I am using thiophosgene to convert primary aromatic amine to isothiocyanate in a biphasic solvent system (chloroform/water). Under these conditions tert-butyl ester in my starting material is cleaved. I am looking for a milder route to do this conversion that will retain the ester.
You can be isothiocyanate by adding Amines to a solution of methanol containing triethylamine and carbon disulphide at 0 C to form dithiocarbamate salt, dithiocarbanmate salt will precipitate out, just filtered and dried and this dithiocarbamate salt further be treated with triphosgene and chloroform at 0C to obtain isothiocyanate
"A general and facile one-pot protocol for the preparation of a broad range of alkyl and aryl isothiocyanates..." : Beilstein J. Org. Chem. 2012, 8, pp. 61–70.
doi:10.3762/bjoc.8.6
https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-8-6.pdf
Reaction of primary amine with CS2 in pyridine in the presence of DCC
Angew Chem 79 151 1967
Reaction of amines with 1,1′-thiocarbonyldi-2(1H)-pyridone in dichloromethane (usualy 30 min reaction is compleated)
Kim, S.; Yi, K. Y. J. Org. Chem. 1986, 51, 2613−2615.
1) Thiophosgene (1 equivalent) is added to a stirred two phase mixture of aromatic Amine (1 equivalent) in CHCl3 and saturated solution of NaHCO3 at 0°C. The mixture is then stirred at RT.
2) We often prepared larger amounts of isothiocyanates (~ 10-50 kg) by addition of thiophosgene (1.3 eq) to aromatic amines (1.0 eq) in toluene in the presence of a catalytic amount of dimethylformamide. (Temperature: 20°C until reflux). In some cases, the HCl was trapped with NEt3.
Thanks Bruno for your reply. Do you have any reference for trapping HCl with NEt3 ? it will be very helpful for me
Dear Moustafa,
Several years ago we prepared an aromatic isothiocyanate by addition of thiophoshene (1.2 eq) to a mixture of amine (1.0 eq) and 2.4 eq of NEt3 in CHCl3 at 0°C. Then the reaction mixture was stirred for several hours at RT before it was quenched with water. (Yield: 78-82%).
Merck (W02013/124026 A1, 2013) and Nippon Kayaku as well as others carried out similar reactions with Hünig Base or NEt3 and CH2Cl2 or THF as solvent at 0°C.
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