IDENTIFIABLE CHEMICAL PRODUCT

Abstract

The invention is a process for manufacturing a chemical product which may be later identified and distinguished from similar chemical products, and comprises the steps of (i) forming a reaction mixture comprising chemical intermediate A, chemical intermediate B and marker chemical M (ii) providing the conditions which enable chemical intermediate A and chemical intermediate B to react together to form chemical product C, and for marker chemical M to react either with chemical intermediate A to form a marker product AM or with chemical product C to form a marker product CM (iii) after said reactions have taken place, separating a mixture of product C with product AM and/or a mixture of product C with marker product CM from the reaction mix tune wherein product AM and product CM are both distinguishable from product C by analysis. By using the method of the invention, the marked product is formed in situ and in a mixture with unmarked product.

Claims

1. A process for manufacturing a chemical product which may be identified and distinguished from similar chemical products, the process comprising the steps of: forming a reaction mixture comprising chemical intermediate A, chemical intermediate B and marker chemical M; (ii) providing the conditions which enable chemical intermediate A and chemical intermediate B to react together to form chemical product C, and for marker chemical M to react either with chemical intermediate A to form a marker product AM or with chemical product C to form a marker product C; and (iii) after said reactions have taken place, separating a mixture of chemical product C with marker product AM and/or a mixture of chemical product C with marker product CM from the reaction mixture, wherein marker product AM and marker product CM are both distinguishable from chemical product C by analysis of said mixture.

2. The process of claim 1, wherein chemical intermediate B incorporates a functional group capable of reacting with chemical intermediate A and marker chemical M incorporates the same type of functional group.

3. The process of claim 1, wherein chemical intermediate B incorporates a functional group capable of reacting with chemical intermediate A and marker chemical M incorporates a different type of functional group capable of reacting with chemical intermediate A or chemical product C.

4. The process of claim 1, wherein the mixture of chemical product C with marker product AM or CM separated from the reaction mixture in step (iii) is a homogeneous mixture.

5. The process of claim 1, wherein the relative amounts of said marker product CM or marker product AM and chemical product C in said mixture may be determined by said analysis.

6. The process of claim 1, wherein said analysis comprises at least one analytical method selected from spectroscopy and chromatography.

7. The process of claim 6, wherein said analytical method is selected from the group consisting of spectrophotometric absorption in the ultraviolet, visible, near infrared or mid-infrared regions; fluorescent emission spectroscopy; nuclear magnetic resonance spectroscopy, electron spin resonance spectroscopy, Raman spectroscopy, resonance Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS); surface-enhanced resonance Raman spectroscopy (SERRS), tip enhanced Raman spectroscopy, spatially off-set Raman spectroscopy, gas chromatography, liquid chromatography or HPLC.

8. The process of claim 1, wherein chemical product C is a herbicide, a pesticide, an active pharmaceutical ingredient (API), a food ingredient, a dye, a pigment, an aroma compound, a fuel additive, a polymer or a plant product.

9. The process of claim 1, wherein chemical product C comprises an ingredient in a composition.

10. The process of claim 1, wherein said mixture contains from 1 ppb by weight to 1% by weight of marker product AM or marker product CM based on the total weight of chemical product C and said marker product.

11. The process of claim 1, wherein at least two marker chemicals M1, M2 . . . Mn are present in said reaction mixture, wherein n represents the number of marker chemicals M present in the mixture, each said marker chemical M forming a different marker product and each said different marker product being distinguishable from chemical product C and from each other marker product present in the mixture by analysis.

12. The process of claim 11, wherein the relative proportions of marker chemicals M1-Mn are calculated to provide an identifiable signal ratio of each marker product when said mixture is analysed.

13. A composition, comprising an intimate mixture of: (a) a chemical product C; and (b) a marker product AM, wherein marker product AM is formed by reaction of a chemical intermediate A with a marker chemical M and chemical compound C is formed by reaction of chemical intermediate A with a chemical intermediate B.

14. A composition comprising an intimate mixture of: (a) a chemical product C; and (b) a marker product CM, wherein marker product CM is formed by reaction of a marker chemical M with chemical compound C.

15. The composition of claim 13, wherein chemical product C is formed in the same reaction mixture as marker product CM or marker product AM.

16. The composition of claim 13, further comprising an additional marker compound.

17. The composition of claim 14, wherein chemical product C is formed in the same reaction mixture as marker product CM or marker product AM.

18. The composition of claim 14, further comprising an additional marker compound.

Description

EXAMPLE 1

Synthesis of Marked DEET

[0038] Diethylamine (0.248 g, 3.40 mmol) and 3-ethynyl-phenylamine (0.4 mg, 0.0032 mmol) (from stock solution in CHCl.sub.3) were added to a solution of m-toluoyl chloride (0.50 g, 3.23 mmol) in CHCl.sub.3 (5 ml). Triethylamine (TEA) (0.86 ml, 4.85 mmol) was added and the mixture stirred at room temperature for 2 hours. The reaction was quenched with water (5 ml), diluted with dichloromethane (10 ml) and the organic phase was separated and washed with HCl (15%, 10 ml) then brine (5 ml). The organic phase was dried (MgSO.sub.4) and concentrated in vacuo to afford DEET (0.58 g, 3.03 mmol, 94%) tagged at 0.1 mol % as a colourless oil.

##STR00001##

[0039] An untagged DEET compound was made by the same method but omitting the 3-ethynyl-phenylamine from the reaction mixture. The product was confirmed by GC-Mass spectroscopy and NMR spectroscopy.

[0040] The SERS response was detected by the following method. 10 mg of either untagged DEET or the tagged DEET mixture prepared in Example 1 was taken up in water (2 ml) and shaken to form a stock solution. Gold colloid (500 L, 60.7 nm in citrate buffer, 0.01% w/w supplied by Cabot) and deionised water (300 L) were added to 100 L of the above stock solution and the mixture shaken. NaCl (100 L, 5% aq.) was added, the mixture shaken and the SERS response of the resulting solution was then collected using an Ocean Optics 785 nm laser (QE65000, 1000 ms integration, 5 iterations). The SERS spectra are shown in FIG. 1. Untagged DEET shows a weak SERS band at 995 cm-1. Distinct SERS bands can be seen in the tagged samples at 1161, 1252, 1303 and 1595 cm-1 (in addition to a signal at 995 cm-1). The tagged DEET product mixture is therefore readily detectable using SERS and may be identified as a compound made using the method of the invention.

EXAMPLE 2

Synthesis of Marked Lidocaine

[0041] ##STR00002##

[0042] Potassium iodide (0.18 g, 1.07 mmol) was added to a solution of 2-chloro-N-(2,6-dimethyl-phenyl)-acetamide (0.212 g, 1.07 mmol), diethylamine (0.10 ml, 0.97 mmol) and 3-ethynyl-phenylamine (0.126 mg, 0.0011 mmol) in dimethylformamide (1 ml) and toluene (10 ml) and the mixture stirred at reflux for 2 h. Water (20 ml) was added and the organic phase was extracted and washed with water (20 ml) then dried over MgSO.sub.4. Concentration in vacuo produced a mixture of lidocaine and tagged lidocaine (0.1 mol %) as a white crystalline solid (0.179 mg, 0.76 mmol, 79%).

[0043] An un-tagged lidocaine product was made by the following method: Diethylamine (0.39 ml, 3.74 mmol) was added to a solution of 2-chloro-N-(2,6-dimethyl-phenyl)-acetamide (0.25 g, 1.25 mmol) in toluene (10 ml) and the mixture stirred at reflux for 3 h. After cooling to room temperature the reaction was quenched with aq. HCl (10%, 10 ml). The aqueous phase was collected and basified with aq. NaOH until strongly basic. Ethyl acetate (20 ml) was added and the organic layer removed, dried over MgSO.sub.4 and concentrated in vacuo. Recrystallisation from n-pentane afforded lidocaine (0.11 g, 0.47 mmol, 38%) as white, needle-like, crystals. The product was confirmed by GC-MS and NMR.

[0044] Both 0.1 mol % marked and unmarked Lidocaine (30 mg) were separately taken up in water (3 ml) and acetone (0.1 ml) and shaken to form a stock solution. Gold colloid (500 L, 60.7 nm in citrate buffer, 0.01% w/w supplied by Cabot) and deionised water (300 L) were added to 100 L of the above stock solution and the shaken. NaCl (100 L, 5% aq.) was added, the mixture shaken and the SERS response of the resulting solution was then collected using an Ocean Optics 785 nm laser (QE65000, 1000 ms integration, 5 iterations). The spectra are shown in FIG. 2. Distinct SERS bands can be seen in the tagged sample at 1157, 1574 and 1590 cm-1.