Primaquine diphosphate

Phosphate Primaquine phosphate, Primaquine (diphosphate de), Primaquini diphosphas, Primaquinbisdihydrogenphosphat, Primaquine diphosphate, Difosfato de Primaquina, Primachina Fosfato, Primaquinum Phosphoricum SN-13272 [1-6],... 

Primaquine diphosphate orange-red or orange crystalline powder, odorless and has bitter taste, solution is acid to litmus. 

Bromo-l-phthalimidopentane 3 was obtained in 72-82 g yield by refluxing 92 g of 1,4-dibromopentane 1, 55.5 g of potassium phthalimide 2, and 200 mL dry acetone on a steam bath for 30 h. Compound 3 (30 g) and 42 g 6-methoxy-8-aminoquinoline 4 refluxed at 130-135 °C for 6 h, extracted with benzene to separate insoluble 6-methoxy-8-aminoquinoline hydrobromide, the residue from evaporation of the benzene was refluxed with stirring with 100 mL of an alcoholic solution of 6 g hydrazine hydrate for 4 h, the solution was concentrated, made acidic to Congo red with 8 N hydrochloric acid, filtered, and washed with boiling water. The combined filtrate and washings was concentrated, made alkaline, extracted with benzene, and distilled in vacuo to give 20.5 g primaquine 6, which was treated with 19 mL 85% phosphoric acid in absolute ethanol, formed 42.5% primaquine diphosphate. 

Primaquine diphosphate Soluble 1 in 16 of water, practically insoluble in ethanol, chloroform, and ether. 

Primaquine diphosphate melts at about 197—198 °C and primaquine oxalate melts at 182.5—185 °C. Primaquine as a base is viscous liquid that boils at 175—179°C. Primaquine oxalate m.p. 182.5—185 °C. 

The differential scanning calorimetry (DSC) thermogram of primaquine diphosphate was obtained using a DuPont TA-9900 thermal analyzer attached to a DuPont Data unit. The thermogram shown in Fig. 2 was obtained at a heating rate of 10 °C/min, and was run from 50 to 300 °C. The compound was found to melt at 209.8 °C. 

The infrared (IR) absorption spectrum of primaquine diphosphate was obtained as KBr disc using a Perkin-Elmer infrared spectrometer. The infrared spectrum is shown in Fig. 4 and the principal peaks are at 2946, 1612, 1469, 1430, 1384, 1200, 1050, 956, 815, and 760 cm-1. The assignments of the infrared absorption bands of primaquine diphosphate are shown in Table 2. Clarke reported the following principal peaks at 1611, 1595, 815, 1230, 1572, and 1170 cm-1 (KBr disk) [2],... 

The proton nuclear magnetic resonance (NMR) spectra of primaquine diphosphate was obtained using a Bruker instrument operating at 300, 400, or 500 MHz. 

Table 1. Crystallographic data from the X-ray powder diffraction pattern of primaquine diphosphate...

Standard Bruker Software was used to execute the recording of DEPT, COSY, and HETCOR spectra. The sample was dissolved in DMSO-d6 and all resonance bands were referenced to tetramethylsilane (TMS) internal standard. The H NMR spectra of primaquine diphosphate are shown in Figs. 5-8. The H NMR assignments of primaquine diphosphate are shown in Table 3. 

The 13C NMR spectra of primaquine diphosphate were obtained using a Bruker instrument operating at 75, 100, or 125 MHz. The sample was dissolved in DMSO-d6 and tetramethylsilane (TMS) was added to function as the internal standard. The 13C NMR spectra are shown in Fig. 9. The HSQC and HMBC spectra are shown in Figs. 10 and 11, respectively. The DEPT 90 and DEPT 135 are shown in Figs. 12 and 13, respectively. The assignments for the observed resonance bands associated with the various carbons are provided in Table 4. 

Fig. 2. Differential scanning calorimetry thermogram of primaquine diphosphate.

The mass spectrum of primaquine diphosphate was obtained using a Shimadzu PQ-5000 mass spectrometer. The parent ion was collided with helium as a carrier gas. Figure 14 shows the detailed mass fragmentation pattern for primaquine diphosphate. Table 5 shows the proposed mass fragmentation pattern of the drugs. Clarke reported the following principal peaks at m/z 201, 81, 98, 175, 259, 176, 202, and 242 [2]. 

Fig. 4. The infrared absorption spectrum of primaquine diphosphate (KBr pellet).

Table 2. Vibrational assignments for primaquine diphosphate infrared absorption bands ...

Test 2 Examine by infrared absorption spectrophotometry, according to the general procedure (2.2.24), comparing with spectrum obtained with primaquine diphosphate Chemical Reference Substance (CRS). Examine the substance as discs prepared as follows dissolve separately 0.1 g of primaquine diphosphate and the reference substance in 5 mL of water R, add 2 mL of dilute ammonia R and 5 mL of chloroform R and shake dry the chloroform layer over 0.5 g of anhydrous sodium sulfate R prepare a blank disc using about 0.3 g of potassium bromide R, apply dropwise to the disc 0.1 mL of the chloroform layer, allowing the chloroform to evaporate between applications dry the disc at 50 °C for 2 min. 

Test solution Dissolve 0.2 g of primaquine diphosphate in 5 mL of water R and dilute to 10 mL with methanol R. Dilute 1 mL of the solution to 10 mL with a mixture of equal volumes of methanol R and water R. 

Reference solution Dissolve 20 mg of primaquine diphosphate CRS in 5 mL of water R and dilute to 10 mL with methanol R. 

Test 4 Dissolve 50 mg of primaquine diphosphate in 5 mL of water R. Add 2 mL of dilute sodium hydroxide solution R and shake with two quantities, each of 5 mL, of chloroform R. The aqueous layer, acidified by addition of nitric acid R, gives reaction (b) of phosphates, as described in the general procedure (2.3.1). 

Test solution Dissolve 50 mg of primaquine diphosphate in water R and dilute to 5 mL with the same solvent. To 1 mL of this solution add 0.2 mL of concentrated ammonia R and shake with 10 mL of the mobile phase. Use the clear lower layer. 

Table 3. Assignments of the resonance bands in the NMR spectrum of primaquine diphosphate...

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