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17th March 2011 @ 07:14
Acid-catalyzed Pictet-Spengler using methanesulfonic acid in various concentrations

Continuation of Acid-catalyzed Pictet-Spengler reaction with methanesulfonic acid (MW56-5 to MW56-8)

reaction scheme MW56-9 to MW56-14


reaction scheme MW56-9 to MW56-14


See also:
Acid-catalyzed Pictet-Spengler reaction with binaphthalenedisulfonic acid (MW56-1 to MW56-4)

Hazard and Risk Assessment:
HRAF MW56.pdf


Start time: 6:30 pm 17/03/2011
End time: 9:30 am 18/03/2011

MW56-9:
A solution of MW29-4 (18.8 mg, 50.0 µmol, M.W. 376.5 g/mol) and methanesulfonic acid (4.8 mg, 50.0 µmol, 3.25µL, 1 eq., M.W. 96.1 g/mol) in toluene (1 mL) was stirred for 15 h at 70°C.
Data: LCMS MW56-9 (16h).pdf: unspecific signals, no starting material or product
[M.W.(PZQ) = 312 g/mol]

MW56-10:
MW29-4 (18.8 mg, 50.0 µmol, M.W. 376.5 g/mol) was dissoved in a solution of toluene (0.9 mL) and methanesulfonic acid (0.1 mL) and was stirred for 15 h at 70°C.
Data: LCMS MW56-10 (16h).pdf: PZQ (RT = 13.3 min) + unknown side product (RT = 12.9 min, m/z = 339)

MW56-11:
MW29-4 (18.8 mg, 50.0 µmol, M.W. 376.5 g/mol) was dissoved in a solution of chloroform (0.9 mL) and methanesulfonic acid (0.1 mL) and was stirred for 15 h at 65°C.
Data: LCMS MW56-11 (16h).pdf: unknown main product (RT = 12.9 min, m/z = 339), see MW56-10, PZQ (RT = 13.3 min)

MW56-12:
A solution of MW51-1 (18.5 mg, 50.0 µmol, M.W. 370.4 g/mol) and methanesulfonic acid (4.8 mg, 50.0 µmol, 3.25µL, 1 eq., M.W. 96.1 g/mol) in toluene (1 mL) was stirred for 15 h at 70°C.
Data: LCMS MW56-12 (16h).pdf: N-benzyl-PZQ (RT = 12.4 min), no side products visible
[M.W.(N-benzyl-PZQ) = 306 g/mol]


MW56-13:
MW51-1 (18.5 mg, 50.0 µmol, M.W. 370.4 g/mol) was dissoved in a solution of toluene (0.9 mL) and methanesulfonic acid (0.1 mL) and was stirred for 15 h at 70°C.
Data: LCMS MW56-13 (16h).pdf: N-benzyl-PZQ (RT = 12.4 min), no side products

MW56-14:
MW51-1 (18.5 mg, 50.0 µmol, M.W. 370.4 g/mol) was dissoved in a solution of chloroform (0.9 mL) and methanesulfonic acid (0.1 mL) and was stirred for 15 h at 65°C.
Data: LCMS MW56-14 (16h).pdf: N-benzyl-PZQ (RT = 12.3 min), no side products


Work-up:
- neutralized with sat. Na2CO3 solution, extracted with ethyl acetate, dried over Na2SO4.
- sample preparation for LCMS: 30 µL solution (c=3.3 mg/mL in ethyl acetate) was filtered through a micro column (silica gel, ethyl acetate, 100%) and evaporated. The residue (about 10 µg) was dissolved in 2.5 mL acetonitrile (c ~ 40 µg/mL).

TLC1: before work-up (ethyl acetate, 100%, stain: potassium permanganate)
TLC2: after work-up (ethyl acetate, 100%, stain: potassium permanganate)
TLC1 MW56-9 to 14.jpg
TLC2 MW56-9 to 14.JPG


* LCMS Method: HPLC: Waters sunfire C18; gradient A water, B acetonitrile + 0.1 % formic acid, 0 to 100%B over 15 min, flow 0.2 ml/min flow rate.

Results:
MW56-9 to MW56-11 (Ugi-intermediate):
Different results for different conditions; no product in MW56-9 (mistake in the procedure ??), different product/ (unknown) side product ratio for toluene and chloroform, respectively

MW56-12 to MW56-14 (N-benzoyl-intermediate):
Clean Pictet-Spengler cyclization to N-benzoyl-PQZ in all cases, no side products obtained.
Linked Posts
Attached Files
reaction scheme MW56-9 to MW56-14
TLC1 MW56-9 to 14.jpg
TLC2 MW56-9 to 14.JPG
LCMS MW56-9 (16h).pdf
LCMS MW56-13 (16h).pdf
LCMS MW56-14 (16h).pdf
LCMS MW56-10 (16h).pdf
LCMS MW56-11 (16h).pdf
LCMS MW56-12 (16h).pdf