Process for preparing pentadecanoic acid

Abstract

The present invention generally refers to the technical field concerning processes related to the production of fat acids. Specifically, the present invention relates to a process for preparing a compound of Formula (I).

Description

[0001] PROCESS FOR PREPARING PENTADECANOIC ACID

[0002] FIELD OF THE INVENTION

[0003] The present invention generally refers to the technical field concerning processes related to the production of fat acids .

[0004] Speci fically, the present invention relates to a process for preparing a compound of Formula I : Formula I .

[0005] Background

[0006] Fat acids are liposoluble compounds formed by chains of carbon atoms provided with a terminal carboxylic group, which imparts acidic properties to them . The biosynthesis of fat acids mainly occurs in the liver, in the mammary gland, and in the adipose tis sue of higher organisms . The fat acids present in nature have an even overall number of carbon atoms , generally between 12 and 22 . The structure of fat acids allows them to be distinguished in two main categories : saturated and unsaturated fat acids . In the chain of saturated fat acids , there are no double bonds , unlike what occurs in unsaturated fat acids , in which there can be double bonds in a variable number (monounsaturated or polyunsaturated) . Animal fats , especially from ruminant animals ( for example , bovine and caprine ) , contain high amounts of saturated fats and are generally solid, while vegetable fats , usually richer in unsaturated fat acids , are fluid at room temperature .

[0007] Fat acids can vary in terms of the length of the hydrocarbon chain ( 1 to 21 carbon atoms ) . In this sense , a subdivision can be made according to the length of the chain into : short chain ( 1 to 5 carbon atoms ) , medium chain ( 6 to 12 carbon atoms ) , and long chain ( 13 to 21 carbon atoms ) . Pentadecanoic acid, in particular, is a saturated fat acid consisting of 15 carbon atoms . Like most linear fat acids with an odd number of carbon atoms , pentadecanoic acid is at much lower concentrations in nature compared to fat acids with an even number of carbon atoms .

[0008] Fat acids can be prepared by oxidation of primary alcohols , according to Scheme 1 :

[0009] R-CH2OH + oxidant - ► R-CO2H

[0010] Scheme 1 and by oxidative cleavage of alkenes according to Scheme 2 :

[0011] Scheme 2

[0012] Oxidative cleavage of alkenes and oxidation of primary alcohols occur with oxidants such as potassium permanganate , chromium (VI ) oxide , or potassium dichromate .

[0013] Potassium permanganate is toxic for waters with long-lasting ef fects , and its oxidi zing properties can react even explosively with organic substances in general and with easily oxidi zable inorganic compounds . Compounds containing chromium are highly toxic, corrosive , carcinogenic, and dangerous for the environment . Chromium trioxide is a very strong oxidant , and can ignite combustible material and organic substances , for example ethanol , upon simple contact . Chromium (VI ) reagents are commonly used for these oxidations . A family of Cr (VI ) reagents uses the complex CrO3(pyridine ) 2 • This family of reagents , in addition to the aforementioned problems regarding chromium toxicity, uses pyridine , which is a substance toxic by inhalation, ingestion, and absorption through the skin; it is also a suspected carcinogen and reduces male fertility .

[0014] Furthermore , during the oxidation reactions of alcohols , a part of the acid that is obtained reacts with the excess alcohol used and present in the reaction mixture , and the corresponding ester is formed; this impurity is then di f ficult to eliminate .

[0015] Fat acids can also be produced by preparing the Grignard reagent of alkyl halides and reacting it with carbon dioxide , according to Scheme 3 : Scheme 3 wherein X is a halogen .

[0016] Grignard reactions are widely used for producing intermediates and active pharmaceutical ingredients (API s ) . However, reactions with Grignard reagents have signi ficant issues . The first is the induction period, i . e . , the initial period during which no reaction occurs ; after this period, the reaction between the halide and the magnesium proceeds at an increasing rate . These reactions are di f ficult to control , and at the end of the induction period a considerable amount of reagent can have accumulated, with consequent safety and hazard problems that can lead to a runaway reaction . Furthermore , Grignard reagents react violently with water and ignite upon contact with air and therefore require highly controlled reaction systems that are di f ficult to obtain and to maintain throughout the reaction time .

[0017] The Applicant has addressed the problem of finding a process for producing fat acids on an industrial scale that allows to overcome the problems of the prior art , in particular with regard to process safety and productivity .

[0018] Summary of the Invention

[0019] The Applicant has overcome the problems of the prior art through a simpli fied and safe process , as defined in claim 1 . Such process allows to obtain fat acids of high purity, with high process yields and reduced preparation times , thus making it adapted to be made on an industrial scale .

[0020] In particular, the present invention relates to a process for preparing a compound of Formula I Formula I wherein n is between 6 and 21 ; said process comprising : a ) reacting a compound of Formula I I Formula I I , with carbon dioxide by electrolysis carried out in an electrochemical cell comprising an anode and a cathode , in an aprotic polar organic solvent , in the presence of at least one salt and a reductant , to obtain the compound of Formula I ; where

[0021] - n is between 6 and 21 ;

[0022] - X is a halogen;

[0023] - oxidation potential of the reductant and oxidation potential of the material with which the anode is made have a ratio b ) recovering the compound of Formula I .

[0024] Advantageously, the process of electrolysis carried out in an electrochemical cell according to the invention limits the formation of undesired by-products , thus obtaining high purity .

[0025] Another advantage is represented by the fact that the reaction rate can be controlled by adj usting the amount of current , so the process according to the invention meets high safety requirements .

[0026] Advantageously, the process according to the invention requires low energy consumption, in the face of high yield and selectivity; furthermore , the process according to the invention uses non-toxic reagents . This process can therefore be classi fied as a " green process" .

[0027] Equally advantageously, employing continuous flow reactors signi ficantly increases the productivity of the process .

[0028] Furthermore , the process of the present invention advantageously represents a strategic simpli fication in the economics ( in terms of time and costs ) and complexity of the process itsel f .

[0029] Further aspects , features , and advantages of the invention will become more apparent from the following detailed description .

[0030] Detailed Description of the Invention

[0031] For the purposes of the present invention, in the following description and claims , the definitions of numerical ranges comprise the single values within the range itsel f and the corresponding endpoints , unless otherwise speci fied .

[0032] For the purposes of the present invention, in the following description and claims , the term "comprising" further includes the terms "consisting of" or "consisting essentially of" .

[0033] Electrochemistry is that branch of chemistry which deals with processes involving the trans fer of electrons through an external electric circuit , and not by direct exchange as in oxidationreduction reactions . Electrosynthesis therefore represents a method of organic synthesis carried out in an electrochemical cell . Electrochemical reactors are divided in two typologies : undivided electrochemical cells , in which the cathode and the anode are immersed in the same electrolyte solution, or divided electrochemical cells , in which a porous diaphragm physically separates the anolyte from the catholyte , preventing the solutions from being remixed . These two configurations are suitable for those electrosynthesis carried out in galvanostatic mode , i . e . , by controlling an applied current .

[0034] The synthesis scheme ( Scheme 4 ) for preparing a compound of Formula I according to the process of the invention is reported below :

[0035] Scheme 4 . wherein n=6-21; X=C1, Br, I; A=cathode; B=anode .

[0036] Therefore, with reference to step a) of the process according to the invention, said step refers to the reaction between a compound of Formula II Formula II, with carbon dioxide by electrolysis carried out in an electrochemical cell, in an aprotic polar organic solvent, in the presence of at least one salt and a reductant, to obtain the compound of Formula I .

[0037] According to a preferred aspect of the invention, in step a) in the compound of Formula I and in the compound of Formula II, n=12.

[0038] Preferably, in step a) , X is selected from chlorine, bromine, and iodine; preferably bromine.

[0039] According to a preferred aspect of the invention, in step a) , oxidation potential of the reductant and oxidation potential of the material with which the anode is made have a ratio:

[0040] Said ratio < 1.0 indicates that the material with which the anode is made is not consumed under the electrolysis conditions, thus the anode is non-sacrif icial . Therefore, as intended in the following text and in the attached claims, the definition of the anode by the above ratio or by the definition "the anode is non-sacrif icial" are to be considered equivalent and usable interchangeably. Oxidation potentials of materials are known in the literature and easily accessible to a person skilled in the art. For example, the oxidation potentials of materials can be found in the handbook "Cynthia G. Zoski, Handbook of Electrochemistry, Elsevier Science, 2007, ISBN 978-0-444-51958-0". Advantageously, employing a non-sacrif icial anode allows the electrolysis to be carried out in a continuous flow reactor, thereby exponentially increasing the productivity of the process . Preferably, in step a) , the aprotic polar organic solvent is selected from nitriles, preferably acetonitrile, amides, preferably dimethylformamide and dimethylacetamide, dimethyl sulfoxide, heterocyclic organic solvents, preferably N-methyl pyrrolidone, N- octyl pyrrolidone, N-butyl pyrrolidone, or combinations thereof; preferably the aprotic polar organic solvent is dimethylformamide.

[0041] Preferably, in step a) , the compound of Formula II is at an initial concentration between 0.015 M and 0.67 M, preferably between 0.020 M and 0.60 M.

[0042] Preferably, in step a) , the salt is selected from tetraethylammonium tetrafluoroborate (TEABF4) , tetraethylammonium hexafluorophosphate (TEAPFg) , tetrabutylammonium tetrafluoroborate (TBABF4) , tetrabutylammonium hexafluorophosphate (TBAPFg) , lithium tetrafluoroborate (L1BF4) , tetraethylammonium perchlorate (TEACIO4) , tetrabutylammonium perchlorate (TBACIO4) , lithium perchlorate (LiClO4) , tetraethylammonium iodide (TEAI) , tetraethylammonium bromide (TEABr) , tetraethylammonium chloride (TEACI) , tetrabutylammonium iodide (TBAI) , tetrabutylammonium bromide (TBABr) , tetrabutylammonium chloride (TBAC1) , and a halide of an alkaline or alkaline earth metal, preferably selected from lithium chloride (LiCl) , sodium chloride (NaCl) , potassium chloride (KC1) , magnesium chloride (MgC12) , calcium chloride (CaC12) , lithium bromide (LiBr) , sodium bromide (NaBr) , potassium bromide (KBr) , magnesium bromide (MgBr2) , calcium bromide (CaBr2) , lithium iodide (Lil) , sodium iodide (Nal) , potassium iodide (KI) , magnesium iodide (Mgl2) , calcium iodide (Cal2) , or combinations thereof. Preferably, it is TBABr or TEABF4, possibly in combination with a halide of an alkaline or alkaline earth metal.

[0043] Preferably, in step a) , the salt is at an initial concentration between 0.01 M and 0.67 M, preferably between 0.05 M and 0.60 M.

[0044] Preferably, in step a) , the reductant is selected from triethanolamine (TEOA) , triethylamine (TEA) , diisopropylethylamine (DIPEA) , monoethanolamine, diethanolamine, Hantzsch ester, preferably TEOA. According to a preferred aspect, in step a) , the reductant is selected from 1 , 5-diazabicyclo [ 5.4.0 ] undec-7-ene (DBU) and 1,5,7- triazabicyclo [ 4.4.0 ] dec-5-ene (TBD) , more preferably the reductant is TBD.

[0045] Preferably, in step a) , the reductant is at an initial concentration between 0.015 M and 0.67 M, preferably between 0.020 M and 0.60 M .

[0046] According to a preferred aspect of the invention, in step a) , the electrochemical cell has an undivided or separated-cell configuration. Preferably, the electrochemical cell has an undivided configuration .

[0047] Preferably, in step a) , a carbon dioxide atmosphere is created inside the electrochemical cell, preferably the carbon dioxide atmosphere is created by carrying out vacuum-carbon dioxide cycles.

[0048] Preferably, in step a) , the electrolysis is carried out at a temperature between 0°C and 80°C.

[0049] According to a further preferred aspect of the invention, in step a) , the electrolysis is carried out at constant current.

[0050] Preferably, in step a) , when the electrolysis is carried out at constant current, the amount of applied current ranges from 2 mA to 100 mA.

[0051] Preferably, in step a) , the electrolysis is carried out at constant voltage.

[0052] Preferably, in step a) , when the electrolysis is carried out at constant voltage, the potential difference is between 0.2 V and 30 V.

[0053] Preferably, in step a) , the electrolysis is carried out for a total charge between 2 F / mol and 30 F / mol, more preferably between 2 F / mol and 15 F / mol.

[0054] According to a preferred aspect of the invention, in step a) , the cathode is made of a material selected from silver, graphite (C) , vitreous carbon (GC) , preferably reticulated vitreous carbon (RVC) or reticulated vitreous carbon foam (RVC foam) , nickel, preferably nickel foam, stainless steel, aluminium, platinum, gold, cobalt , titanium, copper, lead, tungsten, bronze lead, and tin; preferably, the cathode is made of silver or vitreous carbon ( GC ) .

[0055] According to a further preferred aspect of the invention, in step a ) , the anode is made of a material selected from graphite ( C ) , vitreous carbon ( GC ) , preferably reticulated vitreous carbon (RVC ) or reticulated vitreous carbon foam (RVC foam) , nickel , preferably nickel foam, stainless steel , aluminium, platinum, gold, cobalt , titanium, copper, lead, tungsten, bronze lead, and tin; preferably, the anode is made of graphite or vitreous carbon ( GC ) .

[0056] According to a further preferred aspect of the invention, in step a ) , the electrolysis is carried out in a flow reactor, by continuous feeding of a reaction mixture and carbon dioxide . Preferably, the flow reactor is selected from a plug- flow reactor, a chip- flow reactor, or a continuous stirred tank reactor ( CSTR) .

[0057] Preferably, in step a ) , the electrolysis is carried out by immersing the electrochemical cell in an ultrasonic bath . Preferably, the ultrasonic bath is of the pulsed or non-pulsed type . Preferably, the temperature is between 0 ° C and 80 ° C . Preferably, the ultrasound frequency is between 40 kHz and 130 kHz .

[0058] With reference to step b ) of the process according to the invention, said step refers to the recovery of the compound of Formula I . According to a preferred aspect , the recovery process is an isolation process ; generally, step b ) is a step that allows the compound of Formula I to be recovered from the reaction residues . More detailed isolation techniques can be considered by the person skilled in the art in case particular purity requirements are necessary .

[0059] Preferably, in step b ) , the reaction mixture subj ected to electrolysis in step a ) is diluted with a water-immiscible polar solvent , preferably with ethyl acetate and with an aqueous solution of ammonium chloride (NH4CI ) 1 M . Preferably, the biphasic solution is subj ected to stirring and allowed to decant . The aqueous phase is separated and re-extracted with ethyl acetate . Preferably, the organic phase of work-up is combined with that of back-extraction and washed with an aqueous solution of NH4CI 0 . 1 M . The organic solution is dried by adding sodium sulphate (Na2SC>4 ) , the sodium sulphate is then filtered of f . Preferably, the clear organic solution containing the compound of Formula I is concentrated under vacuum to obtain the compound of Formula I .

[0060] Preferably, in step b ) , the compound of Formula I is puri fied by dissolving the product in a water-immiscible organic solvent , preferably ethyl acetate , and adding a basic aqueous solution . After stirring the formed biphasic mixture , the compound of Formula I is in the form of a salt in the aqueous phase ; the two phases are separated . Preferably, an acid is added to the aqueous phase containing the product to obtain the puri fied compound o f Formula I .

[0061] Preferably, the compound of Formula I is subj ected to distillation at reduced pressure to obtain the puri fied compound of Formula I .

[0062] Preferably, in step b ) , the solid present in the reaction mixture subj ected to electrolysis in step a ) is separated by centri fugation or filtration . According to a pre ferred aspect , the solid is then washed with an aprotic polar organic solvent , preferably acetonitrile . Preferably, after washing, the solid is treated with hydrochloric acid and finally with water . Preferably, the puri fied solid thus obtained is dried to obtain the compound of Formula I .

[0063] Further details of the process according to the invention are reported below . In particular, the following exemplary embodiments are provided for illustrative purposes only and should not be construed as limiting the scope of protection defined by the appended claims .

[0064] List of Abbreviations

[0065] TEABF4 : tetraethylammonium tetrafluoroborate mA: milliampere mF : milli farad F / mol : farad per mole TEOA: triethanolamine

[0066] NH4CI : ammonium chloride

[0067] M: molar

[0068] NMR: nuclear magnetic resonance spectroscopy

[0069] CDCI3: deuterated chloroform

[0070] DMSO: dimethyl sulfoxide

[0071] ACN : acetonitrile

[0072] Rpm: revolutions per minute

[0073] Examples

[0074] The following examples are provided for illustrative purposes only; therefore, such examples should not be construed as limiting the scope of the invention.

[0075] Example 1. Preparation of pentadecanoic acid (employing a non- sacrificial anode) .

[0076] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) equipped with a magnetic stir bar was charged with 27.8 mg of 1-bromotetradecane (0.1 mmol, 29.8 pl, 0.033 M) , 30.0 mg of triethanolamine (TEOA, 0.2 mmol) , and 65 mg of TEABF4 (0.3 mmol, 0.099 M) . The vial was fitted with the appropriate screw cap equipped with a graphite (C) anode and a silver (Ag) cathode and was closed by a rubber septum. The air inside the vial was removed by vacuum and carbon dioxide (CO2) , with purity > 99.5%, was introduced. The vacuum-carbon dioxide cycle was performed three times to create the carbon dioxide atmosphere inside the vial. 3 mL of anhydrous acetonitrile were added and the mixture was stirred for 2 minutes while bubbling CO2.

[0077] The reaction mixture was then subjected to electrolysis at constant current (10 mA) for a total charge equal to 1.0 mF (10 F / mol) . At the end of the electrolysis, the screw cap was removed, the reaction mixture was transferred to a separatory funnel. The vial and the electrodes were washed with 10 mL of ethyl acetate and subsequently with 10 mL of an aqueous solution of NH4CI 1 M; the washings were charged in the separatory funnel containing the reaction mixture. The separatory funnel was subjected to stirring and the formed biphasic mixture was then allowed to decant. The phases were separated. The aqueous phase was extracted twice with 10 mL of ethyl acetate. The organic phases were combined, and the obtained organic solution was subsequently washed three times with 20 mL of an aqueous solution of NH4CI 0.1 M. The organic solution was dried by adding sodium sulphate (Na2SC>4) . The sodium sulphate was then filtered off, and the clear solution was concentrated under vacuum to obtain the compound of Formula I. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1- bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1- bromotetradecane and pentadecanoic acid.

[0078] Example 1-B: further isolation procedure of pentadecanoic acid.

[0079] At the end of the electrolysis, the solid present in the reaction mixture was centrifuged (7000 rpm, 5 minutes) , the liquid phase was discarded. The solid was washed with acetonitrile (5 mL) and subjected to centrifugation again, the washing solvent was discarded. The solid was suspended in hydrochloric acid (2 M, 5 mL) , stirred vigorously, and subjected to centrifugation again (9000 rpm, 20 min) , the liquid phase was discarded. The obtained white solid was washed with water (5 mL) and subjected to centrifugation (9000 rpm, 20 min) , the aqueous phase was discarded. The solid was dried under vacuum, obtaining purified pentadecanoic acid.

[0080] Example 2. Preparation of pentadecanoic acid (employing a salt) .

[0081] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) equipped with a magnetic stir bar was charged with 27.8 mg of 1-bromotetradecane (0.1 mmol, 29.8 pl, 0.033 M) , 30.0 mg of triethanolamine (TEOA, 0.2 mmol) , 18.4 mg of MgBr2 (0.1 mmol, 0.033 M) , and 65 mg of TEABF4 (0.3 mmol, 0.099 M) . The vial was fitted with the appropriate screw cap equipped with a graphite (C) anode and a silver (Ag) cathode and was closed by a rubber septum. The air inside the vial was removed by vacuum and carbon dioxide (CO2) , with purity > 99.5%, was introduced. The vacuum-carbon dioxide cycle was performed three times to create the carbon dioxide atmosphere inside the vial. 3 mL of anhydrous acetonitrile were added and the mixture was stirred for 2 minutes while bubbling CO2. The reaction mixture was then subjected to electrolysis at constant current (10 mA) for a total charge equal to 1.0 mF (10 F / mol) . At the end of the electrolysis, the screw cap was removed, the reaction mixture was transferred to a separatory funnel. The vial and the electrodes were washed with 10 mL of ethyl acetate and subsequently with 10 mL of an aqueous solution of NH4CI 1 M; the washings were charged in the separatory funnel containing the reaction mixture.

[0082] The separatory funnel was subjected to stirring and the formed biphasic mixture was then allowed to decant. The phases were separated. The aqueous phase was extracted twice with 10 mL of ethyl acetate. The organic phases were combined, and the obtained organic solution was subsequently washed three times with 20 mL of an aqueous solution of NH4CI 0.1 M. The organic solution was dried by adding sodium sulphate (Na2SC>4) . The sodium sulphate was then filtered off, and the clear solution was concentrated under vacuum to obtain the compound of Formula I. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1- bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1- bromotetradecane and pentadecanoic acid.

[0083] Example 3. Comparative example. Preparation of pentadecanoic acid (employing a sacrificial anode) .

[0084] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) equipped with a magnetic stir bar was charged with 27.8 mg of 1-bromotetradecane (0.1 mmol, 29.8 pl, 0.033 M) and 65 mg of TEABF4 (0.3 mmol, 0.099 M) . The vial was fitted with the appropriate screw cap equipped with a magnesium (Mg) anode and a silver (Ag) cathode and was closed by a rubber septum. The air inside the vial was removed by vacuum and carbon dioxide (CO2) , with purity > 99.5%, was introduced. The vacuum-carbon dioxide cycle was performed three times to create the carbon dioxide atmosphere inside the vial. 3 mL of anhydrous acetonitrile were added and the mixture was stirred for 2 minutes while bubbling CO2. The reaction mixture was then subjected to electrolysis at constant current (10 mA) for a total charge equal to 1.0 mF (10 F / mol) . At the end of the electrolysis, the screw cap was removed, the reaction mixture was transferred to a separatory funnel. The vial and the electrodes were washed with 10 mL of ethyl acetate and subsequently with 10 mL of an aqueous solution of NH4CI 1 M; the washings were charged in the separatory funnel containing the reaction mixture. The separatory funnel was subjected to stirring and the formed biphasic mixture was then allowed to decant. The phases were separated. The aqueous phase was extracted twice with 10 mL of ethyl acetate. The organic phases were combined, and the obtained organic solution was subsequently washed three times with 20 mL of an aqueous solution of NH4CI 0.1 M. The organic solution was dried by adding sodium sulphate (Na2SC>4) . The sodium sulphate was then filtered off, and the clear solution was concentrated under vacuum to obtain the compound of Formula I. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1-bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1- bromotetradecane and pentadecanoic acid. Yield: 25%.

[0085] Example 4. Comparative example. Preparation of pentadecanoic acid (employing a sacrificial anode and an ultrasonic bath) .

[0086] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) equipped with a magnetic stir bar was charged with 27.8 mg of 1-bromotetradecane (0.1 mmol, 29.8 pl, 0.033 M) and 65 mg of TEABF4 (0.3 mmol, 0.099 M) . The vial was fitted with the appropriate screw cap equipped with a magnesium (Mg) anode and a silver (Ag) cathode and was closed by a rubber septum. The air inside the vial was removed by vacuum and carbon dioxide (CO2) , with purity > 99.5%, was introduced. The vacuum-carbon dioxide cycle was performed three times to create the carbon dioxide atmosphere inside the vial. 3 mL of anhydrous acetonitrile were added and the mixture was stirred for 2 minutes while bubbling CO2. The reaction mixture was then subjected to electrolysis at constant current (10 mA) for a total charge equal to 1.0 mF (10 F / mol) by immersing the vial in a non-pulsed ultrasonic bath for the entire duration of the reaction (ultrasound frequency 40 kHz, ultrasound power 60 W) . The screw cap was removed, the reaction mixture was transferred to a separatory funnel. The vial and the electrodes were washed with 10 mL of ethyl acetate and subsequently with 10 mL of an aqueous solution of NH4CI 1 M; the washings were charged in the separatory funnel containing the reaction mixture. The separatory funnel was subjected to stirring and the formed biphasic mixture was then allowed to decant. The phases were separated. The aqueous phase was extracted twice with 10 mL of ethyl acetate. The organic phases were combined, and the obtained organic solution was subsequently washed three times with 20 mL of an aqueous solution of NH4CI 0.1 M. The organic solution was dried by adding sodium sulphate (Na2SC>4) . The sodium sulphate was then filtered off, and the clear solution was concentrated under vacuum. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1-bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1-bromotetradecane and pentadecanoic acid. Yield: 40%.

[0087] Example 5. Preparation of pentadecanoic acid (employing a non- sacrificial anode) .

[0088] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) , equipped with a magnetic stir bar, was charged with: 1- bromotetradecane (0.1 mmol, 27.7 mg) and TEABF4 (0.1 mmol, 21.7 mg) . The vial was fitted with the appropriate screw cap equipped with both a vitreous carbon (GC) anode and cathode and sealed by a rubber septum. The air inside the vial was removed by vacuum, and carbon dioxide (CO2) , with a purity of > 99.5%, was introduced. The vacuum- carbon dioxide cycle was performed three times to create a carbon dioxide atmosphere inside the vial. Anhydrous DMF (3 mL) was then added, and the mixture was subjected to stirring until the electrolyte was completely dissolved. CO2 was bubbled in the solution for about one minute, and 0.4 mmol of reductant was added through a Hamilton syringe. The reaction mixture was then subjected to electrolysis at a constant current equal to 25 mA for 1.5 hours. Once ended the electrolysis, the reaction mixture was treated with a solution of HC1 (2 M, 2 mL) and ethyl acetate (10 mL) . The two phases were transferred to a separatory funnel and then separated. The aqueous phase was extracted again with EtOAc (2 x 10 mL) , and the combined organic phases were washed with HC1 0.1 M (3 x 10 mL) , and then dried with Na2SO4. The organic solvent was evaporated, and the crude reaction product was dried on a rotary pump for 10 minutes. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1-bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1-bromotetradecane and pentadecanoic acid.

[0089] This process was tested with different reductants, obtaining the results reported in the following Table 1:

[0090] Table 1.

[0091] Example 6. Preparation of pentadecanoic acid (employing a non- sacrificial anode and TBD as reductant) .

[0092] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) , equipped with a magnetic stir bar, was charged with: 1- bromotetradecane (0.1 mmol, 27.7 mg) and TEABF4 (0.1 mmol, 21.7 mg) . The vial was fitted with the appropriate screw cap equipped with both a vitreous carbon (GC) anode and cathode and sealed by a rubber septum. The air inside the vial was removed by vacuum, and carbon dioxide (CO2) , with a purity of > 99.5%, was introduced. The vacuum- carbon dioxide cycle was performed three times to create a carbon dioxide atmosphere inside the vial. Anhydrous DMF (3 mL) was then added, and the mixture was subjected to stirring until the electrolyte was completely dissolved. CO2 was bubbled in the solution for about one minute, and 0.4 mmol of TBD was added through a Hamilton syringe. The reaction mixture was then subjected to electrolysis at a constant current equal to 25 mA for 1.5 hours. Once ended the electrolysis, the reaction mixture was treated with a solution of HC1 (2 M, 2 mL) and EtOAc (10 mL) . The two phases were transferred to a separatory funnel and then separated. The aqueous phase was extracted again with EtOAc (2 x 10 mL) , and the combined organic phases were washed with HC1 0.1 M (3 x 10 mL) , and then dried with Na2SO4. The organic solvent was evaporated, and the crude reaction product was dried on a rotary pump for 10 minutes. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1-bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1- bromotetradecane and pentadecanoic acid.

[0093] The results are reported in the following Table 2:

[0094] Table 2.

[0095] Example 7. Preparation of pentadecanoic acid (employing a non- sacrificial anode and DIPEA as reductant) .

[0096] A vial of the electrosynthesis device (ElectraSyn 2.0 equipment) , equipped with a magnetic stir bar, was charged with: 1- bromotetradecane (0.1 mmol, 27.7 mg) and TEABF4 (0.1 mmol, 21.7 mg) . The vial was fitted with the appropriate screw cap equipped with both a vitreous carbon (GC) anode and cathode and sealed by a rubber septum. The air inside the vial was removed by vacuum, and carbon dioxide (CO2) , with a purity of > 99.5%, was introduced. The vacuum- carbon dioxide cycle was performed three times to create a carbon dioxide atmosphere inside the vial. Anhydrous DMF (3 mL) was then added, and the mixture was subjected to stirring until the electrolyte was completely dissolved. CO2 was bubbled in the solution for about one minute, and 0.7 mmol (122 pl) of DIPEA was added through a Hamilton syringe. The reaction mixture was then subjected to electrolysis at a constant current equal to 30 mA for 1.5 hours. Once ended the electrolysis, the reaction mixture was treated with a solution of HC1 (2 M, 2 mL) and EtOAc (10 mL) . The two phases were transferred to a separatory funnel and then separated. The aqueous phase was extracted again with EtOAc (2 x 10 mL) , and the combined organic phases were washed with HC1 2 M (1 x 10 mL) , then with water (2 x 30 mL) , and then dried with Na2SO4. The organic solvent was evaporated, and the crude reaction product was dried on a rotary pump for 10 minutes. The crude residue obtained was analyzed by NMR spectroscopy (CDCI3, 400 MHz, diagnostic signals: 1- bromotetradecane : 3.30 ppm, pentadecanoic acid: 2.35 ppm) , evaluating the ratio between the diagnostic signals of 1- bromotetradecane and pentadecanoic acid.

[0097] The results are reported in the following Table 3:

[0098] Table 3.

Claims

CLAIMS1. A process for preparing a compound of Formula IFormula I wherein n=12; said process comprising: a) reacting a compound of Formula IIFormula II, with carbon dioxide by electrolysis carried out in an electrochemical cell, comprising an anode and a cathode, in an aprotic polar organic solvent, in the presence of at least one salt and a reducing agent, to obtain the compound of Formula I; where- n=12;- X is an halogen;- oxidation potential of the reductant and oxidation potential of the material with which the anode is made have a ratiob) recovering the compound of Formula I.

2. The process according to claim 1, wherein in step a) X is selected from chlorine, bromine and iodine; preferably is bromine.

3. The process according to any one of the preceding claims, wherein in step a) the aprotic polar organic solvent is selected from nitriles, preferably acetonitrile; amides, preferably dimethylformamide or dimethylacetamide; dimethyl sulfoxide; heterocyclic organic solvents, preferably N-methyl pyrrolidone, N- octyl pyrrolidone, N-butyl pyrrolidone, or combinations thereof; preferably, the aprotic polar organic solvent is dimethylformamide.

4. The process according to any one of the preceding claims, wherein in step a) the compound of Formula II is at an initial concentration between 0.015 M and 0.67 M, preferably between 0.020 M and 0.60 M .

5. The process according to any one of the preceding claims, wherein in step a) the salt is selected from tetraethylammonium tetrafluoroborate (TEABF4) , tetraethylammonium hexafluorophosphate (TEAPFg) , tetrabutylammonium tetrafluoroborate (TBABF4) , tetrabutylammonium hexafluorophosphate (TBAPFg) , lithium tetrafluoroborate (L1BF4) , tetraethylammonium perchlorate (TEACIO4) , tetrabutylammonium perchlorate (TBACIO4) , lithium perchlorate (LiClO4) , tetraethylammonium iodide (TEAI) , tetraethylammonium bromide (TEABr) , tetraethylammonium chloride (TEACI) , tetrabutylammonium iodide (TBAI) , tetrabutylammonium bromide (TBABr) , tetrabutylammonium chloride (TBAC1) , and a halide of an alkaline or alkaline earth metal selected from lithium chloride (LiCl) , sodium chloride (NaCl) , potassium chloride (KC1) , magnesium chloride (MgC12) , calcium chloride (CaC12) , lithium bromide (LiBr) , sodium bromide (NaBr) , potassium bromide (KBr) , magnesium bromide (MgBr2) , calcium bromide (CaBr2) , lithium iodide (Lil) , sodium iodide (Nal) , potassium iodide (KI) , magnesium iodide (Mgl2) , calcium iodide (Cal2) or combinations thereof, preferably it is TBABr, or TEABF4.

6. The process according to any one of the preceding claims, wherein in step a) the salt is at an initial concentration between 0.01 M and 0.67 M, preferably between 0.05 M and 0.60 M.

7. The process according to any one of the preceding claims, wherein in step a) the reductant is selected from triethanolamine (TEOA) , triethylamine (TEA) , diisopropylethylamine (DIPEA) , monoethanolamine, diethanolamine, Hantzsch ester, preferably is TEOA or DI PEA.

8. The process according to claims 1-6, wherein in step a) the reductant is selected from 1 , 5-diazabicyclo [ 5.4.0 ] undec-7-ene (DBU) and 1 , 5, 7-triazabicyclo [ 4.4.0 ] dec-5-ene (TBD) , preferably the reductant is TBD.

9. The process according to any one of the preceding claims, wherein in step a) the reductant is at an initial concentration between 0.015 M and 0.67 M, preferably between 0.020 M and 0.60 M.

10. The process according to any one of the preceding claims, wherein in step a) the electrochemical cell has an undivided configuration .

11. The process according to any one of the preceding claims, wherein in step a) a carbon dioxide atmosphere is created inside the electrochemical cell, preferably the carbon dioxide atmosphere is created by carrying out vacuum-carbon dioxide cycles.

12. The process according to any one of the preceding claims, wherein in step a) the electrolysis is carried out at constant current .

13. The process according to claim 12, wherein in step a) the electrolysis is carried out with an amount of applied current ranging from 2 mA to 100 mA.

14. The process according to any one of the preceding claims, wherein in step a) the electrolysis is carried out for a total charge between 2 F / mol and 30 F / mol, preferably between 2 F / mol and 15 F / mol .

15. The process according to any one of the preceding claims, wherein in step a) the cathode is made of a material selected from silver, graphite (C) , vitreous carbon (GC) , preferably reticulatedvitreous carbon (RVC) or reticulated vitreous carbon foam (RVC foam) , nickel, preferably nickel foam, stainless steel, aluminium, platinum, gold, cobalt, titanium, copper, lead, tungsten, bronze lead, and tin; preferably the cathode is made of silver or glassy carbon (GC) .

16. The process according to any one of the preceding claims, wherein the anode is made of a material selected from graphite (C) , vitreous carbon (GC) , preferably reticulated vitreous carbon (RVC) or reticulated vitreous carbon foam (RVC foam) , nickel, preferably nickel foam, stainless steel, aluminium, platinum, gold, cobalt, titanium, copper, lead, tungsten, bronze lead, and tin; preferably the anode is made of graphite or glassy carbon (GC) .

17. The process according to any one of the preceding claims, wherein in step a) the electrolysis is carried out in a flow reactor, by continuous feeding of a reaction mixture and carbon dioxide.

18. The process according to claim 17, wherein in step a) the flow reactor is selected from plug-flow reactor, chip-flow reactor, continuous stirred tank reactor (CSTR) .

19. The process according to any one of the preceding claims, wherein in step a) the electrolysis is carried out by immersing the electrochemical cell in an ultrasonic bath, preferably the ultrasound frequency is between 40 kHz and 130 kHz.

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