6-Methoxy-2-naphthaldehyde

ANALYTICAL METHOD

Appearance of solution (5% methylene chloride)
Prepare a 5% solution (w/v) of the product in methylene chloride. The solution should appear clear.

Water content
In a titration vessel transfer 35 to 40 ml of pyridine and about 200mg , accurately measured, of sample. Determine the content of water by Karl Fisher titrimetric method as directed in USP23, <921>, p.1840 method 1a.

Chromatographic purity (TLC)
Operating conditions:
Chromatographic plate silica gel 60F 254, 0.25mm, Merck, 10 x 20 cm
Application volume 2 m l
Mobile phase - Cyclohexane 75ml
- ethyl acetate 25ml
Detection UV 254 nm and 366 nm
Saturation time of the chamber 30 minutes

Sample solution
Accurately weigh, 500mg of the sample in a 10 ml volumetric flask. Dissolve and dilute to volume with CH2Cl2.

WSTD solution
Accurately weigh, 500mg of the working standard in a 10ml volumetric flask. Dissolve and dilute to volume with CH2Cl2

Impurity reference solutions
•  Accurately weigh, 100mg of 6,6'dimethoxy-2,2'-binaphthyl in a 100ml volumetric flask. Dissolve and dilute to volume with CH₂Cl₂. Pipet accurately 1ml of the above solution and transfer in a 10 ml volumetric flask. Dilute to volume with CH₂Cl₂.
•  Accurately weigh, 100mg of 6-methoxy-2-naphtoic acid in a 100 ml volumetric flask. Dissolve and dilute to volume with CH₂Cl₂. Pipet accurately 1 ml of the above solution and transfer in a 10 ml volumetric flask. Dilute to volume with CH₂Cl₂.
•  Accurately weigh 50mg of 6-methoxy-2-naptyl alcohol in a 100 ml volumetric flask. Dissolve and dilute to volume with CH₂Cl₂ [Sol. C]

Procedure
Apply 2 m l of sample and WSTD solutions.
Further apply impurity reference solutions as tabulated below:

Allowed the spots to dry, and develop the chromatogram in the mobile phase. Freshly prepared using a paper lined equilibrated tank, until the solvent front has moved about 14cm of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, allow to air dry, and examine the plate under short-wavelength ultraviolet light (254 and 366 nm).

6,6'-dimethoxy-2,2'-binaphthyl impurity : a secondary spot present on the sample run at RF of 6,6'-dimethoxy-2,2'-binaphthyl impurity should be not more intense than the spot obtained with ¡°reference solution 1¡±

6-methoxy-2-naptoic acid impurity : a secondary spot present on the sample run at RF of 6-methoxy-2-naphtoic acid impurity should be not more intense than the spot obtained with ¡°reference solution 2¡±.

6-methoxy-2-naphtyl alcohol impurity : a secondary spot present on the sample run at RF of the 6-methoxy-2-naphtyl alcohol impurity should be not more intense than the spot obtained with ¡°reference solution 3¡±

Fluorescent impurity : Compare the intensity of fluorescent impurity of the sample run, if present, to the intensity of the spot at RF of about 0.39 obtained with the chromatogram of the WSTD solution.

Chromatographic purity and impurities (GC)

Operating conditions:
Gas chromatograph : Shimadzu 17A with autosampler (or equivalent)
Column : type: DB-1, J&W
Length : 60 m
i.d. : 0.53 nm
film thickness : 1.5 m m (or equivalent)
Detector : FID
Detector temperature : 275 °C
Injector temperature : 250 °C
Injection volume : 0.4 m l
Carrier : He
Oven temperature T oven 1: 180 °C
Iso time 1: 0 min
Ramp rate 1: 1 °C/min
T oven 2: 210 °C
Iso time 2: 2.0 min

Sample solution
Prepare a solution of the sample having a concentration of 2% in methylene (chloride)

Procedure
Inject 0.4 m l of sample solution. Record the chromatogram.

Calculations:
Calculate the area percent of the product and impurities by the following formula:

where:
Ax = peak area corresponding to ¡°x¡± peak in the chromatogram
Ai = peak area corresponding to ¡°i¡± peak in the chromatogram
i = total number of peaks in the chromatogram

Reducing Substances:
Product :6-methoxy-2-naphthaldehyde
Reagents : KmnO, N/10, distilled water (reducing substances-free)
Sample preparation : weigh 5gm of sample and reslurry with 50ml of distilled water for 1 hour at room temperature. Filter the suspension and transfer 10ml of the filtered solution into a Nessler comparison tube. Add 5 drops of KmnO4 N/10. Keep the sample solution in a dark place for 30 minutes

Standard preparation : weigh 5gm of WSTD and reslurry with 50 ml of distilled water for 1 hour at room temperature. Filter the suspension and transfer 10 ml of the filtered solution into a Nessler comparison tube. Add 5 drops of KmnO4 N/10. Keep the standard solution in a dark place for 30 minutes.

Evaluation : observe the sample and standard solutions over a white surface. The sample solution should appear pink colored as the standard solution. If reducing substances are present in the sample, the solution color turns yellow to slightly pink.