118292-06-1

Basic information

• Product Name: 6-Ethynyl-4,4-dimethylthiochroman
• Synonyms: 6-Ethynyl-4,4-dimethyl-thiochroman;4,4-DIMETHYL-6-ETHYNYLTHIOCHROMAN;6-Ethynyl-3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran;6-ethynyl-4,4-diMethyl-3,4-dihydro-2H-1-benzothiopyran;2H-1-Benzothiopyran,6-ethynyl-3,4-dihydro-4,4-diMethyl-;Tazarotene IMpurity (6-Ethynyl-4,4-DiMethyl ThiochroMan)
• CAS NO: 118292-06-1
• Molecular Formula: C₁₃H₁₄S
• Molecular Weight: 202.32
• Product Categories: Pharmaceutical Intermediates
• Mol File: 118292-06-1.mol
• Article Data: 12

Chemical Properties

• Melting Point: 69-72 °C
• Boiling Point: 299 °C
• Flash Point: 128 °C
• Appearance: /
• Density: 1.09
• Vapor Pressure: 0.002mmHg at 25°C
• Refractive Index: 1.597
• Storage Temp.: 2-8°C
• CAS DataBase Reference: 6-Ethynyl-4,4-dimethylthiochroman(CAS DataBase Reference)
• NIST Chemistry Reference: 6-Ethynyl-4,4-dimethylthiochroman(118292-06-1)
• EPA Substance Registry System: 6-Ethynyl-4,4-dimethylthiochroman(118292-06-1)

Safety Data

• Hazardous Substances Data: 118292-06-1(Hazardous Substances Data)

Usage

Description

6-Ethynyl-4,4-dimethylthiochroman is a chemical compound characterized by its unique structure, which features an ethynyl group at the 6th position and two methyl groups attached to the 4th carbon atom of the chroman ring. The presence of a thiochromene ring further distinguishes this compound, making it a versatile molecule with potential applications in various fields.

Uses

Used in Chemical Synthesis:
6-Ethynyl-4,4-dimethylthiochroman is used as a key intermediate in the preparation of alkynyl aryl iodides through copper-catalyzed three-component carboiodination of arynes. This process is significant in the field of organic chemistry, as it allows for the synthesis of complex molecular structures with potential applications in pharmaceuticals, materials science, and other areas.
In the Pharmaceutical Industry:
6-Ethynyl-4,4-dimethylthiochroman may be used as a building block for the development of novel pharmaceutical compounds. Its unique structure could be exploited to design new drugs with specific biological activities, targeting various diseases and conditions.
In the Materials Science Industry:
The compound's structural properties may also make it a candidate for the development of new materials with unique properties, such as improved conductivity, stability, or reactivity. This could have implications for the design of advanced materials for use in electronics, energy storage, or other high-tech applications.
In the Research and Development Sector:
6-Ethynyl-4,4-dimethylthiochroman can be utilized as a research tool to study the reactivity and properties of similar compounds. Understanding the behavior of this molecule in various chemical reactions can provide valuable insights into the design and synthesis of new molecules with tailored properties and applications.

InChI:InChI=1/C13H14S/c1-4-10-5-6-12-11(9-10)13(2,3)7-8-14-12/h1,5-6,9H,7-8H2,2-3H3

Synthetic route

6-(1,1-dichloroethyl)-4,4-dimethylthiochroman (1187617-88-4) → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -5 - 35℃; Product distribution / selectivity;	90%

3-[4,4-dimethylthiochroman-6-yl]-3-chloro-2-propene-1-al → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 80 - 90℃; for 2h; Vilsmeier Hack reaction;	87.68%
With sodium hydroxide In 1,4-dioxane; water at 80 - 90℃; for 2h;	87.68%
With sodium hydroxide In 1,4-dioxane; water at 80 - 90℃; for 2h;	87.68%

4,4-dimethyl-6-ethynylthiochromane S-oxide (864841-55-4) → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
With N,N-dimethyl-formamide; phosphorus trichloride at -20℃; for 1h;	85%
With phosphorus trichloride In N,N-dimethyl-formamide at -20℃; for 1h;	85%

C13H18N2S → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
Stage #1: C13H18N2S With iodine; triethylamine In tetrahydrofuran at 20℃; for 2h; Stage #2: With potassium hydroxide In ethanol for 8h; Heating / reflux;

conc. hydrogen chloride + diethyl chlorophosphate (814-49-3) + 3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl methyl ketone (88579-23-1) → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane; water; ethyl acetate
With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane; water; ethyl acetate

2,2-dibromo-1-(4,4-dimethylthiochroman-6-yl)ethylene → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane

diethyl chlorophosphate (814-49-3) + 3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl methyl ketone (88579-23-1) → (4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1)

Conditions	Yield
With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane
With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 4-iodo-3-nitrobenzoate (57362-77-3) → ethyl 3-nitro-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 70℃; for 8h; Inert atmosphere;	97%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 2-chloro-4-iodobenzoate → ethyl 2-chloro-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 80℃; for 8h; Inert atmosphere;	95%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 2-(4-bromophenyl)-1H-benzimidazole (2622-74-4) → C26H22N2S (1038865-98-3)

Conditions	Yield
With copper(l) iodide; triethylamine; triphenylphosphine; palladium dichloride In dimethyl sulfoxide at 90℃; Sonogashira coupling;	90%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 2-fluoro-4-iodobenzoate (205750-82-9) → ethyl 2-fluoro-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 80℃; for 6h; Inert atmosphere;	86%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 2-amino-4-iodobenzoic acid (20776-54-9) → 2-amino-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoic acid

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 75℃; for 12h; Inert atmosphere;	85%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + triethyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)silane (745783-97-5) → (Z)-(2-(4,4-dimethylthiochroman-6-yl)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)triethylsilane

Conditions	Yield
With potassium hexamethylsilazane at 70℃; for 12h; stereoselective reaction;	84%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 2,3-difluoro-4-iodobenzoate → ethyl 2,3-difluoro-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 75℃; for 8h; Inert atmosphere;	82%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 4-iodo-2-methoxybenzoic acid-methyl ester (148490-97-5) → C22H22O3S

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; isopropylamine In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;	82%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 2-hydroxy-4-iodobenzoate (730977-57-8) → ethyl 4-((4,4-dimethylthiochroman-6-yl)ethynyl)-2-hydroxybenzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; isopropylamine In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;	82%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 6-chloro-3-pyridinecarboxylic acid ethyl ester (49608-01-7) → 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl] nicotinic acid ethyl ester hydrochloride

Conditions	Yield
Stage #1: (4,4-dimethylthiochroman-6-yl)acetylene; 6-chloro-3-pyridinecarboxylic acid ethyl ester With copper(l) iodide; triethanolamine; bis-triphenylphosphine-palladium(II) chloride In dimethyl sulfoxide at 20 - 98℃; for 3h; Stage #2: With hydrogenchloride In ethyl acetate at 20℃; for 2.25h;	81%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + methyl 4-iodosalicylate (18179-39-0) → methyl 4-((4,4-dimethylthiochroman-6-yl)ethynyl)-2-hydroxybenzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; isopropylamine In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;	81%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + C10H11IO3 → C23H24O3S

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; isopropylamine In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;	77%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + methyl 3-acetamido-4-iodobenzoate (51411-83-7) → methyl 3-acetamido-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 70℃; for 8h; Inert atmosphere;	76%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + N,N-dimethyl-aniline (121-69-7) → N-(3-(4,4-dimethylthiochroman-6-yl)prop-2-yn-1-yl)-N-methylaniline

Conditions	Yield
With tert.-butylhydroperoxide; copper(I) bromide In decane at 100℃; for 3.25h; Inert atmosphere;	76%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + methyl 4-iodo-3-methoxybenzoate (35387-92-9) → C22H22O3S

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; isopropylamine In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;	75%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + (3-bromo-3, 3-difluoroprop-1-yn-1-yl)triisopropylsilane (257887-58-4) → C25H34F2SSi

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; caesium carbonate; tris-(o-tolyl)phosphine In toluene at 100℃; for 24h;	74%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 2-chloropyrimidine-5-carboxylate (89793-12-4) → ethyl 2-((4,4-dimethylthiochroman-6-yl)ethynyl)pyrimidin-5-carboxylate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 75℃; for 22h; Inert atmosphere;	73%
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide for 22h; Inert atmosphere;	73%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) → 4,4-dimethyl-6-ethynylthiochromane S-oxide (864841-55-4)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 3h;	72%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + trifluoroacetaldehyde N-triftosylhydrazone → 5-(4,4-dimethylthiochroman-6-yl)-3-(trifluoromethyl)-1H-pyrazole

Conditions	Yield
With potassium hydroxide In 1,4-dioxane at 100℃; for 10h; Schlenk technique; Glovebox; Inert atmosphere;	72%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 5-bromopyrazine-2-carboxylate (36070-83-4) → ethyl 5-((4,4-dimethylthiochroman-6-yl)ethynyl)pyrazin-2-carboxylate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 80℃; for 8h; Inert atmosphere;	71.5%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + methyl 3-hydroxy-4-iodobenzoate (157942-12-6) → methyl 4-((4,4-dimethylthiochroman-6-yl)ethynyl)-3-hydroxybenzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; isopropylamine In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;	71%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + ethyl 3-fluoro-4-iodobenzoate (1027513-43-4) → ethyl 3-fluoro-4-((4,4-dimethylthiochroman-6-yl)ethynyl)benzoate

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 70℃; for 8h; Inert atmosphere;	68%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 5-chloropyrimidine-2-carbonitrile (38275-56-8) → 2-cyano-5-((4,4-dimethylthiochroman-6-yl)ethynyl)pyrimidine

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine In N,N-dimethyl-formamide at 50℃; for 22h; Inert atmosphere;	65%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 6-chloro-3-pyridinecarboxylic acid ethyl ester (49608-01-7) → tazarotene (118292-40-3)

Conditions	Yield
Stage #1: 6-chloro-3-pyridinecarboxylic acid ethyl ester With potassium carbonate; triphenylphosphine; 5%-palladium/activated carbon In toluene at 45 - 50℃; Stage #2: (4,4-dimethylthiochroman-6-yl)acetylene; copper(l) iodide In toluene at 45 - 115℃; Product distribution / selectivity;	60%
Stage #1: 6-chloro-3-pyridinecarboxylic acid ethyl ester With palladium on activated charcoal; potassium carbonate; sodium sulfate; triphenylphosphine In toluene at 50 - 55℃; for 2h; Sonogashira Cross-Coupling; Inert atmosphere; Stage #2: (4,4-dimethylthiochroman-6-yl)acetylene With copper(l) iodide In toluene at 105 - 115℃;	9 g

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) + 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (88284-48-4) → 6-((2-iodophenyl)ethynyl)-4,4-dimethylthiochromane

Conditions	Yield
With N-iodo-succinimide; chloro[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]copper(I); caesium carbonate; cesium fluoride In acetonitrile at 60℃; for 12h; Schlenk technique; Inert atmosphere; Sealed tube;	54%

(4,4-dimethylthiochroman-6-yl)acetylene (118292-06-1) → tazarotene (118292-40-3)

Conditions	Yield
With copper(l) iodide; potassium carbonate; tetrakis(triphenylphosphine) palladium(0); triphenylphosphine In tetrahydrofuran for 5h; Product distribution / selectivity; Heating / reflux;
With copper(l) iodide; triethylamine; bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine In tetrahydrofuran at 25 - 30℃; for 24h; Product distribution / selectivity;

Upstream product

• 864841-55-4 4,4-dimethyl-6-ethynylthiochromane S-oxide 
• 814-49-3 diethyl chlorophosphate 
• 88579-23-1 3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl methyl ketone 
• 1187617-88-4 6-(1,1-dichloroethyl)-4,4-dimethylthiochroman 

Downstream Products

• 118292-40-3 tazarotene 
• 120236-90-0 ethyl 4-[4,4-dimethylthiochroman-6-ylethynyl]benzoate 
• 2131803-90-0 ethyl 2-((4,4-dimethyl-1-oxothiochroman-6-yl)ethynyl)pyrimidin-5-carboxylate 
• 2131803-93-3 2-((4,4-dimethyl-1-oxothiochroman-6-yl)ethynyl)pyrimidin-5-carboxylic acid 

Relevant articles and documents

PROCESS FOR PREPARATION OF TAZAROTENE

Disclosed herein is process for preparation of 6-[2-(4,4-dimethylthiochroman-6- yl)ethynyl]nicotinate known as Tazarotene of Formula (I) and its pharmaceutical acceptable salts, wherein said process comprises, reacting 4,4-dimethyl-6- acetylthiochroman with chlorinating reagent to get novel intermediate compound 6- (l,l-dichloroethyl)-4,4-dimethylthiochroman followed by converting the compound 6- (l,l-dichloroethyl)-4,4-dimethylthiochroman to get Tazarotene.

Process for the preparation of Tazarotene

Tazarotene is prepared by deoxygenation of the corresponding S-oxide, in turn obtained according to two alternative synthetic pathways.

PROCESS FOR THE PREPARATION OF ACETYLENIC RETINOID

A process for the preparation of acetylenic retinoid, ethyl-6-[2- (4,4- dimethylthiochroman-6-yl)ethynyl]nicotinate, a compound of formula 1,comprising, (a) cyclizing phenyl-3-methylbut-2-enylsulfide, a compound of formula 6, in presence of an acid selected from sulfuric acid or p-toluenesulfonic acid to yield 4,4-dimethylthiochroman, a compound of formula 2; (b)acetylating the compound of formula 2, to 4,4 -dimethyl-6-acetylthiochroman, a compound of formula 3; (c)(i) reacting the compound of formula 3 with hydrazine;(ii) reacting resultant product of step (i) with iodine; (iii) converting the resultant product of step (ii) to 4,4-dimethyl-6- ethynyl thiochroman, a compound of formula 4 and (d) reacting the compound of formula 4 with ethyl-6-halonicotinate, a compound of formula 5, wherein X is Cl or Br, in presence of cuprous halide, a transition metal and an inorganic base.