13C-labeled chlorinated paraffins and their preparation

Abstract

The present invention preferably has no geminal or terminal chlorine atoms in the structure. 13 C-labeled chlorinated paraffins, their preparation methods and their uses.

Description

[Technical field]

[0001] The present invention relates to 13 This invention relates to C-labeled chlorinated paraffins and their preparation methods and uses.

[0002] All patents, publications, or other disclosure materials that are said to be incorporated by reference herein are incorporated herein only to the extent that the incorporated materials do not contradict existing definitions, descriptions, or other disclosure materials described in this disclosure. Thus, to the extent necessary, the disclosures described herein supersede any conflicting materials incorporated herein by reference. Any materials or portions thereof that are said to be incorporated by reference herein but that contradict existing definitions, descriptions, or other disclosure materials described herein are incorporated only to the extent that no contradiction occurs between the incorporated materials and the existing disclosure materials. [Background technology]

[0003] Chlorinated paraffins (CPs or CPs) are a class of industrial chemicals used as high-temperature lubricants in metalworking machines and as flame-retardant plasticizers in vinyl plastics. Less common uses include use as flame retardants in rubber, paints, adhesives, and as sealants. Technical CPs are classified as polychlorinated alkanes (PCAs) with a chlorination degree of 30%-70%, and C8-C9 (very short chain CPs, vSCCPs), C 10 ~C 13 (Short Chain CP, SCCP), C 14 ~C 17 (Medium Chain CP, MCCP) and C 18 ~C 30 Long-chain CPs (LCCPs) are complex mixtures of linear alkane chains with different lengths. The general molecular formula for CPs is C n H 2n+2-y Cl y , n=10~30.

[0004] The industrial chemicals for CP are C using molecular chlorine either in liquid paraffin or in a solvent. 10 ~C30 It is produced by the chlorination of n-alkanes. Depending on the n-alkane feedstock, the reaction occurs at temperatures between 50 and 150 °C, at high pressure and / or in the presence of UV light. Total worldwide production is largely unknown but is thought to exceed at least 2 million metric tons per year.

[0005] CPs exhibit resistance to degradation, some exhibit the potential for bioaccumulation and toxicity, and are suspected to be carcinogenic to humans. SCCPs have been banned by the EU POPs legislation since 2017 and are on several watch lists, such as the EU Water Framework Directive.

[0006] CPs need to be continuously monitored in the environment as well as in food and feed matrices. CPs are analyzed by GC coupled to either high- or low-resolution MS (HRMS or LRMS). HRMS, two-dimensional GC (GCxGC), or LC-HRMS (APC-QTOF-HRMS) are state-of-the-art techniques to differentiate SCCPs, MCCPs, and LCCPSs.

[0007] One of the main challenges in the analysis or determination of CPs is the lack of suitable standards and matrix reference materials. So far, there are no suitable and generally accepted reference standards commercially available. Summary of the Invention [Problem to be solved by the invention]

[0008] The object of the present invention is to 13 The aim of the present invention was to provide C-labelled chlorinated paraffins. These should preferably be usable in the analysis or determination of CPs, particularly as internal standards.

[0009] A further object of the present invention is to provide such 13 Objective To provide a novel method / process for the preparation of C-labeled chlorinated paraffins.

[0010] Further, the object of the present invention is to provide a novel13 C-labeled chlorinated paraffins and those prepared by the method / process of the present invention 13 The aim of this study was to provide a method for the preparation of C-labeled chlorinated paraffins.

[0011] Further objects will become apparent to those skilled in the art upon review of the following disclosure. [Means for solving the problem]

[0012] These and other objects are solved by what is outlined in the attached independent claims.

[0013] Preferred embodiments are outlined in the dependent claims and the following description. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] It is understood that the invention is not limited to the embodiments disclosed in this Summary or the following description, but is intended to cover modifications that are within the spirit and scope of the invention as defined by the claims.

[0015] In this application, including the claims, except where indicated in the examples or otherwise, all numbers expressing quantities or properties should be understood in all instances to be modified by the term "about". Thus, unless indicated to the contrary, any numerical parameters set forth in the following description may vary depending on the desired properties sought to be obtained in the compositions and methods according to the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter set forth herein should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0016] It should also be understood that any numerical range recited herein is intended to include all subranges subsumed therein. For example, a range of "1 to 10" is intended to include all subranges between (and including) the recited minimum of 1 and the recited maximum of 10, i.e., having a minimum of 1 or more and a maximum of 10 or less. As used herein, the terms "one," "a," or "an" are intended to include "at least one" or "one or more," unless otherwise specified.

[0017] In the present invention, unless otherwise specified, the reaction is carried out at room temperature, which is understood to be 20°C.

[0018] In the present invention, unless otherwise specified, reactions are carried out at ambient pressure, which is understood to be 101.325 kPa.

[0019] In the present invention, the term "fatty acid" is used in the IUPAC Gold Book as "aliphatic monocarboxylic acids derived from or contained in esterified form in animal or vegetable fats, oils or waxes." Natural fatty acids generally have 4-28 carbon chains (usually unbranched and even-numbered), which may be saturated or unsaturated.

[0020] In a first embodiment, the present invention is 13 This invention relates to a method for preparing C-labeled chlorinated paraffins.

[0021] In principle, this method allows any 13 C-labeled chlorinated paraffins can be prepared, but in the present invention, this method does not have geminal or terminal chlorine atoms in the structure. 13 It is preferred for preparing C-labeled chlorinated paraffins.

[0022] This method of the present invention comprises: V) providing an alkene, The main chain has one or more α,β-ethylenically unsaturated double bonds, One or more carbon atoms in the main chain 13 It is substituted with a C atom, may have one chlorine atom or an odd number of chlorine atoms in the backbone, provided that there are no geminal or terminal chlorines on atoms that are part of an α,β-ethylenically unsaturated double bond; Providing an alkene or a mixture of such alkenes; VI) reacting the alkene or mixture of alkenes with a trichloride, tribromide or triiodide, preferably a trichloride, more preferably a tetraalkylammonium trichloride, even more preferably tetraethylammonium trichloride; It comprises or consists of:

[0023] In some preferred embodiments, the method also includes the further step of: Ia) At least one, more than two, or all of the carbon atoms in the main chain 13 Providing an alkanol substituted at a C atom, IIa) converting the alkanol to the corresponding bromide; IIIa) converting the bromide to a Wittig salt; IVa1) coupling a Wittig salt with an aldehyde to form an alkene having at least one α,β-ethylenically unsaturated double bond in the main chain, wherein the aldehyde is substituted at one, more than one, or all of the carbon atoms in the main chain. 13 step, optionally substituted with a C atom; or IVa2) coupling the Wittig salt with a dialdehyde to form an alkene having at least two α,β-ethylenically unsaturated double bonds in the main chain, wherein the dialdehyde is an alkene having one, more than one, or all of the carbon atoms in the main chain 13 step, optionally substituted with a C atom; Contains or Ib) At least one, more than two, or all of the carbon atoms in the main chain 13Providing an alkanol or alkenol, in particular an alkenol, substituted at a C atom, IIb) converting an alkanol or alkenol, in particular an alkenol, into the corresponding halide, in particular a bromide, IIIb) converting the halide into a Grignard reagent; IVb1) coupling of the Grignard with a tosylate species, in particular made from an alcohol, via a carbon-carbon cross-coupling reaction catalyzed by a copper, nickel or palladium complex, in particular Li2CuCl4, to form an alkene having at least one α,β-ethylenically unsaturated double bond in the backbone, wherein the alcohol species has one, more than one or all of the carbon atoms in the backbone 13 step, optionally substituted with a C atom; or IVb2) coupling the Grignard with a divalent tosylate species made from a diol via a carbon-carbon cross-coupling reaction to form an alkene having at least two α,β-ethylenically unsaturated double bonds in the backbone, wherein the diol species has one, more than one, or all of the carbon atoms in the backbone 13 Optionally substituted with a C atom, step Includes.

[0024] In some other preferred embodiments of the process according to the invention, the alkene used is a linear alkene or each of the alkenes is a linear alkene.

[0025] In one preferred variant of the invention, in particular those having an even number of chlorine atoms 13 To prepare C-labeled chlorinated paraffins, the method of the invention follows scheme 1a) or 1b), respectively (schemes 1a) and 1b) also include the synthesis of aldehyde (4) in scheme 1b). 13 C-labeled carbon atom): 1a) [ka] 1b) [ka]

[0026] In another preferred variant of the invention, in particular those having an even number of chlorine atoms 13 To prepare C-labeled chlorinated paraffins, the method of the invention follows Scheme 2a) or 2b), respectively (Scheme 2a) and 2b) also include the reaction of aldehyde (6) in Scheme 2b). 13 C-labeled carbon atom): 2a) [ka] 2b) [ka]

[0027] In yet another preferred variant of the invention, the chlorine atom is preferably a chlorine atom having an even number of chlorine atoms. 13 To prepare C-labeled chlorinated paraffins, the method of the present invention follows Scheme 3: [ka]

[0028] In yet another preferred variant of the invention, the chlorine atom is preferably a chlorine atom having an even number of chlorine atoms. 13 To prepare C-labeled chlorinated paraffins, the method of the present invention follows Scheme 4: [ka]

[0029] In all these variations, the variables and residues are as follows: R*= 13 C a -n-alkyl (straight chain alkyl), preferably having 0 to 4 carbon atoms, where a is 13is the number of C, which is from 1 to the number of carbon atoms in the alkyl chain, preferably 1 to 4; *= 13 C; Ph = phenyl; Et = ethyl; R 1 = 13 C b - an alkylene residue, preferably having 2 to 28 carbon atoms, where b is 13 C is the number of carbons, from 1 to the number of carbons in the alkene chain, preferably 1 to 4, and may contain one or an odd number of chlorine atoms, provided that there is no chlorine at the end of the residue and that the number of double bonds in the alkylene residue is a minimum of 1 to the number of theoretically possible cumulated double bonds, in particular 1 to 9, and that the double bonds are preferably neither cumulated nor conjugated; R 2 = 13 C b -chloro-alkyl residue, preferably having 2 to 28 carbon atoms, where b is a substituted or unsubstituted alkyl group in the alkyl residue, in particular of the formula 13 C b -C n H 2n+1-y Cl y of 13 C is the number of carbons, n is 2 to 28, and y is the number of chlorine atoms, 2 to 28 but preferably 2 to 27; R 3 = 13 C d - an alkylene residue, preferably having 0 to 26 or 1 to 26 carbon atoms, where d is the number of 13 C is the number of carbons, from 1 to the number of carbons in the alkylene chain, preferably 1 to 4, and may contain one or an odd number of chlorine atoms, provided that there are no chlorines at the end of the residue and that the number of double bonds in the alkylene residue is a minimum of 1 to the number of theoretically possible cumulated double bonds, and that the double bonds are preferably neither cumulated nor conjugated; R 4 = 13 C d-chloro-alkyl residue, preferably having 0 to 26 or 1 to 26 carbon atoms, where d is a chloro-alkyl residue in the alkyl residue, in particular of the formula 13 C d -C n H 2n-y Cl y of 13 C is the number of carbons, n being 0 to 26, and y is the number of chlorine atoms, being 0 to 26 but preferably 1 to 25; R 5 = 13 C e - an alkylene residue, preferably having 0 to 26 or 1 to 26 carbon atoms, where e is a substituted or unsubstituted aryl group in the alkyl or alkene chain. 13 is the number of C, which is from 1 to the number of carbons in the alkyl or alkene chain, preferably 1 to 4, and may contain one or an odd number of chlorine atoms, provided that there are no chlorines at the end of the residue and that the number of double bonds in the alkylene residue is a minimum of 1 to the number of theoretically possible cumulated double bonds, and that the double bonds are preferably neither cumulated nor conjugated; R 6 = 13 C e -chloro-alkyl residue, preferably having 0 to 26 or 1 to 26 carbon atoms, where e is a chloro-alkyl residue in the alkyl residue, in particular of the formula 13 C e -C n H 2n+1-y Cl y of 13 C is the number of carbons, n being 1 to 26, and y is the number of chlorine atoms, being 2 to 26, but preferably being 2 to 25; R 7 = 13 C f -alkylene residue, preferably having 0 to 22 carbon atoms, f is the number of carbon atoms in the alkene chain 13 is the number of C, which is from 1 to the number of carbon atoms in the alkene chain, preferably 1 to 4, and may contain one or an odd number of chlorine atoms; the number of double bonds in the alkylene residue is a minimum of 1 to the number of theoretically possible cumulated double bonds, and the double bonds are preferably neither cumulated nor conjugated; R 8 =13 C f -Chloro-C n - an alkyl residue, preferably having 0 to 22 carbon atoms, in particular having the formula 13 C f -C n H 2n-y Cl y wherein n is 0 to 22, and y is the number of chlorine atoms, which is 0 to 22, but preferably 0 to 21; R 9 = 13 C g - an alkyl or alkene residue, which, if alkyl, preferably has 0 to 4 carbon atoms and, if alkylene, has 3 or 4 carbon atoms, where g is a 2-membered group in the alkyl or alkene chain; 13 is the number of C, which is from 1 to the number of carbons in the alkyl or alkene chain, preferably 1 to 4, and may contain one double bond; R 10 = 13 C g -(chloro)-alkyl, preferably having 0 to 4 carbon atoms and containing 0, 1 or 2 chlorine atoms; R 9 = 13 C g - for alkyl residues, R 9 In some preferred embodiments, R 9 =R 10 = 13 C g - an alkyl residue; a, b, c, d, e, f, g are, independently of one another, integers from 1 to the number of carbon atoms in the respective alkyl or alkylene residue; in some preferred embodiments, a, b, c, d, e, f, g are each 1-4.

[0030] Here, in the present invention, *= 13 Note that C represents a carbon at the indicated position in the formula including the necessary hydrogen atoms (i.e., 0-3 hydrogen atoms) required to satisfy the valence of the carbon atom at the indicated position (as is commonly done in chemical formulas).

[0031] In the present disclosure, 13 C 指数 is the exponential number of carbon atoms in the given formula below. 13 Note also that this refers to substitution at the C carbon atom, and does not mean that an indexed carbon number is added. For example, 13 C3-C6H 12 has 3 of its 6 carbon atoms 13 C isotope substitution. 13 The exact position of the C isotope is 13 C 指数 It may be indicated by a number before the term, e.g. 2,3,5- 13 C3-C6H 12 has 3 of its 6 carbon atoms 13 C isotopes, meaning that they are in chain positions 2, 3 and 5. 13 C 指数 It will also be appreciated that the does not necessarily have to precede the rest of the formula, and in some cases may be better off in the middle or at the end of the formula to provide a clearer structure and / or to enhance comprehension.

[0032] Compound (1) is commercially available 13 C-labeled alcohol.

[0033] In a preferred embodiment, R 1 is R 2 has the same chain length as

[0034] In a preferred embodiment, R 3 is R 4 has the same chain length as

[0035] In a preferred embodiment, R 5 is R 6 has the same chain length as

[0036] In a preferred embodiment, R 7 is R 8 has the same chain length as

[0037] In a preferred embodiment, R 9is R 10 has the same chain length as

[0038] The method according to Scheme 4 is for compounds having a total chain length of 10 to 40 carbon atoms. 13 It should also be noted that this is provided as a condition for use only in preparing C-labeled chlorinated paraffins.

[0039] Unsaturated aldehydes (4) and (6), unsaturated alcohols (9) and (12), with or without chlorine in the carbon chain, can be prepared by methods known in the art. For example, an alcohol can be oxidized according to the Swern reaction and then reacted with a Wittig salt to provide an aldehyde having a longer chain than the starting alcohol. However, there is no particular limitation on the method by which aldehydes (4) and (6) or alcohols (9) and (12) can be prepared.

[0040] In some preferred embodiments of the present invention, aldehydes (4), (6) or alcohols (9) and (12) are prepared from unsaturated fatty acids. For example, this can be done by A) first providing an unsaturated fatty acid or a mixture of unsaturated fatty acids, then Ca) converting one or more unsaturated fatty acids into the corresponding alkenol or mixture of alkenols, or Da) converting one or more unsaturated fatty acids into the corresponding alkenal or mixture of alkenals. These embodiments are particularly useful for the synthesis of medium- and long-chain CPs (MCCPs and LCCPs).

[0041] In some preferred embodiments of the present invention, the alkene in step V) of the process of the present invention is prepared from an unsaturated fatty acid via the following steps: A) providing an unsaturated fatty acid or a mixture of unsaturated fatty acids; Ca) converting one or more unsaturated fatty acids into a corresponding alkenol or mixture of alkenols; and Cb1) reducing an alkenol or mixture of alkenols to the corresponding alkene or mixture of alkenes; or Cc1) replacing one or more alcohol groups with one or more leaving groups, preferably tosylates; Cc2) coupling an alkyl to the previous alcohol carbon, thereby removing the leaving group and forming an alkene or mixture of alkenes; or Da) converting one or more unsaturated fatty acids into a corresponding alkenal or mixture of alkenals; and Db1) coupling an alkenal or a mixture of alkenals with a Wittig salt to form the corresponding alkene or a mixture of alkenes.

[0042] Another further embodiment of the present invention comprises: 13 C-labeled or unlabeled unsaturated fatty acids or 13 Mixture of C-labeled or unlabeled unsaturated fatty acids 13 C-labeled or unlabeled chlorinated paraffins or 13 By converting to a mixture of C-labeled or unlabeled chlorinated paraffins, preferably having no geminal or terminal chlorine atoms in the structure, 13 A method for preparing C-labeled or unlabeled chlorinated paraffins.

[0043] In a preferred embodiment of the invention, the method comprises the steps of: A) 13 C-labeled or unlabeled unsaturated fatty acids or 13 providing a mixture of C labeled or unlabeled unsaturated fatty acids; Ba) chlorinating one or more unsaturated fatty acids; and Bb) decarboxylating the resulting chlorinated acid or acids; or Ca) converting one or more unsaturated fatty acids into a corresponding alkenol or mixture of alkenols; and Cb1) reducing an alkenol or mixture of alkenols to the corresponding alkene or mixture of alkenes; and Cb2) chlorinating the resulting alkene or mixture of alkenes; or Cc1) replacing one or more alcohol groups with one or more leaving groups, preferably tosylates; Cc2) coupling an alkyl to the previous alcohol carbon, thereby removing the leaving group and forming an alkene or mixture of alkenes; and Cc3) chlorinating the resulting alkene or mixture of alkenes; or Cd) chlorinating an alkenol or a mixture of alkenols; or Da) converting one or more unsaturated fatty acids into a corresponding alkenal or mixture of alkenals; and Db1) coupling an alkenal or a mixture of alkenals with a Wittig salt to form the corresponding alkene or a mixture of alkenes; Db1a) at least one in the coupling group 13 A step in which a Wittig salt having a C-labeled carbon atom may be used; and Db2) chlorinating the obtained alkene or mixture of alkenes Includes.

[0044] These methods can be illustrated as follows in Schemes 5 and 6, where alpha-linolenic acid is used as an example for illustrative purposes only (though the methods are of course not limited to linolenic acid): Scheme 5: [ka] Scheme 6: [ka]

[0045] In a preferred embodiment, the fatty acid used in this method is selected from C11-C24 unsaturated fatty acids, preferably C11-C24 polyunsaturated fatty acids, more preferably and even more preferably selected from, but not limited to, the following examples as well as mixtures thereof or optionally with other fatty acids: 9Z,12Z-Octadecadienoic acid (linoleic acid, C18:2); 9Z,12Z,15Z-Octadecatrienoic acid (alpha-linolenic acid, C18:3); 6Z,9Z,12Z-Octadecatrienoic acid (gamma-linolenic acid, C18:3); 6Z,9Z,12Z,15Z-Octadecatetrawnoic acid (stearidonic acid, C18:4); 10Z,13Z-nonadecadienoic acid (C19:2); 5Z,8Z,11Z-icosatrienoic acid (Mead acid, C20:3); 8Z,11Z,14Z-eicosatrienoic acid (homo-gamma-linolenic acid, C20:3); 11Z,14Z,17Z-eicosatrienoic acid (C20:3); 5Z,8Z,11Z,14Z-eicosatetraenoic acid (arachidonic acid, C20:4); 5Z,8Z,11Z,14Z,17Z-Eicosapentaenoic acid (EPA, C20:5).

[0046] Even more preferably, in some embodiments, the fatty acid is 9Z,12Z-octadecadienoic acid (linoleic acid, C18:2), 9Z,12Z,15Z-octadecatrienoic acid (alpha-linolenic acid, C18:3), 6Z,9Z,12Z-octadecatrienoic acid (gamma-linolenic acid, C18:3), 6Z,9Z,12Z,15Z-octadecatrienoic acid (stearidonic acid, C18:4), 10Z,13Z-nonadecadienoic acid (C19:2). , 5Z,8Z,11Z-eicosatrienoic acid (mead acid, C20:3), 8Z,11Z,14Z-eicosatrienoic acid (homo-gamma linolenic acid, C20:3), 11Z,14Z,17Z-eicosatrienoic acid (C20:3), 5Z,8Z,11Z,14Z-eicosatetraenoic acid (arachidonic acid, C20:4), 5Z,8Z,11Z,14Z,17Z eicosapentaenoic acid (EPA, C20:5), and mixtures thereof.

[0047] In another embodiment, the present invention has no geminal or terminal chlorine atoms in the structure, At least two chlorine atoms in the main chain; At least one, especially 2 to 8 carbon atoms in the main chain 13 is replaced by a C atom, 13 Regarding C-labeled chlorinated paraffins.

[0048] Preferably, these 13 C-labeled chlorinated paraffins have the general formula 13 C m -C p H 2p+2-x Cl x where the variables have the following meanings: m is an integer from 1 to p, particularly from 2 to 8; p is an integer of 2 to 38, preferably 8 to 38, particularly 8 to 30; x is 2 to p-2, preferably 4 to p-2, preferably for SCCPs 4 to 6, especially 4 or 6, for MCCPs 6 to 8, especially 6 or 8, for LCCPs 8 to 10, especially 8 or 10, in one particularly preferred embodiment 4 or 6.

[0049] Optionally, and in some embodiments of the present invention, preferably, these 13 C-labelled chlorinated paraffins are prepared according to the method according to the invention outlined above.

[0050] In yet another embodiment, the present invention provides a compound having no geminal or terminal chlorine atoms in the structure, and optionally, in some embodiments, preferred as described above. 13 C-labeled chlorinated paraffins, General formula A [ka] , Or general formula B [ka] , or general formula D [ka] or general formula E [ka] It can be represented by either wherein the variables and residues have the meanings defined above. 13 Regarding C-labeled chlorinated paraffins.

[0051] In yet another embodiment, the present invention provides a compound having no geminal or terminal chlorine atoms in the structure, and optionally, in some embodiments, preferred as described above. 13 C-labeled chlorinated paraffins, General formula A [ka] where *= 13 C, where R* is as defined above, or i) 6,7,8- 13C3-2,3,5,6-tetrachlorooctane or 2,3,5,6-tetrachlorooctane-6,7,8- 13 C3 formula [ka] , ii) 1,2,9,10- 13 C4-2,3,8,9-Tetrachlorodecane [ka] iii) 9,10,11- 13 C3-2,3,5,6,8,9-Hexachloroundecane or 2,3,5,6,8,9-Hexachloroundecane-9,10,11- 13 C3 formula [ka] , iv) 11,12,13- 13 C3-3,4,6,7,10,11-Hexachlorotridecane or 3,4,6,7,10,11-Hexachlorotridecane-11,12,13- 13 C3 formula [ka] , v) 1,2,9,10- 13 C4-2,3,5,6,8,9-Hexachlorodecane-1,2,9,10- 13 C4 or 2,3,5,6,8,9-Hexachlorodecane-1,2,9,10- 13 C4 formula [ka] , vi) 6,7,8- 13 C3-2,3,5,6,8,9,11,12-octachlorotridecane or 2,3,5,6,8,9,11,12-octachlorotridecane-6,7,8- 13 C3 formula [ka] , vii) 10, 11, 12- 13 C3-2,3,5,6,9,10-Hexachlorododecane [ka] ,or viii) 10, 11, 12- 13 C3-2,3,5,6,8,9-Hexachlorododecane [ka] , ix) 1,2,3- 13 C3-3,4,7,8,11,12-Hexachlorotetradecane [ka] , x)13,14,15- 13 C3-3,4,7,8,12,13-Hexachloropentadecane [ka] , xi) 1,2,3- 13 C3-3,4,8,9,13,14-Hexachlorohexadecane [ka] , xii) 1,2,3- 13 C3-3,4,12,13,15,16,18,19-octachloro-n-heneicosane, [ka] and mixtures thereof; wherein * is as defined above. 13 Regarding C-labeled chlorinated paraffins.

[0052] In one embodiment of the present invention, those of i), iii), iv) and v) are preferred.

[0053] In yet a further embodiment, the present invention relates to a mixture of chlorinated paraffins comprising a C-labelled chlorinated paraffin having no geminal chlorine atoms and no terminal chlorine atoms in its structure, prepared as described above according to the present invention or according to the method of the present invention as described above. 13

[0054] In yet another further embodiment, the present invention relates to the use of a C-labelled chlorinated paraffin having no geminal chlorine atoms and no terminal chlorine atoms in its structure, prepared as described above according to the present invention or according to the method of the present invention as described above, as an internal standard for the quantitative analysis of analytical methods, in particular very short-chain chlorinated paraffins (vSCCP, <C10), short-chain chlorinated paraffins (SCCP, C10-C13), medium-chain chlorinated paraffins (MCCP, C14-C17) and long-chain chlorinated paraffins (LCCP, C18-C30). 13

[0055] Yet another embodiment of the present invention is the use of a C-labelled chlorinated paraffin having no geminal chlorine atoms and no terminal chlorine atoms in its structure, prepared as described above according to the present invention or according to the method of the present invention as described above, as a reference material for the metabolism and toxicity analysis of chlorinated paraffins. 13

[0056] A further embodiment of the present invention is 9,10,11- 13 C3-1,2,4,5,8,9-hexachloroundecane, 10,11,12- 13 C3-1,2,5,6,9,10-hexachlorododecane, 11,12,13- 13 C3-1,2,6,7,10,11-hexachlorotridecane, 12,13,14- 13 C3-1,2,7,8,11,12-hexachlorotetradecane, 13,14,15- 13 C3-1,2,7,8,12,13-hexachloropentadecane, 14,15,16-​​​13 C3-1,2,8,9,13,14-Hexachlorohexadecane, 1,2,9,10- 13 C4-2,3,8,9-Tetrachlorodecane, 8,9,10- 13 C3-1,2,4,5,7,8-Hexachlorodecane, 1,2,3- 13 C3-3,4,12,13,15,16,18,19-Octachloro-n-heneicosane and mixtures thereof, in particular 1,2,9,10- 13 C4-2,3,8,9-tetrachlorodecane or 8,9,10- 13 The present invention relates to chlorinated paraffins selected from the group consisting of C3-1,2,4,5,7,8-hexachlorodecane.

[0057] The present invention in at least another embodiment provides an internal standard for analytical methods, particularly for the quantitative analysis of vSCCP, SCCP, MCCP, and LCCP, comprising: According to the present invention, there is provided a method for preparing a chlorine-containing compound having no geminal or terminal chlorine atoms in its structure, as described above or prepared according to the method of the present invention as described above. 13 One or more of C-labeled chlorinated paraffins, 9,10,11- 13 C3-1,2,4,5,8,9-Hexachloroundecane, 10,11,12- 13 C3-1,2,5,6,9,10-Hexachlorododecane, 11,12,13- 13 C3-1,2,6,7,10,11-Hexachlorotridecane, 12,13,14- 13 C3-1,2,7,8,11,12-Hexachlorotetradecane, 13,14,15- 13 C3-1,2,7,8,12,13-Hexachloropentadecane, 14,15,16- 13 C3-1,2,8,9,13,14-Hexachlorohexadecane, 1,2,9,10- 13 C4-2,3,8,9-Tetrachlorodecane, 8,9,10- 13 C3-1,2,4,5,7,8-Hexachlorodecane, 1,2,3- 13C3-3,4,12,13,15,16,18,19-Octachloro-n-heneicosane and mixtures thereof, in particular 1,2,9,10- 13 C4-2,3,8,9-tetrachlorodecane or 8,9,10- 13 one or more chlorinated paraffins selected from the group consisting of C3-1,2,4,5,7,8-hexachlorodecane; Or 9,10,11- 13 C3-1,2,4,5,8,9-Hexachloroundecane, 10,11,12- 13 C3-1,2,5,6,9,10-Hexachlorododecane, 11,12,13- 13 C3-1,2,6,7,10,11-Hexachlorotridecane, 12,13,14- 13 C3-1,2,7,8,11,12-Hexachlorotetradecane, 13,14,15- 13 C3-1,2,7,8,12,13-Hexachloropentadecane, 14,15,16- 13 C3-1,2,8,9,13,14-Hexachlorohexadecane, 1,2,9,10- 13 C4-2,3,8,9-tetrachlorodecane, 13 C3-1,2,4,5,7,8-Hexachlorodecane, 1,2,3- 13 C3-3,4,12,13,15,16,18,19-Octachloro-n-heneicosane and mixtures thereof, in particular 1,2,9,10- 13 C4-2,3,8,9-tetrachlorodecane or 8,9,10- 13 one or more mixtures of chlorinated paraffins selected from the group consisting of C3-1,2,4,5,7,8-hexachlorodecane, and According to the present invention, there is provided a method for preparing a chlorine-containing compound having no geminal or terminal chlorine atoms in its structure, as described above or prepared according to the method of the present invention as described above. 13 One or more other C-labeled chlorinated paraffins The present invention relates to an internal standard that comprises or consists of:

[0058] In a preferred variant of this embodiment, these internal standards for the analytical method are:13 C m -C p H 2p+2-x Cl x m is an integer between 1 and p, in particular between 2 and 8; p is an integer between 8 and 30; x=2 to p-1, preferably between 2 and 10, or 2 to 7 when p=8, or x=2 to p-2, preferably between 4 and p-2; 13 The C-labeled single-stranded mixture has a chlorine content of 45-75% by weight as calculated from NMR and chlorine titration analyses.

[0059] Deuterium atoms and 13 C atoms are to be understood as naturally occurring. Thus, any reference to substitution (or similar formulation) in the context of the present invention when relating to atoms of the glycerol or alkanol moieties is to be understood as an intentional substitution, and not as a naturally occurring deuterium or 13 C atoms are not considered.

[0060] The present invention offers several advantages over the prior art, some of which are: 13 C-labeled chlorinated paraffins, especially those that have neither geminal nor terminal chlorine atoms 13 The method of the present invention for preparing C-labeled chlorinated paraffins can provide these CPs with high reliability, good yield and high purity. New 13 C-labeled chlorinated paraffins, especially those that have neither geminal nor terminal chlorine atoms 13 C-labeled chlorinated paraffins have high purity and very well-defined chlorine content, which also makes the quantification of CPs accurate when CPs are used as standards, especially internal standards. New 13 C-labeled chlorinated paraffins, especially those that have neither geminal nor terminal chlorine atoms 13 C-labeled chlorinated paraffins are very well suited as reference materials since they have chlorine patterns similar to CP analytes found in technical mixtures or the environment. New 13 C-labeled chlorinated paraffins, especially those that have neither geminal nor terminal chlorine atoms 13 Reliable preparation of C-labeled chlorinated paraffins ensures that they can be used as certified reference materials (CRMS) for CP analysis.

[0061] The present invention will now be described in more detail with reference to the following non-limiting examples. The following illustrative non-limiting examples are provided to further describe the embodiments presented herein. Those skilled in the art will appreciate that variations of these examples are possible within the scope of the present invention. EXAMPLES

[0062] General synthesis procedure: 13 Synthesis of C-labeled 1-bromoalkanes and 1-bromoalkenes (2 and 16). General Procedure A: 13 C-labeled n-alcohols (1 or 15) were converted to bromides (2 or 16) by conventional methods, either by reaction with HBr-H2SO4 or PBr3; or, in some cases, the alcohol was first transferred to a tosylate, which was then reacted with LiBr to form the bromide.

[0063] Continued PBr 3 A typical procedure for the reaction with is as follows: 13 C-labeled n-alcohol (1) (3 mmol) and pyridine (75 mg) were mixed in pentane (5 ml) and cooled to -40°C. A solution of phosphorus tribromide (32 mg, 1.2 mmol) in pentane (2 ml) was added dropwise to the stirred solution. The mixture was stirred at cooled temperature for 1 h and the product was distilled off. The resulting product solution was diluted with pentane (10 ml) and washed with 5% HCl, 10% HNO3, water, and 5% KHCO3. The organic phase was dried over MgSO4, filtered, and concentrated. The residue was distilled to give the pure bromide (2) in 75-80% yield.

[0064] Synthesis of Wittig salt (3). General procedure B: Bromide (2) (10.0 mmol) and PPh3 (10.0 mmol) were mixed in dry acetonitrile (25 ml) and the mixture was heated to reflux for 72-48 h. The solvent was evaporated and the crude product was purified by column chromatography (silica; eluent EtOAc:MeOH, 90:10, 80:20-75:25). The resulting product was dried in vacuum to give a white solid 3 in 84% yield.

[0065] 13 Synthesis of C-labeled alkenes (5 and 7). General Procedure C: Wittig salt (3) (15.6 mmol) was mixed in dry THF (50 ml) under argon, cooled to -78 °C and n-butyllithium (2.5 M, 6.85 ml) was added dropwise. The reaction mixture was then warmed to -40 °C to -10 °C and maintained at this temperature for 1.5 h before being cooled again to -78 °C and aldehyde (4) (15.9 mmol) was added slowly. The reaction mixture was warmed to room temperature and stirred for 16 h and the reaction was quenched by the addition of saturated NH4Cl solution (50 ml). The two phases were separated, the aqueous phase was extracted with diethyl ether and the combined organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (silica; eluent petroleum ether) and eluted. 13 C-labeled alkenes (5) were obtained in 85–90% yields.

[0066] Using 2 equivalents of Wittig salt (3) and 1 equivalent of dialdehyde (6), 13 C-labeled alkene (7) was synthesized similarly.

[0067] 13 Synthesis of C-labeled alkenes (11 and 14). General Procedure D: a) Grignard Reagent 8 Magnesium (1.75 g, 72.0 mmol), dry diethyl ether (6 ml) and a crystal of iodide were added (under argon) with a few drops of bromide (2) in dry diethyl ether until the reaction started. A solution of bromide (2) (total 53.41 mmol) in diethyl ether (18 ml) was added dropwise at such a rate as to maintain a gentle reflux. After the addition was complete, the mixture was refluxed for 1 h. The mixture was cooled and more diethyl ether (2.5 ml) was added. The mixture (ca. 2 M) was used directly in the synthesis of 11 or 14.

[0068] b) Tosylates 10 and 13 p-Toluenesulfonyl chloride (7.72 g; 40.5 mmol) in dry DCM (50 ml) was added via a dropping funnel to a solution of alcohol (9; 36.8 mmol) and triethylamine (11.3 ml; 80.9 mmol) in dry dichloromethane (200 ml) at 0° C. under an argon atmosphere. The reaction mixture was stirred at 0° C. for 15 min and then at room temperature overnight (18 h). The reaction was quenched with water (250 ml). The two phases were separated and the aqueous phase was extracted with DCM (3×100 ml). The combined organic phase was washed with water, 10% NaHCO3 and water (all 200 ml) and dried over MgSO4. The crude product was purified by column chromatography (silica; eluent petroleum ether:DCM, 60:40, 50:50 to 25:75) to give the tosylate 10 in 80-85% yield.

[0069] The ditosylate 13 was similarly prepared from the diol compound 12 (1 equiv.), triethylamine (8 equiv.) and p-toluenesulfonyl chloride (2.2 equiv.) in DCM. The crude product was purified by column chromatography (silica; eluent petroleum ether:DCM, 60:40, 50:50 to 25:75) to give the tosylate 13 as a white solid. Recrystallization in methanol or dichloromethane was also used, which gave the white crystalline product in 34-55% yield.

[0070] c) Cross-coupling reaction of alkenes 11 and 14 A solution of 8 in diethyl ether (approximately 2 M) under argon was cooled to -75 °C and a solution of 10 (50 mmol) in THF (50 ml) and dilithium tetrachlorocuprate (10 mmol) (0.1 M solution in THF, 100 ml) were added. The temperature was slowly raised to approximately -30 °C and maintained for 15 min. The mixture was once again cooled to -70 °C and further dilithium tetrachlorocuprate solution was added (0.2 ml, 0.02 mmol), then the temperature was slowly raised and the mixture was stirred at room temperature overnight. Silica (50 g) was added to the mixture and the solvent was evaporated. The dry residue was poured onto the top of a column packed with silica and eluted with heptane. This gave the pure alkene 11 in 50-60% yield.

[0071] Using 2 equivalents of Grignard reagent (8) and 1 equivalent of ditosylate (13), 13 C-labeled alkene (14) was synthesized similarly.

[0072] Synthesis of tetraethylammonium trichloride Et4N(Cl)3: A solution of tetraethylammonium chloride (Et4NCl) in DCM was saturated with Cl2 and then the solvent was removed in vacuo to give a yellow solid which was stored under argon for later use in the chlorination reaction.

[0073] 13 Chlorination and synthesis of C-labeled CPs (A, B, D and E). General procedure X: A solution of EtNCl (1.5-2.0 equiv. for each C=C bond) in DCM was slowly added via syringe to a solution of the substrate in DCM (5, 0.3 M) at -78 °C under an argon atmosphere until the reaction mixture turned yellow. The mixture was stirred at -78 °C for 20 min, and when the yellow color disappeared, more trichloride solution was added.

[0074] After quenching the reaction with pent-1-ene, the mixture was allowed to warm to room temperature to dissolve the EtNCl solid that had formed in the reaction. The solvent was removed in vacuo and the residue was treated with diethyl ether, again precipitating EtNCl, the solid was filtered off, washed with EtO, and the filtrate was evaporated to dryness. The crude product was further purified by column chromatography. All 13 The C-labeled product was characterized by NMR and GC-MS.

[0075] Synthesis example: In order to further understand the present invention, the following 13 C-labeled CP is given as an example, but the present invention is not limited thereto.

[0076] 13 Synthesized from C3-1-propanol and linear unsaturated aldehyde (minimum one double bond in the carbon chain) 13 C3-labeled CP (Scheme 1) was taken as an example. 13 The synthesis of C3-2,3,5,6,8,9-hexachlorododecane is described in detail below.

[0077] Examples: 9, 10, 11- 13 Synthesis of C3-2,3,5,6,8,9-hexachlorododecane [ka]

[0078] 13 C3-1-Bromopropane 13C3-1-propanol (0.97 g, 15.4 mmol) and pyridine (375 mg, 4.75 mmol) were mixed in pentane (25 ml) and cooled to -40°C. A solution of phosphorus tribromide (1.68 g, 6.2 mmol) in pentane (10 ml) was added dropwise to the stirred solution. The mixture was stirred at cooling temperature for 1 h and the product was distilled off. The resulting product solution was diluted with pentane (50 ml) and washed with 5% HCl, 10% HNO3, water, 5% KHCO3. The organic phase was dried over MgSO4, filtered and concentrated. The residue was distilled to give 1.52 g (12.1 mmol) of 13 C3-1-bromopropane, a pale yellow oil, was obtained in 78.6% yield.

[0079] Triphenyl- 13 C3-Propylphosphonium bromide, Wittig salt 13 C3-1-Bromopropane (1.26 g, 10.0 mmol) and PPh3 (2.63 g, 10.0 mmol) were mixed in dry acetonitrile (25 ml), and the mixture was heated to reflux for 72 h. The solvent was evaporated and the crude product was purified by column chromatography (silica; eluent EtOAc:MeOH, 90:10, 80:20 to 75:25). The resulting product was dried in vacuum to give 3.26 g (8.4 mmol) of a white solid powder in 84% yield.

[0080] 9,10,11- 13 Synthesis of C3-undeca-2,5,8-triene Wittig salt (3.0 g, 7.8 mmol) was mixed in dry THF (25 ml) under argon, cooled to -78 °C, and n-butyl lithium (2.5 M, 3.4 ml) was added dropwise. The reaction mixture was then warmed to -40 °C to -10 °C and maintained at this temperature for 1.5 h, after which it was cooled again to -78 °C and aldehyde octa-3,6-dienal (1.0 g, 8.0 mmol) was added slowly. The reaction mixture was warmed to room temperature, stirred for 16 h, and the reaction was quenched by the addition of saturated NH4Cl solution (25 ml). The two phases were separated, the aqueous phase was extracted with diethyl ether, and the combined organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica; eluent petroleum ether) and eluted. 13 C-labeled alkenes 9,10,11- 13 C3-undeca,2,5,8-triene, 1.02 g (6.7 mmol) was obtained in a yield of 86%.

[0081] Synthesis of tetraethylammonium trichloride Et4N(Cl)3 A solution of tetraethylammonium chloride (Et4NCl) in DCM was saturated with Cl2 and then the solvent was removed in vacuo to give a yellow solid which was stored under argon for later use in the chlorination reaction.

[0082] 9,10,11- 13 C3-2,3,5,6,8,9-Hexachlorododecane A solution of EtNCl (9.26 g, 39.1 mmol, 6.0 equiv) in DCM (50 ml) was added to the 9,10,11- 13 A solution of 1.0 g of C3-undeca,2,5,8-triene, 6.5 mmol, in DCM (130 ml) was slowly added via syringe. The mixture was stirred at -78°C for 25 min and then quenched with excess pent-1-ene. The solvent was evaporated and the crude product was purified by column chromatography (eluent petroleum ether:diethyl ether=90:10) and recrystallization from n-hexane to give the target compound 9,10,11- 131.23 g (3.25 mmol) of C3-2,3,5,6,8,9-hexachlorododecane was obtained in 50.0% yield with a purity of >99.0% as analyzed by GC and NMR.

[0083] 13 Another example of C3-labeled CP 13 Starting from C3-propanol and unsaturated aldehydes with 1-2 double bonds, 13 C3-CP (Cl4 or Cl6) is 9,10,11- 13 It can be synthesized in the same manner as C3-2,3,5,6,9,10-hexachlorododecane. 13 The general structure of C3-Cl6-CP is shown in the following formula: [ka] , where m≧1, n≧0, R=n-alkyl, and R may be a proton (H).

[0084] Table 1 below does not include terminal and geminal chlorines. 13 C3-CP and 13 Table 2 shows C4-CPs containing one terminal chlorine, all prepared by the method according to the present invention. 13 Indicates C3-CP. [Table 1] [Table 2]

Claims

1. Preferably, the structure has no geminal or terminal chlorine atoms. １３ 1. A method for preparing a C-labeled chlorinated paraffin, comprising the steps of: V) providing an alkene or a mixture of alkenes, the alkene being having one or more α,β-ethylenically unsaturated double bonds in the main chain, One or more carbon atoms in the main chain １３ is substituted with a C atom, may have one chlorine atom or an odd number of chlorine atoms in the backbone, provided that there are no geminal or terminal chlorines on atoms that are part of an α,β-ethylenically unsaturated double bond; Steps and VI) reacting said alkene or mixture of alkenes with a trichloride, tribromide or triiodide, preferably a trichloride, more preferably a tetraalkylammonium trichloride, even more preferably tetraethylammonium trichloride; 23. A method comprising or consisting of:

2. Ia) at least one, two or more, or all of the carbon atoms in the main chain １３ Providing an alkanol substituted at a C atom; IIa) converting said alkanol to the corresponding bromide; IIIa) converting said bromide to a Wittig salt; IVa1) coupling the Wittig salt with an aldehyde to form an alkene having at least one α,β-ethylenically unsaturated double bond in its main chain, wherein the aldehyde has one, more than one, or all of the carbon atoms in the main chain １３ optionally substituted at a C atom, or IVa2) coupling the Wittig salt with a dialdehyde to form an alkene having at least two α,β-ethylenically unsaturated double bonds in its main chain, wherein the dialdehyde has one, more than one, or all of the carbon atoms in the main chain １３ optionally substituted at a C atom, or Ib) at least one, two or more, or all of the carbon atoms in the main chain １３ Providing an alkanol or alkenol, in particular an alkenol, substituted at a C atom, IIb) converting said alkanol or alkenol, in particular alkenol, into the corresponding halide, in particular bromide, IIIb) converting said halide to a Grignard reagent; IVb1) The Grignard is converted into a copper, nickel or palladium complex, in particular Li ２ CuCl ４ with a tosylate species, in particular made from an alcohol, via a carbon-carbon cross-coupling reaction catalyzed by １３ optionally substituted at a C atom, or IVb2) coupling said Grignard with a divalent tosylate species made from a diol via a carbon-carbon cross-coupling reaction to form an alkene having at least two α,β-ethylenically unsaturated double bonds in its backbone, said diol species having one, more than one or all of the carbon atoms in its backbone １３ Step 1: optionally substituted at a C atom The method of claim 1 further comprising:

3. 3. The method of claim 1 or 2, wherein the alkene is a straight-chain alkene or each of the alkenes is a straight-chain alkene.

4. In particular, it has an even number of chlorine atoms １３ To prepare C-labeled paraffin, Scheme 1a): 【Chemistry 1】 ； Or Scheme 1b): 【Chemistry 2】 ； Or Scheme 2a): 【Chemistry 3】 ； Or Scheme 2b): 【Chemistry 4】 ； Or Scheme 3: 【Chemistry 5】 ； Or Scheme 4: 【Chemistry 6】 ； The present invention is characterized in that the present invention complies with any one of the following: During the ceremony, R*= １３ C ａ -n-alkyl, * = １３ C; Ph = phenyl; Et = ethyl; R １ = １３ C ｂ an alkylene residue, which may contain one or an odd number of chlorine atoms, provided that there are no chlorines at the end of said residue and that the number of double bonds in said alkylene residue is a minimum of one up to the number of theoretically possible accumulated double bonds; R ２ = １３ C ｂ -chloro-alkyl residues, especially those of the formula １３ C ｂ -C ｎ H ２ｎ＋１－ｙ C ｙ and R ３ = １３ C ｄ an alkylene residue, which may contain one or an odd number of chlorine atoms, provided that there are no chlorines at the end of said residue and that the number of double bonds in said alkylene residue is a minimum of one up to the number of theoretically possible accumulated double bonds; R ４ = １３ C ｄ -chloro-alkyl residues, especially those of the formula １３ C ｄ -C ｎ H ２ｎ－ｙ C ｙ and R ５ = １３ C ｅ an alkylene residue, which may contain one or an odd number of chlorine atoms, provided that there are no chlorines at the end of said residue and that the number of double bonds in said alkylene residue is a minimum of one up to the number of theoretically possible accumulated double bonds; R ６ = １３ C ｅ -chloro-alkyl residues, especially those of the formula １３ C ｅ -C ｎ H ２ｎ＋１－ｙ C ｙ and R ７ = １３ C ｆ an alkylene residue, which may contain one or an odd number of chlorine atoms, the number of double bonds in said alkylene residue being a minimum of one up to the number of theoretically possible accumulated double bonds; R ８ = １３ C ｆ -Chloro-C ｎ - alkyl residues, especially those of the formula １３ C ｆ -C ｎ H ２ｎ－ｙ C ｙ and R ９ = １３ C ｇ - an alkyl or alkylene residue, which may contain one double bond; R １０ = １３ C ｇ -(chloro)-alkyl residue, R ９ = １３ C ｇ - if it is an alkyl residue, R ９ is equivalent to a, b, c, d, e, f, g are each independently an integer from 1 to the total number of carbon atoms in each of said alkyl or alkylene residues, preferably each 1 to 4; １３ C represents the number of carbons; n is an integer from 0 to 28, preferably from 1 to 28, representing the number of carbon atoms in each of said residues, each n value being independent of the n values ​​in the other residues; y is an integer from 0 to 28, preferably from 1 to n-1, and represents the number of chlorine atoms in each of said residues; The method according to claim 3.

5. The alkene is A) providing an unsaturated fatty acid or a mixture of unsaturated fatty acids; Ca) converting one or more unsaturated fatty acids into a corresponding alkenol or mixture of alkenols; and Cb1) reducing said alkenol or mixture of alkenols to the corresponding alkene or mixture of alkenes; or Cc1) replacing one or more alcohol groups with one or more leaving groups, preferably tosylates; Cc2) coupling an alkyl to the previous alcohol carbon, thereby removing the leaving group and forming an unsaturated bond; or Da) converting said one or more unsaturated fatty acids into a corresponding alkenal or mixture of alkenals; and Db1) coupling said alkenal or mixture of alkenals with a Wittig salt to give said corresponding alkene or mixture of alkenes.

5. The method according to claim 1, 3 or 4, characterized in that the fatty acid is prepared from an unsaturated fatty acid via

6. Unsaturated fatty acids or mixtures of unsaturated fatty acids １３ C-labeled or unlabeled chlorinated paraffin or １３ By converting to a mixture of C-labeled or non-labeled chlorinated paraffins, preferably having neither geminal nor terminal chlorine atoms in the structure, １３ 1. A method for preparing C-labeled or unlabeled chlorinated paraffins, comprising the steps of: A) １３ C-labeled or unlabeled unsaturated fatty acids or １３ Providing a mixture of C-labeled or unlabeled unsaturated fatty acids; Ba) chlorinating one or more of said unsaturated fatty acids; and Bb) decarboxylating the resulting chlorinated acid or acids; or Ca) converting one or more of said unsaturated fatty acids into a corresponding alkenol or mixture of alkenols; and Cb1) reducing said alkenol or mixture of alkenols to the corresponding alkene or mixture of alkenes; and Cb2) chlorinating the alkene or mixture of alkenes obtained; or Cc1) replacing one or more alcohol groups with one or more leaving groups, preferably tosylates; Cc2) coupling an alkyl to the previous alcohol carbon, thereby removing the leaving group and forming an unsaturated bond; and Cc3) chlorinating the alkene or mixture of alkenes obtained; or Cd) chlorinating said alkenol or mixture of alkenols; or Da) converting one or more of said unsaturated fatty acids into a corresponding alkenal or mixture of alkenals; and Db1) coupling said alkenal or mixture of alkenals with a Wittig salt to form the corresponding alkene or mixture of alkenes; Db1a) at least one in the coupling group １３ Wittig salts having C-labeled carbon atoms may be used; and Db2) chlorinating the alkene or mixture of alkenes obtained. A method comprising:

7. A compound having no geminal or terminal chlorine atoms in its structure, which may be prepared according to the method of any one of claims 1 to 6. １３ C-labeled chlorinated paraffins, at least two chlorine atoms in the main chain, and At least one, especially 2 to 8 carbon atoms of said backbone １３ is substituted by a C atom, Preferably, the general formula １３ C ｍ -C ｐ H ２ｐ＋２－ｘ Cl ｘ is represented by During the ceremony, m is an integer from 1 to p, in particular from 2 to 8; p is an integer from 2 to 38, preferably from 8 to 38, in particular from 8 to 30; x=2 to p-2, preferably 4 to p-2, more preferably for SCCP 4 to 6, especially 4 or 6, for MCCP 6 to 8, especially 6 or 8, for LCCP 8 to 10, especially 8 or 10; １３ C-labeled chlorinated paraffin.

8. Optionally, the compound according to claim 7 has no geminal or terminal chlorine atoms in the structure. １３ C-labeled chlorinated paraffins, General formula A 【Chemistry 7】 、 Or general formula B 【Chemistry 8】 、 Or general formula D 【Chemistry 9】 Or general formula E 【Chemistry 10】 It is represented by either wherein the variables have the meanings defined above in claim 4. １３ C-labeled chlorinated paraffin.

9. Preferably, the structure has no geminal or terminal chlorine atoms, as described in claim 7 or 8. １３ C-labeled chlorinated paraffins, General formula A 【Chemistry 11】 having In the formula, *= １３ C and R* is as defined above in claim 4; or or i) 6, 7, 8- of the following formula １３ C ３ -2,3,5,6-tetrachlorooctane or 2,3,5,6-tetrachlorooctane-6,7,8- １３ C ３ 【Chemistry 12】 、 ii) 1, 2, 9, 10- １３ C ４ -2,3,8,9-Tetrachlorodecane 【Chemistry 13】 、 iii) 9, 10, 11- of the following formula １３ C ３ -2,3,5,6,8,9-hexachloroundecane or 2,3,5,6,8,9-hexachloroundecane-9,10,11- １３ C ３ 【Chemistry 14】 、 iv) 11, 12, and 13 of the following formula １３ C ３ -3,4,6,7,10,11-hexachlorotridecane or 3,4,6,7,10,11-hexachlorotridecane-11,12,13- １３ C ３ 【Chemistry 15】 、 v) 1, 2, 9, 10- of the following formula １３ C ４ -2,3,5,6,8,9-Hexachlorodecane-1,2,9,10- １３ C ４ Or 2,3,5,6,8,9-hexachlorodecane-1,2,9,10- １３ C ４ 【Chemistry 16】 、 vi) 6,7,8- of the following formula １３ C ３ -2,3,5,6,8,9,11,12-octachlorotridecane or 2,3,5,6,8,9,11,12-octachlorotridecane-6,7,8- １３ C ３ 【Chemistry 17】 、 vii) 10, 11, 12- １３ C ３ -2,3,5,6,9,10-Hexachlorododecane 【Chemistry 18】 ,or viii) 10, 11, 12- １３ C ３ -2,3,5,6,8,9-Hexachlorododecane 【Chemistry 19】 、 ix) 1,2,3- １３ C ３ -3,4,7,8,11,12-Hexachlorotetradecane 【Chemistry 20】 、 x) 13, 14, 15- １３ C ３ -3,4,7,8,12,13-Hexachloropentadecane 【Chemistry 21】 、 xi) 1,2,3- １３ C ３ -3,4,8,9,13,14-Hexachlorohexadecane 【Chemical 22】 、 xii) 1, 2, 3- １３ C ３ -3,4,12,13,15,16,18,19-Octachloro-n-heneicosane 【Chemistry 23】 is selected from the group consisting of wherein * is as defined above. １３ C-labeled chlorinated paraffin.

10. No geminal or terminal chlorine atoms in the structure, according to any one of claims 7 to 9 or prepared according to any one of claims 1 to 6. １３ A mixture of chlorinated paraffins containing C-labeled chlorinated paraffins.

11. The method according to any one of claims 7 to 9 or prepared according to any one of claims 1 to 6, which has neither geminal nor terminal chlorine atoms in its structure, as an internal standard for analytical methods, in particular for the quantitative analysis of very short-chain chlorinated paraffins (vSCCPs, <C10), short-chain chlorinated paraffins (SCCPs, C10-C13); medium-chain chlorinated paraffins (MCCPs, C14-C17) and long-chain chlorinated paraffins (LCCPs, C18-C30). １３ Use of C-labeled chlorinated paraffins.

12. A compound according to any one of claims 7 to 9 or prepared according to any one of claims 1 to 6, which has no geminal or terminal chlorine atoms in its structure, as a reference material for the metabolism and toxicity analysis of chlorinated paraffins. １３ Use of C-labeled chlorinated paraffins.

13. 9, 10, 11- １３ C ３ -1,2,4,5,8,9-Hexachloroundecane, 10,11,12- １３ C ３ -1,2,5,6,9,10-Hexachlorododecane, 11,12,13- １３ C ３ -1,2,6,7,10,11-Hexachlorotridecane, 12,13,14- １３ C ３ -1,2,7,8,11,12-Hexachlorotetradecane, 13,14,15- １３ C ３ -1,2,7,8,12,13-Hexachloropentadecane, 14,15,16- １３ C ３ -1,2,8,9,13,14-Hexachlorohexadecane, 1,2,9,10- １３ C ４ -2,3,8,9-Tetrachlorodecane, 8,9,10- １３ C ３ -1,2,4,5,7,8-hexachlorodecane, and mixtures thereof, in particular 1,2,9,10- １３ C ４ -2,3,8,9-tetrachlorodecane or 8,9,10- １３ C ３ - chlorinated paraffins selected from the group consisting of 1,2,4,5,7,8-hexachlorodecane.

14. No geminal or terminal chlorine atoms in the structure, according to any one of claims 7 to 9 or prepared according to any one of claims 1 to 6. １３ one or more C-labeled chlorinated paraffins; One or more of the chlorinated paraffins according to claim 13, Or one or more of the chlorinated paraffins according to claim 13 and a chlorinated paraffin according to any one of claims 7 to 9 or prepared according to any one of claims 1 to 6, which has no geminal or terminal chlorine atoms in the structure. １３ Mixtures with one or more of C-labeled chlorinated paraffins An internal standard for an analytical method, in particular an internal standard for quantitative analysis of vSCCP, SCCP, MCCP, LCCP, comprising or consisting of:

15. １３ C ｍ -C ｐ H ２ｐ＋２－ｘ C ｘ wherein m is an integer from 1 to p, in particular from 2 to 8; p is an integer ≧8, in particular from 8 to 30; x=2 to p-1, preferably from 2 to 10, or x=2 to p-2, preferably from 4 to p-2; １３ 15. The internal standard for the analytical method according to claim 14, wherein the C-labelled single-stranded mixture has a chlorine content of 45-75% by weight calculated from NMR and chlorine titration analysis.

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