic acid methyl ester (75915-29-6) → 4-(benzoyloxy)benzoic acid (28547-23-1) + methyl 4-hydroxylbenzoate (99-76-3)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium carbonate; 2-amino-benzenethiol at 100℃; for 0.75h; Hydrolysis; debenzoylation;	A 9% B 91%

benzyl chloride (100-44-7) + methyl 4-hydroxylbenzoate (99-76-3) → 4-benzyloxy-benzoic acid methyl ester (32122-11-5)

Conditions	Yield
With iodide; potassium carbonate In acetone for 7h; Reflux;	100%
With sodium methylate
With sodium ethanolate

methyl 4-hydroxylbenzoate (99-76-3) + allyl bromide (106-95-6) → methyl 4-allyloxybenzoate (35750-24-4)

Conditions	Yield
With potassium carbonate In acetone at 65℃; for 20h;	100%
With potassium carbonate In dimethyl sulfoxide at 20℃; for 8h;	99%
With potassium carbonate In acetone Heating;	89%

methyl 4-hydroxylbenzoate (99-76-3) → methyl 3-bromo-4-hydroxybenzoate (29415-97-2)

Conditions	Yield
With ammonium metavanadate; aluminum tri-bromide; oxygen In 1,4-dioxane at 80℃; for 18h;	100%
With bromine In acetic acid Ambient temperature;	99%
With bromine In dichloromethane at 20℃; for 24h;	95%

1-undecen-11-ylbromide (7766-50-9) + methyl 4-hydroxylbenzoate (99-76-3) → 4-undec-10-enyloxybenzoic acid methyl ester (59100-35-5)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In acetonitrile at 70℃; Inert atmosphere; Stage #2: 1-undecen-11-ylbromide In acetonitrile for 12h; Reflux; Inert atmosphere;	100%
With potassium carbonate In acetone Etherification;	94.9%
With potassium carbonate; potassium iodide In butanone for 12h; Williamson reaction; Reflux;	77.8%
With sodium methylate In methanol Heating;

3,4-dihydro-2H-pyran (110-87-2) + methyl 4-hydroxylbenzoate (99-76-3) → 4-methoxycarbonylphenyl 2-tetrahydropyranyl ether (106342-09-0)

Conditions	Yield
With pyridinium p-toluenesulfonate In acetone for 15h; Ambient temperature;	100%
With pyridinium p-toluenesulfonate In acetone at 20℃;	99%
With 1,5-dichloro-9,10-anthraquinone In dichloromethane for 0.5h; UV-irradiation;	90%

2-(3-bromopropyl)isoindole-1,3-dione (5460-29-7) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-[3-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)propoxy]benzoate (773875-80-2)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 2h; Inert atmosphere; Stage #2: 2-(3-bromopropyl)isoindole-1,3-dione In dimethyl sulfoxide; mineral oil at 20℃; for 3.5h; Time; Inert atmosphere;	100%
Stage #1: methyl 4-hydroxylbenzoate With sodium hydride In dimethyl sulfoxide; mineral oil at 20℃; for 3h; Stage #2: 2-(3-bromopropyl)isoindole-1,3-dione In dimethyl sulfoxide; mineral oil at 20℃; for 70h;	89.3%
With sodium hydride 1.) DMF, 40 deg C, 1 h, 2.) DMF, 90 deg C, 5 h; Yield given. Multistep reaction;

benzyl bromide (100-39-0) + methyl 4-hydroxylbenzoate (99-76-3) → 4-benzyloxy-benzoic acid methyl ester (32122-11-5)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In acetone at 50℃; for 1h; Stage #2: benzyl bromide In acetone at 80℃; for 5h;	100%
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In acetone at 50℃; for 1h; Stage #2: benzyl bromide In acetone at 80℃; for 5h;	100%
With potassium carbonate In acetone at 60℃;	100%

1-dodecylbromide (143-15-7) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-(dodecyloxy)benzoate (40654-49-7)

Conditions	Yield
With potassium carbonate; sodium iodide In acetonitrile for 24h; Heating;	100%
With potassium carbonate In N,N-dimethyl-formamide for 20h; Inert atmosphere; Reflux;	98%
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In acetonitrile at 70℃; Inert atmosphere; Stage #2: 1-dodecylbromide In acetonitrile for 12h; Reflux; Inert atmosphere;	96%

trifluoromethylsulfonic anhydride (358-23-6) + methyl 4-hydroxylbenzoate (99-76-3) → 4-carbomethoxyphenyl triflate (17763-71-2)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere;	100%
With pyridine In dichloromethane at 0 - 20℃; for 1h;	98%
With N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - 0℃;	96%

methyl 4-hydroxylbenzoate (99-76-3) + propargyl bromide (106-96-7) → methyl 4-(2-propynoxy)benzoate (98260-05-0)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In acetone; toluene for 72h; Reflux;	100%
With potassium carbonate In acetone Inert atmosphere;	99%
With potassium carbonate In acetone at 65℃; for 18h; Inert atmosphere;	98%

methyl 4-hydroxylbenzoate (99-76-3) + cyanomethyl bromide (590-17-0) → methyl 4-(cyanomethoxy)benzoate (137988-24-0)

Conditions	Yield
With potassium carbonate In acetone Heating;	100%
With potassium carbonate In acetone at 20℃;	95.8%

methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-hydroxycyclohexanecarboxylate (3618-03-9, 6125-57-1, 17449-76-2)

Conditions	Yield
With hydrogen; rhodium on aluminium In ethanol under 2327.2 Torr; for 96h;	100%
With hydrogen; Rh/Al2O3 In methanol under 2844.3 Torr; for 18h;	98%
With hydrogen; Rh on carbon In tetrahydrofuran under 76000 Torr; for 18h;	98%

1-bromo dodecane (112-29-8) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-decyloxybenzoate (62443-10-1)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In acetonitrile at 70℃; Inert atmosphere; Stage #2: 1-bromo dodecane In acetonitrile for 12h; Reflux; Inert atmosphere;	100%
With potassium carbonate In N,N-dimethyl-formamide for 20h; Inert atmosphere; Reflux;	96%
With potassium carbonate In acetonitrile for 12h; Reflux;	96%

2-(N-tert-butoxycarbonylamino)ethanol (26690-80-2) + methyl 4-hydroxylbenzoate (99-76-3) → 4-(2-tert-butoxycarbonylaminoethoxy)benzoic acid methyl ester (174666-16-1)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; for 20h; Condensation;	100%
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 5h;
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran for 5.16h;
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; for 17h; Cooling with ice;	0.45 g

methyl 4-hydroxylbenzoate (99-76-3) + 4-(2-hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester (89151-44-0) → methyl 4-(2-N-BOC-piperidin-4-ylethoxy)benzoate (163209-93-6)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; for 20h; Condensation;	100%
With triphenylphosphine tagged with poly-(ethyleneglycol)-ω-monomethyl ether; diethyl azodicarboxylate tagged with poly-(ethyleneglycol)-ω-monomethyl ether In tetrahydrofuran for 20h; Mitsunobu reaction; Inert atmosphere;

methyl 4-hydroxylbenzoate (99-76-3) + 3-(4-nitro)-benzoyl-2(3H)-benzothiazolone (187409-84-3) → 4-(4-nitro-benzoyloxy)-benzoic acid methyl ester (79859-22-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	100%

(S)-1-bromo-3,7-dimethyloctane (3383-83-3, 59965-20-7, 72746-96-4, 79434-89-2) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-((S)-3,7-dimethyloctyloxy) benzoate (886761-14-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 4h; Inert atmosphere;	100%
With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 4h; Inert atmosphere;	100%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 13h;	94%
With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 110℃; Williamson etherification;

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-(2-morpholinoethoxy)benzoate (92501-87-6)

Conditions	Yield
With potassium carbonate In acetonitrile at 50℃;	100%
With caesium carbonate In acetonitrile at 80 - 85℃; for 4h; Inert atmosphere;	92%
With potassium carbonate In acetone Heating;

methyl 4-hydroxylbenzoate (99-76-3) + isopropyl bromide (75-26-3) → methyl 4-isopropoxybenzoate (35826-59-6)

Conditions	Yield
With potassium carbonate In acetone for 72h; Inert atmosphere; Reflux;	100%
With potassium carbonate In acetone for 72h; Inert atmosphere; Reflux;	100%
With potassium carbonate In acetone at 85℃; for 72h; Sealed tube;	94.7%
With sodium hydride In N,N-dimethyl-formamide at 60℃;	80%

chloroacetonitrile (107-14-2) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-(cyanomethoxy)benzoate (137988-24-0)

Conditions	Yield
With potassium carbonate; sodium iodide In acetone at 20 - 60℃; for 88h;	100%
With potassium carbonate; sodium iodide In acetone at 20 - 60℃; for 88h;	100%
With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 4h;	98%

1-(tert-butoxycarbonyl)-(5R)-isopropyl-(2S)-pyrrolidinylmethanol + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-(1-(tert-butoxycarbonyl)-(5R)-isopropyl-(2S)-pyrrolidinylmethoxy)benzoate

Conditions	Yield
With diisopropyl (E)-azodicarboxylate; triphenylphosphine In tetrahydrofuran; hexane; ethyl acetate	100%

4-(2-chloroethyl)morpholine hydrochride (3647-69-6) + methyl 4-hydroxylbenzoate (99-76-3) → 4-(2-morpholin-4-yl-ethoxy)-benzoic acid (134599-45-4)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In DMF (N,N-dimethyl-formamide) at 100℃; Stage #2: 4-(2-chloroethyl)morpholine hydrochride In DMF (N,N-dimethyl-formamide) at 100℃; for 2h;	100%

methyl 4-hydroxylbenzoate (99-76-3) + 3-chloroprop-1-ene (107-05-1) → methyl 4-allyloxybenzoate (35750-24-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 50℃;	100%
With potassium carbonate In N,N-dimethyl-formamide at 50℃;	100%
With potassium carbonate In N,N-dimethyl-formamide at 50℃;	99%
Stage #1: methyl 4-hydroxylbenzoate With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.333333h; Inert atmosphere; Stage #2: 3-chloroprop-1-ene In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;	87%
With potassium carbonate In N,N-dimethyl-formamide at 80℃;	85.7%

10-bromodec-1-ene (62871-09-4) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-(dec-9-enyloxy)benzoate (117560-76-6)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With potassium carbonate In acetonitrile at 70℃; Inert atmosphere; Stage #2: 10-bromodec-1-ene In acetonitrile for 12h; Reflux; Inert atmosphere;	100%

methyl 4-hydroxylbenzoate (99-76-3) + 1-Bromo-2-butyne (3355-28-0) → methyl 4-(but-2-yn-1-yloxy)benzoate (362705-52-0)

Conditions	Yield
With potassium carbonate In butanone at 20℃; for 23h; Reflux;	100%
With potassium carbonate In butanone at 20℃; for 23h; Reflux;	100%
Stage #1: methyl 4-hydroxylbenzoate With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: 1-Bromo-2-butyne In N,N-dimethyl-formamide; mineral oil at 19℃; for 20h; Inert atmosphere;	79%

2-Methoxyethoxymethyl chloride (3970-21-6) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-((2-methoxyethoxy)methoxy)benzoate (906672-79-5)

Conditions	Yield
Stage #1: methyl 4-hydroxylbenzoate With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 2-Methoxyethoxymethyl chloride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 24h;	100%
Stage #1: methyl 4-hydroxylbenzoate With sodium hydride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 2-Methoxyethoxymethyl chloride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 24h;	100%

methyl 4-hydroxylbenzoate (99-76-3) + 3,4-dichlorobenzyl bromide (18880-04-1) → 4-(3,4-dichloro-benzyloxy)-benzoic acid methyl ester (84404-04-6)

Conditions	Yield
With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 48h;	100%
With potassium carbonate In acetone at 65 - 80℃; for 5h;
With potassium carbonate In acetone at 80℃; for 5h;

2,3,4,6-tetra-O-acetyl-d-glucopyranosyl trichloroacetimidate (74808-10-9, 86520-63-0, 87119-53-7, 92052-29-4, 121238-27-5, 127061-80-7, 142831-80-9) + methyl 4-hydroxylbenzoate (99-76-3) → 4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (74950-95-1)

Conditions	Yield
Stage #1: 2,3,4,6-tetra-O-acetyl-d-glucopyranosyl trichloroacetimidate; methyl 4-hydroxylbenzoate In dichloromethane at 0℃; for 0.166667h; Molecular sieve; Inert atmosphere; Stage #2: With boron trifluoride diethyl etherate In dichloromethane for 3h; Molecular sieve; Inert atmosphere;	100%

Upstream product

• 143925-57-9 1-[(Benzyl-trimethylsilanylmethyl-carbamoyl)-methyl]-4-oxo-cyclohexa-2,5-dienecarboxylic acid methyl ester 
• 3943-97-3 methyl 4-hydroxycinnamate 
• 18826-95-4 1.3-butanediol 
• 28141-24-4 4-hydroxybenzoyl chloride 
• 109-88-6 magnesium methanolate 
• 77-78-1 dimethyl sulfate 
• 99-96-7 4-hydroxy-benzoic acid 
• 74-88-4 methyl iodide 
• 67-56-1 methanol 
• 186581-53-3 diazomethane 
• 2382-96-9 benzo[d]oxazole-2-(3H)-thione 
• 2983-74-6 4-methoxyphenyl cyanate 
• 61846-10-4 7-Oxabicyclo<4.1.0>hept-4-en-1,4-dicarbonsaeure-dimethylester 
• 121-98-2 methyl 4-methoxybenzoate 

Downstream Products

• 1711-24-6 4-(2-hydroxyethoxy)benzoic acid 
• 92501-87-6 methyl 4-(2-morpholinoethoxy)benzoate 
• 24262-66-6 methyl 4-acetoxybenzoate 
• 109470-61-3 4-(methoxycarbonyl)phenyl 3,4,5-trimethoxybenzoate 
• 1486-51-7 p-(benzyloxy)benzoic acid 
• 32122-11-5 4-benzyloxy-benzoic acid methyl ester 
• 75915-29-6 4-benzoyloxybenzoic acid methyl ester 
• 5438-19-7 4-propoxybenzoic acid 
• 115478-59-6 methyl 4-propoxy benzoate 
• 104097-41-8 4-sec-butoxy-benzoic acid 
• 69076-29-5 4-(3-chloropropoxy)benzoic acid methyl ester 
• 35005-30-2 methyl 4-(2-methoxy-2-oxoethoxyl)benzoate 
• 105653-04-1 succinic acid bis-(4-methoxycarbonyl-phenyl ester) 
• 30762-06-2 4-(2-phenylethyloxy)benzoic acid 

Relevant academic research and scientific papers

A Mild Heteroatom (O -, N -, and S -) Methylation Protocol Using Trimethyl Phosphate (TMP)-Ca(OH) 2Combination

A mild heteroatom methylation protocol using trimethyl phosphate (TMP)-Ca(OH)2combination has been developed, which proceeds in DMF, or water, or under neat conditions, at 80 °C or at room temperature. A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, are suitable substrates for this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmentally friendly nature of this protocol make it an attractive alternative to the conventional base-promoted heteroatom methylation procedures.

Carboxyl Methyltransferase Catalysed Formation of Mono- and Dimethyl Esters under Aqueous Conditions: Application in Cascade Biocatalysis

Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono- and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl-l-tyrosine, trans, trans-muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5–6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5-hydroxymethylfurfural (HMF).

Discovery and characterization of a novel perylenephotoreductant for the activation of aryl halides

To develop a photocatalyst with catalytical activity for substrates with low reactivities is always highly desired. Herein, based on the principle of structure–property relationships, we rationally designed the natural product cercosporin, the naturally occurring perylenequinonoid pigment, to develop a novel organic perylenephotoreductant, hexacetyl reduced cercosporin (HARCP), through structural manipulation. Compared with cercosporin, HARCP shows prominent electrochemical and photophysical characteristics with greatly improved photoreductive activity, fluorescence lifetime and fluorescence quantum yield. These properties allowed HARCP as a powerful photoreductant to efficiently realize a series of benchmark reactions, including photoreduction, alkoxylation and hydroxylation to construct C–H and C–O bonds using aryl halides as substrates under mild conditions, all of which have never been achieved by the same photocatalyst. Thus, this study well supports the notion that the principle between structural manipulation and photocatalytic activity is of great significance to design customized photocatalysts for photoredox chemistry.

Biocatalytic Cross-Coupling of Aryl Halides with a Genetically Engineered Photosensitizer Artificial Dehalogenase

Devising artificial photoenzymes for abiological bond-forming reactions is of high synthetic value but also a tremendous challenge. Disclosed herein is the first photobiocatalytic cross-coupling of aryl halides enabled by a designer artificial dehalogenase, which features a genetically encoded benzophenone chromophore and site-specifically modified synthetic NiII(bpy) cofactor with tunable proximity to streamline the dual catalysis. Transient absorption studies suggest the likelihood of energy transfer activation in the elementary organometallic event. This design strategy is viable to significantly expand the catalytic repertoire of artificial photoenzymes for useful organic transformations.

Hydroxyl radical-mediated oxidative cleavage of CC bonds and further esterification reaction by heterogeneous semiconductor photocatalysis

A hydroxyl radical-mediated aerobic cleavage of alkenes and further sequence esterification reaction for the preparation of carbonyl compounds have been developed by using tubular carbon nitride (TCN) as a general heterogeneous photocatalyst under an oxygen atmosphere with visible light irradiation. This protocol has an excellent substrate scope and gives the desired aldehydes, ketones and esters in moderate to high yields. Importantly, this metal-free procedure employed photogenerated hydroxyl radicals in situ as green oxidation active species, avoiding the present additional initiators. The reaction could be carried out under solar light irradiation and was applicable to large-scale reactions. Furthermore, the recyclable TCN catalyst could be used several times without a significant loss of activities.

Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes**

The facile production of ArCF2X and ArCX3 from ArCF3 using catalytic iron(III)halides is reported, which constitutes the first iron-catalyzed halogen exchange for non-aromatic C?F bonds. Theoretical calculations suggest direct activation of C?F bonds by iron coordination. ArCX3 and ArCF2X products of the reaction are synthetically valuable due to their diversification potential. In particular, chloro- and bromodifluoromethyl arenes (ArCF2Cl, ArCF2Br respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF2R). To optimize for mono-halogen exchange, a statistical method called Design of Experiments was used. Optimized parameters were successfully applied to electron rich and electron deficient aromatic substrates, and to the late stage diversification of flufenoxuron, a commercial insecticide. These methods are highly practical, being run at convenient temperatures and using inexpensive common reagents.

Coordination Polymers as a Functional Material for the Selective Molecular Recognition of Nitroaromatics and ipso-Hydroxylation of Arylboronic Acids

We report the synthesis and structural characterization of two coordination polymers (CPs), namely; [{Zn(L)(DMF)4} ? 2BF4]α (1) and [{Cd(L)2(Cl)2} ? 2H2O]α (2) (where L=N2,N6-di(pyridin-4-yl)naphthalene-2,6-dicarboxamide). Crystal packing of 1 reveals the existence of channels running along the b- and c-axis filled by the ligated DMF and lattice anions, respectively. Whereas, crystal packing of 2 reveals that the metallacycles of each 1D chain are intercalating into the groove of adjacent metallacycles resulting in the stacking of 1D loop-chains to form a sheet-like architecture. In addition, both 1 and 2 were exploited as multifunctional materials for the detection of nitroaromatic compounds (NACs) as well as a catalyst in the ipso-hydroxylation of aryl/heteroarylboronic acids. Remarkably, 1 and 2 showed high fluorescence stability in an aqueous medium and displayed a maximum 88% and 97% quenching efficiency for 4-NPH, respectively among all the investigated NACs. The mechanistic investigation of NACs recognition suggested that the fluorescence quenching occurred via electron as well as energy transfer process. Furthermore, the ipso-hydroxylation of aryl/heteroarylboronic acids in presence of 1 and 2 gave up to 99% desired product yield within 15 min in our established protocol. In both cases, 1 and 2 are recyclable upto five cycles without any significant loss in their efficiency.

Isotruxene-based porous polymers as efficient and recyclable photocatalysts for visible-light induced metal-free oxidative organic transformations

Two new isotruxene-based porous polymers were prepared and demonstrated to be highly efficient, metal-free heterogeneous photocatalysts for oxidative transformations using air as the mild oxidant under visible-light irradiation. Both catalysts show excellent recyclability. In addition, the reactions can be performed in water, further indicating the greenness of this method. This journal is

Building a Pyrazole–Benzothiadiazole–Pyrazole Photosensitizer into Metal–Organic Frameworks for Photocatalytic Aerobic Oxidation

Charge separation plays a crucial role in regulating photochemical properties and therefore warrants consideration in designing photocatalysts. Metal–organic frameworks (MOFs) are emerging as promising candidates for heterogeneous photocatalysis due to their structural designability and tunability of photon absorption. Herein, we report the design of a pyrazole–benzothiadiazole–pyrazole organic molecule bearing a donor–acceptor–donor conjugated π-system for fast charge separation. Further attempts to integrate such a photosensitizer into MOFs afford a more effective heterogeneous photocatalyst (JNU-204). Under visible-light irradiation, three aerobic oxidation reactions involving different oxygenation pathways were achieved on JNU-204. Recycling experiments were conducted to demonstrate the stability and reusability of JNU-204 as a robust heterogeneous photocatalyst. Furthermore, we illustrate its applications in the facile synthesis of pyrrolo[2,1-a]isoquinoline-containing heterocycles, core skeletons of a family of marine natural products. JNU-204 is an exemplary MOF platform with good photon absorption, suitable band gap, fast charge separation, and extraordinary chemical stability for proceeding with aerobic oxidation reactions under visible-light irradiation.

A Dual-Function Highly Crystalline Covalent Organic Framework for HCl Sensing and Visible-Light Heterogeneous Photocatalysis

Covalent organic frameworks (COFs) offer great potential for various advanced applications such as photocatalysis, sensing, and so on because of their fully conjugated, porous, and chemically stable unique structural architecture. In this work, we have designed and developed a truxene-based ultrastable COF (Tx-COF-2) by Schiff-base condensation between 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 5,5,10,10,15,15-hexamethyl-10,15-dihydro-5H-diindeno(1,2-a:1′,2′-c)fluorene-2,7,12-tricarbaldehyde (Tx-CHO) for the first time. The resulting COF possesses excellent crystallinity, permanent porosity, and high Brunauer-Emmett-Teller (BET) surface areas (up to 1137 m2 g-1). The COF was found to be a heterogeneous, recyclable photocatalyst for efficient conversion of arylboronic acids to phenols under visible-light irradiation, an environmentally friendly alternative approach to conventional metal-based photocatalysis. Besides, Tx-COF-2 provides an immediate naked-eye color change (1 s) and fluorescence "turn-on"phenomena upon exposure to HCl. The response is highly sensitive, with an ultralow detection limit of up to 4.5 nmol L-1.