603-41-8

Basic information

• Product Name: p,p'-(2-pyridylmethylene)bisphenol
• Synonyms: p,p'-(2-pyridylmethylene)bisphenol;dihydroxydiphenyl-pyridyl methane;4,4''-(2-PYRIDINYLMETHYLENE)BISPHENOL;4,4'-Dihydroxydiphenyl(2-pyridyl)methane;Bis(4-hydroxyphenyl)(2-pyridyl)methane;DDPM (pharmaceutical);La 96;4,4'-(2-Pyridylmethylene)bisphenol
• CAS NO: 603-41-8
• Molecular Formula: C₁₈H₁₅NO₂
• Molecular Weight: 277.3172
• EINECS: 210-039-7
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 603-41-8.mol
• Article Data: 16

Chemical Properties

• Melting Point: >200°C (dec.)
• Boiling Point: 462.1 °C at 760 mmHg
• Flash Point: 233.3 °C
• Appearance: /
• Density: 1.244 g/cm³
• Storage Temp.: Refrigerator, Under Inert Atmosphere
• PKA: 9.71±0.10(Predicted)
• CAS DataBase Reference: p,p'-(2-pyridylmethylene)bisphenol(CAS DataBase Reference)
• NIST Chemistry Reference: p,p'-(2-pyridylmethylene)bisphenol(603-41-8)
• EPA Substance Registry System: p,p'-(2-pyridylmethylene)bisphenol(603-41-8)

Safety Data

• Hazardous Substances Data: 603-41-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 603-41-8 differently. You can refer to the following data:
1. The active form of Bisacodyl. Cathartic.
2. The active form of Bisacodyl. Cathartic

Synthetic route

3,3'-dichloro-4,4'-(pyridin-2-ylmethylene)diphenol → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With nickel aluminum; sodium hydroxide at 20℃; for 9h; Concentration;	95.7%

bisacodyl (603-50-9) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With potassium hydroxide In ethanol; water at 20℃; for 72h;	92%
With sodium hydroxide In water; acetonitrile at 50℃; for 5h; Temperature;	10.99 g

3-(4-methoxyphenyl)-[1,2,3]triazolo[1,5-a]pyridine (78539-92-1) + (4-((tert-butyldimethylsilyl)oxy)phenyl)boronic acid (159191-56-7) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Stage #1: 3-(4-methoxyphenyl)-[l,2,3]triazolo[1,5-a]pyridine; (4-((tert-butyldimethylsilyl)oxy)phenyl)boronic acid With potassium carbonate In benzene at 20℃; for 10h; UV-irradiation; Stage #2: With hydrogen bromide; acetic acid Reflux;	80%

pyridine-2-carbaldehyde (1121-60-4) + phenol (108-95-2) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With sulfuric acid at 0 - 20℃; for 3h;	71.1%
Stage #1: phenol With sulfuric acid; alpha cyclodextrin at 20℃; Large scale; Stage #2: pyridine-2-carbaldehyde Large scale;	59.4%
With sulfuric acid

4-hydroxyphenyl(2-pyridyl) carbinol (33455-95-7) + phenol (108-95-2) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With phosphoric acid In water at 100℃; for 0.5h;	69%

4,4'-(pyridin-2-ylmethylene)dianiline (85171-91-1) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With sulfuric acid; sodium nitrite

di[4'',4'''-di(methoxy)phenyl](2'-pyridyl)methanol (67916-54-5) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With hydrogen iodide
With hydrogen iodide; acetic acid at 100℃; for 6h; Reagent/catalyst; Large scale;	1.6 kg

bis-(4-methoxy-phenyl)-[2]pyridyl-acetonitrile (94871-89-3) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With hydrogen bromide Erwaermen des Reaktionsprodukts mit wss.Kalilauge;

2-diethoxymethyl-pyridine (27443-37-4) + phenol (108-95-2) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With sulfuric acid
With sulfuric acid

phenol (108-95-2) + sodium-salt of/the/ hydroxy-<2>pyridyl-methanesulfonic acid → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With sulfuric acid
With sulfuric acid

pyridine-2-carbonyl chloride (29745-44-6) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 8.4 g / triethylamine / CH2Cl2 / 0 - 20 °C 2: 56 percent / AlCl3 / 4 h / 160 °C 3: 94.5 percent / sodium borohydride / methanol / 2 h / 0 - 20 °C 4: 69 percent / H3PO4 / H2O / 0.5 h / 100 °C View Scheme

2-Picolinic acid (98-98-6) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: thionyl chloride / benzene / 12 h / Heating 2: 8.4 g / triethylamine / CH2Cl2 / 0 - 20 °C 3: 56 percent / AlCl3 / 4 h / 160 °C 4: 94.5 percent / sodium borohydride / methanol / 2 h / 0 - 20 °C 5: 69 percent / H3PO4 / H2O / 0.5 h / 100 °C View Scheme

pyridine-2-carboxylic acid phenyl ester (26838-86-8) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 56 percent / AlCl3 / 4 h / 160 °C 2: 94.5 percent / sodium borohydride / methanol / 2 h / 0 - 20 °C 3: 69 percent / H3PO4 / H2O / 0.5 h / 100 °C View Scheme

(4-hydroxyphenyl)(pyridin-2-yl)methanone (33077-70-2) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 94.5 percent / sodium borohydride / methanol / 2 h / 0 - 20 °C 2: 69 percent / H3PO4 / H2O / 0.5 h / 100 °C View Scheme

pyridine-2-carbaldehyde (1121-60-4) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride 2: sulfuric acid; sodium nitrite View Scheme

2-pyridyllithium (17624-36-1) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether / -65 - -40 °C 2: aqueous hydriodic acid View Scheme

bis(p-methoxyphenyl)methanone (90-96-0) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether / -65 - -40 °C 2: aqueous hydriodic acid View Scheme

aniline (62-53-3) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride 2: sulfuric acid; sodium nitrite View Scheme

1-bromo-4-methoxy-benzene (104-92-7) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium / tetrahydrofuran / 1 h / 20 - 65 °C / Inert atmosphere; Large scale 1.2: 4 h / 10 - 20 °C / Inert atmosphere; Large scale 2.1: hydrogen iodide; acetic acid / 6 h / 100 °C / Large scale View Scheme

ethyl-2-picolinate (2524-52-9) → 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium / tetrahydrofuran / 1 h / 20 - 65 °C / Inert atmosphere; Large scale 1.2: 4 h / 10 - 20 °C / Inert atmosphere; Large scale 2.1: hydrogen iodide; acetic acid / 6 h / 100 °C / Large scale View Scheme

Guttalax (10040-45-6) → 4-((4-hydroxyphenyl)(pyridin-2-yl)methyl)phenyl hydrogen sulfate (51264-33-6) + 4,4'-(2-pyridylmethylene)diphenol (603-41-8)

Conditions	Yield
With water at 40℃; for 730.5h;

Guttalax (10040-45-6) → 4-((4-hydroxyphenyl)(pyridin-2-yl)methyl)phenyl hydrogen sulfate (51264-33-6) + 4,4'-(2-pyridylmethylene)diphenol (603-41-8) + (hydroxy(pyridin-2-yl)methylene)bis(4,1-phenylene) bis(sulfate)

Conditions	Yield
With water at 40℃; for 4383h; Temperature;

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + acetic anhydride (108-24-7) → bisacodyl (603-50-9)

Conditions	Yield
With sodium acetate at 100 - 140℃; Temperature; Large scale;	95%
With pyridine In dichloromethane at 0 - 20℃; for 2h;	88%
With sodium acetate
With pyridine
With sodium acetate

4,4'-(2-pyridylmethylene)diphenol (603-41-8) → Guttalax (10040-45-6)

Conditions	Yield
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With pyridine; chlorosulfonic acid at 0 - 20℃; for 5h; Stage #2: With sodium hydroxide Concentration; Cooling with ice;	86.4%
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With pyridine; chlorosulfonic acid at 10 - 25℃; for 12h; Inert atmosphere; Large scale; Stage #2: With water; sodium hydroxide at 0℃; pH=11; pH-value; Inert atmosphere; Large scale;	2.1 kg

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + 8-tosyloxy-3,6-dioxaoctanol (77544-68-4) → 2,2′-(((((((pyridin-2-ylmethylene)bis(4,1-phenylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))diethanol

Conditions	Yield
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere; Stage #2: 8-tosyloxy-3,6-dioxaoctanol In N,N-dimethyl-formamide at 80℃; for 96h; Inert atmosphere;	70%

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + 5-tosyloxy-3-oxapentanol (118591-58-5) → 2,2′-(((((pyridin-2-ylmethylene)bis(4,1-phenylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy)) diethanol

Conditions	Yield
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere; Stage #2: 5-tosyloxy-3-oxapentanol In N,N-dimethyl-formamide at 80℃; for 96h; Inert atmosphere;	60%

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + p-toluenesulfonic acid 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl ester (77544-60-6) → 2,2′-(((((((((pyridin-2-ylmethylene)bis(4,1-phenylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))diethanol

Conditions	Yield
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere; Stage #2: p-toluenesulfonic acid 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl ester In N,N-dimethyl-formamide at 80℃; for 96h; Inert atmosphere;	50%

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + 2-bromoethanol (540-51-2) → 2,2′-(((pyridin-2-ylmethylene)bis(4,1-phenylene))bis(oxy))diethanol + 4-((4-(2-hydroxyethoxy)phenyl)(pyridin-2-yl)methyl)phenol

Conditions	Yield
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 0.5h; Inert atmosphere; Stage #2: 2-bromoethanol With potassium iodide In N,N-dimethyl-formamide at 80℃; for 96h; Inert atmosphere;	A 15% B 50%

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + 2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate (155130-15-7) → 14,14′-(((pyridin-2-ylmethylene)bis(4,1-phenylene))bis(oxy))bis(3,6,9,12-tetraoxatetradecan-1-ol)

Conditions	Yield
Stage #1: 4,4'-(2-pyridylmethylene)diphenol With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere; Stage #2: 2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethyl 4-methylbenzenesulfonate In N,N-dimethyl-formamide at 80℃; for 96h; Inert atmosphere;	45%

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + dimethyl sulfate (77-78-1) → 2-(4,4'-dihydroxy-benzhydryl)-1-methyl-pyridinium; methyl sulfate

Conditions	Yield
With tetrahydrofuran

4,4'-(2-pyridylmethylene)diphenol (603-41-8) → 2-(4,4'-dihydroxy-benzhydryl)-piperidine

Conditions	Yield
With acetic acid; platinum at 40℃; Hydrogenation;
With ethanol; nickel at 100℃; under 73550.8 Torr; Hydrogenation;

4,4'-(2-pyridylmethylene)diphenol (603-41-8) + allyl bromide (106-95-6) → C24H23NO2

Conditions	Yield
With potassium carbonate In acetone

4,4'-(2-pyridylmethylene)diphenol (603-41-8) → C24H23NO2

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / acetone 2: BCl3 / CH2Cl2 View Scheme

Upstream product

• 78539-92-1 3-(4-methoxyphenyl)-[l,2,3]triazolo[1,5-a]pyridine 
• 159191-56-7 (4-((tert-butyldimethylsilyl)oxy)phenyl)boronic acid 
• 728-87-0 4,4'-Dimethoxybenzhydrol 
• 102237-74-1 4-(bis(4-methoxyphenyl)methyl)pyridine 
• 603-50-9 bisacodyl 
• 10040-45-6 Guttalax 
• 2524-52-9 ethyl-2-picolinate 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 62-53-3 aniline 
• 90-96-0 bis(p-methoxyphenyl)methanone 
• 17624-36-1 2-pyridyllithium 
• 1121-60-4 pyridine-2-carbaldehyde 
• 33077-70-2 (4-hydroxyphenyl)(pyridin-2-yl)methanone 
• 26838-86-8 pyridine-2-carboxylic acid phenyl ester 

Downstream Products

• 10040-45-6 Guttalax 
• 603-50-9 bisacodyl 

Relevant articles and documents

Preparation method of bisacodyl

The present invention provides the preparation method shown in formula I., the preparation method of bisacodyl. The present invention provides a new method for the preparation of bisacodyl.

Method for preparing high-purity sodium picosulfate intermediate and sodium picosulfate

The invention discloses a method for preparing high-purity sodium picosulfate and an intermediate thereof. The method comprises the following steps: (1) dropwise adding concentrated sulfuric acid and 2-pyridylaldehyde into an acetonitrile solution of phenol in sequence for reaction; (2) adjusting to be alkaline after reaction quenching, neutralizing, dispersing and crystallizing, and refining a crude product by using organic alcohol; (3) adding the intermediate into a pyridine solution of chlorosulfonic acid, washing off pyridine by using acetone after the reaction is finished, treating into sodium salt by using an alkali, concentrating until dryness, extracting by using hot methanol, adding ethyl acetate for crystallization, filtering and drying to obtain a sodium picosulfate crude product; and (4) thermally extracting the crude product with absolute ethyl alcohol, adding a proper amount of purified water, cooling and crystallizing to obtain the sodium picosulfate monohydrate. According to the method, the high-purity intermediate and the sodium picosulfate monohydrate can be stably obtained by controlling the content of the isomer in the intermediate.

Synthesis method of sodium picosulfate

The method comprises the following steps: adding acridine to an organic solvent, adding basic substances for reaction, adjusting pH values, filtering to obtain 4 and 4' - (2 -pyridylmethyl) bisphenol. 4, 4' - (2 - Picoline) bisphenol was added to the reaction solvent, a basic substance was added, and then a sulfonating reagent was added for the reaction. After the completion of the reaction, the crude product is obtained by quenching, extraction, concentration and recrystallization. The crude product was recrystallized from sodium sulfate to give a qualified sodium sulfate product. The method has the advantages that the process route is simple, the operation is simpler, the yield is increased and the like, the purity of the intermediate produced by the method is high, and the sodium metabisulfite meeting the requirements of the pharmacopeia can be easily obtained to solve the defects caused by the prior art.