Manufacture of polyhydroxylamine via electrolysis of substrates

Abstract

The invention relates to process for manufacturing a C3-C6-polyhydroxylamine by reacting a C3-C6-polyhydroxylaldehyde or a C3-C6-polyhydroxylketone with hydroxylamine or ions thereof, or with ammonia or ions thereof, and by subsequently electrolyzing the solution obtained in the previous step.

Description

[0001] MANUFACTURE OF POLYHYDROXYLAMINE VIA ELECTROLYSIS OF SUBSTRATES

[0002] Technical field

[0003] The invention relates to a process for manufacturing a Cs-Ce-polyhydroxylamine, such as isoserinol, serinol or glucamine, via electrochemical reduction of the products obtained by reacting a Cs-Ce-polyhydroxylaldehyde or a Cs-Ce-polyhydroxylketone with hydroxylamine or ions thereof, or ammonia or ions thereof.

[0004] Background art

[0005] Polyhydroxylamines, such as isoserinol, serinol and glucamine, are very versatile compounds that can be used as substrates or reactants for several synthetic processes.

[0006] One of the most frequent preparations of polyhydroxylamines is based on the catalytic reductive alkylation of ammonia with polyhydroxylated carbonyl substrates, such as with monosaccharides, and alternatively, by catalytic hydrogenation with molecular hydrogen of the respective oximes, hydrazones, or phenylhydrazones. The use of hydrogen gas under high pressure and temperature, however, shows significant functional group incompatibility, as well as being possibly dangerous and difficult to handle. As an alternative, metal hydride reducing agents can be employed, though the selective formation of primary amines under these conditions is challenging. Moreover, metal hydride reducing agents are typically harsh chemicals, in that they are harmful for the environment.

[0007] Polyhydroxylamines have been previously prepared also via electrochemical methods.

[0008] Fedorohko, M. et al., Chem. Pap. 1994, 48, 274-277, discloses the electrochemical synthesis of several glycamines, such as of glucamine, by electroreductive amination via oxime formation and with a mercury cathode. Notably, this article discloses that the product characterization was carried out only by measuring the melting point of the obtained glycamines. In some cases, for example for glucamine, the melting point reported in this article does not coincide accurately with the reported melting point for pure D-glucamine (as e.g. reported in Wayne, W. et a / ., Am. Chem. Soc., 1940, 62 (12), 3314-3316), suggesting that the glycamines obtained according to this paper are not pure, and thus that the reported yields are not correct. Moreover, it has been found that following the electrochemical synthesis protocol disclosed in this document with a cathode different than mercury and a different anolyte does not provide the desired product D-glucamine, whereby mercury cathode seems essential for these kinds of substrates and products.

[0009] Fedorohko, M. et al., Chem. Pap. 1989, 43 (2), 335-341, discloses the electrolysis of serinol with a mercury pool cathode starting from the corresponding oxime. This document further discloses a side reaction occurring during the electrolysis, consisting in the electroreductive cleavage of the hydroxyl groups of the l,3-dihydroxy-2-propanone-oxime, producing the by-products 2-aminopropane and 2-amino-l-propanol, together with the desired product serinol.

[0010] Ryan, G. et al., Tetrahedron Lett. 1988, 29 (30), 3699-3702, discloses the electrochemical synthesis of glucamine by electroreductive amination via oxime formation, and with a mercury pool cathode. The reported reduction yield of glucamine is 9%.

[0011] Thus, the electrochemical manufacture of polyhydroxyamines is conventionally carried out using mercury as a working cathode, which could be particularly advantageous from an effectiveness point of view, however it is highly toxic.

[0012] In view of the above, there is the need to provide processes for the manufacture of polyhydroxylamines that are safe for both users and the environment, and at the same time that provide suitable yields.

[0013] Summary of the invention

[0014] The invention relates to a process as set out in claim 1.

[0015] The process of the invention advantageously allows to obtain Cs-Ce-polyhydroxylamine in suitable yields, and using cathodes that are less toxic compared to the ones used in the prior art.

[0016] Embodiments of the invention are set out in the dependent claims and in the detailed description of the invention.

[0017] Detailed description of the invention

[0018] In a first aspect, the invention relates to a process for manufacturing a Cs-Ce- polyhydroxylamine comprising the following steps: a) providing an electrolyte solution comprising : i. a Cs-Ce-polyhydroxylaldehyde or a Cs-Ce-polyhydroxylketone; and ii. hydroxylamine or ions thereof, or ammonia or ions thereof; b) reacting the Cs-Ce-polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone with hydroxylamine or ions thereof, or with ammonia or ions thereof; c) electrolyzing the electrolyte solution obtained in step b) to obtain the C3-C6- polyhydroxylamine; wherein, the cathode is based on a material that has an exchange current density (jo / A cm-2) lower than IO-6, such as lower than IO-7, provided that the cathode is not mercury-based; and wherein the pH during step c) is maintained : at 10 or lower, preferably at 9 or lower, more preferably at 8 or lower, when the electrolyte solution of step a) comprises hydroxylamine or ions thereof, and at 11 or lower, preferably at 10 or lower, when the electrolyte solution of step a) comprises ammonia or ions thereof. Preferably, the electrolyte solution is selected from the group consisting of aqueous solution, lower alcohol, and mixtures thereof. Moreover, according to a preferred embodiment, the cathode is based on an element selected from the group consisting of zinc, silver, tantalum, tungsten, molybdenum, tin, lead, titanium, and mixtures thereof; more preferably of zinc, lead, titanium, and mixtures thereof, and even more preferably of lead, titanium, and mixtures thereof.

[0019] The process of the invention provides an effective way to manufacture C3-C6- polyhydroxylamine, such as isoserinol, serinol and glucamine, via electrochemical reduction (step c)) of a corresponding substrate, namely the substrate that is obtained by reacting the Cs-Ce-polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone with hydroxylamine or ions thereof, or with ammonia or ions thereof, according to step b). Accordingly, the process of the invention does not require the use of harsh chemicals or of dangerous means, such as metal hydride reducing agents or high pressure H2. Moreover, the process of the invention disposes the need of using cathodes that are highly toxic to effectively manufacture the C3- Ce-polyhydroxylamine. In view of this, the process of the invention can be considered safe for both users and the environment. The choice of the cathode has been found very important for the effectiveness of the process, as the Cs-Ce-polyhydroxylamine is electrochemically manufactured at the cathode.

[0020] Furthermore, the process of the invention is highly reproducible, and provides suitable yields without using harsh chemicals or dangerous means. Indeed, the process of the invention provides for a yield of the electrolyzation step c) of 15% or more, preferably of 20% or more, more preferably of 30% or more, even more preferably of 35% or more, and most preferably of 40% or more.

[0021] The exchange current density (jo I A. cm-2) of the cathode should be measured by means known in the art, for example as disclosed in S. Trasatti, Electrocatalysis of Hydrogen Evolution : Progress in Cathode Activation, in: Adv. Electrochem. Sci. Eng., John Wiley & Sons, Ltd, 1991.

[0022] As used herein, the term "material-based" or "based on a material" when referring to any of the electrodes, that is to the cathode or the anode, means an electrode, e.g. the cathode or the anode, containing that material or element (e.g. lead, titanium, platinum, etc.) which, in use ( / .e. during step c)), is exposed to the electrolyte solution.

[0023] As used herein, the term "polyhydroxylamine" refers to a straight or branched hydrocarbon chain, wherein at least two hydrogen atoms are replaced by hydroxyl groups, and one hydrogen atom is replaced by an amine group, preferably a primary amine group. In particular, "Cs-Ce-polyhydroxylamine" refers to a polyhydroxylamine as above defined, wherein the hydrocarbon chain contains from 3 to 6 carbon atoms. Suitable examples of C3- Ce-polyhydroxylamine include 2-amino-l,3-propanediol (serinol), 3-amino-l,2-propanediol (isoserinol), and amino-sugars, such as 1-amino-l-deoxy-D-glucitol (glucamine), 1-amino-l- deoxy-arabinitol, 1-amino-l-deoxy-xylitol, 1-amino-l-deoxy-ribitol, 1-amino-l-deoxy- galactitol, and 1-amino-l-deoxy-mannitol; preferably, the amino-sugars being in their most common naturally occurring form, that is D-glucamine, 1-amino-l-deoxy-D-arabinitol, 1- amino-l-deoxy-L-arabinitol, 1-amino-l-deoxy-D-xylitol, 1-amino-l-deoxy-D-ribitol, 1- amino-l-deoxy-D-galactitol, and 1-amino-l-deoxy-D-mannitol. According to a preferred embodiment, the Cs-Ce-polyhydroxylamine is isoserinol, serinol or glucamine, preferably serinol or glucamine, and more preferably serinol or D-glucamine.

[0024] As used herein, the terms "polyhydroxylaldehyde" and "polyhydroxylketone" refers to a straight or branched hydrocarbon chain, wherein at least two hydrogen atoms are replaced by hydroxyl groups, and two hydrogen atoms are replaced by, respectively, an aldehyde group and a ketone group. One or more hydroxyl groups can be linked to one or more protecting groups, such as alkyl groups, carboxylate groups, and silyl groups. These protecting groups, particularly the alkyl and carboxylate groups, may include aliphatic units and / or aromatic rings, thereby providing one or more alkoxy groups or esters (respectively). The protecting groups, e.g. the alkyl groups, will be removed after step c), thereby providing the desired Cs-Ce-polyhydroxylamine, and indeed they serve as protecting groups, possibly protecting the hydroxyl groups from the electroreduction of step c). In particular, "C3-C6- polyhydroxylaldehyde" or "Cs-Ce-polyhydroxylketone" refers to a polyhydroxylaldehyde or polyhydroxylketone as above defined, wherein the hydrocarbon chain contains from 3 to 6 carbon atoms. Suitable examples of Cs-Ce-polyhydroxylaldehyde include Cs-Ce-aldose, such as glyceraldehyde, erythrose, threose, ribose, arabinose, xylose, lyxose, glucose, mannose, and galactose; preferably in their most common naturally occurring form. Suitable examples of Cs-Ce-polyhydroxylketone include Cs-Ce-ketose, such as dihydroxyacetone, erythrulose, ribulose, xylulose, fructose, psicose, sorbose, and tagatose; preferably in their most common naturally occurring form. According to a preferred embodiment, the polyhydroxylaldehyde is glyceraldehyde or glucose, preferably D-glucose, and the polyhydroxylketone is dihydroxyacetone, or 2-phenyl-l,3-dioxan-5-one according to the embodiment wherein one or more hydroxyl groups of the polyhydroxylketone are linked to one or more alkyl groups.

[0025] As used herein, the term "aqueous solution" refers to solutions wherein water is the solvent.

[0026] As used herein, the term "lower alcohol", when referring to the electrolyte solution, refers to solutions wherein the solvent is one or more Ci-C4-alcohol, such as methanol; ethanol; n- and / -propyl alcohol; n-, / '-, sec-, and t-butyl alcohol; and mixtures thereof. According to a preferred embodiment, the lower alcohol is selected from methanol, ethanol, and mixtures thereof.

[0027] Step c) provides for converting the substrate obtained by the reaction of step b) to the Cs-Ce-polyhydroxylamine of interest. Accordingly, the starting reagent, namely the polyhydroxylaldehyde or the polyhydroxylketone, comprised within the electrolyte solution, is the compound that has the same structure as the polyhydroxylamine, but with a carbonyl group, such as an aldehyde or ketone group, instead of the amine group. By way of example, the starting reagent, i.e. the polyhydroxylketone, of the polyhydroxylamine serinol is the following:

[0028] Dihydroxyacetone Serinol

[0029] Poly hydroxyl ketone Polyhydroxylamine whereas the starting reagent, i.e. the polyhydroxylaldehyde, of the polyhydroxylamine glucamine is the following:

[0030] Glucose Glucamine

[0031] Poly hydroxylaldehyde Polyhydroxylamine

[0032] When the one or more hydroxyl groups of the Cs-Ce-polyhydroxylaldehyde or C3-C6- polyhydroxylketone are linked to one or more protecting groups, such as alkyl groups, thereby providing one or more alkoxy groups, the process of the invention can provide a further step d) after step c), that is removing the one or more protecting groups, such as alkyl groups, to provide the desired Cs-Ce-polyhydroxylamine. Step d) can be carried out according to means known in the art, for example by acidifying a solution containing the product of step c); according to this embodiment, a possible Cs-Ce-polyhydroxylketone having two hydroxyl groups linked to the protecting alkyl groups is 2-phenyl-l,3-dioxan-5-one:

[0033] 2-Phenyl-l,3-dioxan-5-one

[0034] According to the embodiment above, providing an electrolyte solution comprising 2- phenyl-l,3-dioxan-5-one with hydroxylamine or ions thereof according to step a), then reacting the two components according to step b), then electrolyzing the electrolyte solution according to step c), and finally removing the one or more protecting alkyl groups according to step d), e.g. by acidifying the solution comprising the product of step c), allows manufacturing the desired Cs-polyhydroxylamine serinol in suitable yields.

[0035] Step a) provides for providing an electrolyte solution comprising at least the following two components: i. a Cs-Ce-polyhydroxylaldehyde or a Cs-Ce-polyhydroxylketone; and ii. either a hydroxylamine or ions thereof (that is, hydroxylammonium), or ammonia or ions thereof (that is, ammonium).

[0036] These two components react in the following step b) to provide a substrate that later is subjected to the electrolysis reaction, thereby providing the desired Cs-Ce-polyhydroxylamine.

[0037] Ions of hydroxylamine, namely hydroxylammonium, or of ammonia, namely ammonium, can be conveniently added to the electrolyte solution by addition of a hydroxylammonium salt, such as hydroxylamine hydrochloride, or of an ammonium salt.

[0038] The process of the invention provides for manufacturing a Cs-Ce-polyhydroxylamine by reacting a Cs-Ce-polyhydroxylaldehyde or a Cs-Ce-polyhydroxylketone according to step b), and then by converting the reaction products via the electrolyzation step c). According to a preferred embodiment, the Cs-Ce-polyhydroxylamine is manufactured by reacting the Cs-Ce- polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone with hydroxylamine or ions thereof under step b).

[0039] According to a preferred embodiment, the Cs-Ce-polyhydroxylamine comprises a primary amine. Furthermore, hydroxyl groups comprised within the Cs-Ce-polyhydroxylamine are preferably not geminal, i.e. are vicinal and / or isolated. Moreover, according to a preferred embodiment, the Cs-Ce-polyhydroxylamine has a straight hydrocarbon chain. By way of example, a preferred Cs-polyhydroxylamine according to these features is serinol or isoserinol, and a preferred Ce-polyhydroxylamine according to these features is glucamine, preferably D-glucamine.

[0040] According to a further preferred embodiment, the Cs-Ce-polyhydroxylamine has the following formula (I):

[0041] Formula (I) wherein : n is an integer number from 0 to 3, and

[0042] R1, R2, R3, and R are independently selected from the group consisting of hydrogen, hydroxyl group (-OH), and primary amine group (-NH2), provided that at least two among R1, R2, R3, and R are hydroxyl groups (-OH), and only one among R1, R2, R3, and R is a primary amine group (-NH2). According to this embodiment, the Cs-Ce-polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone is preferably the compound of formula (I) wherein the carbon bonding the primary amine group in formula (I) forms a double bond with oxygen instead of bonding the primary amine group, thereby providing a carbonyl group (-C(O)-), such as an aldehyde group or a ketone group.

[0043] According to another preferred embodiment, the Cs-Ce-polyhydroxylaldehyde or the C3- Ce-polyhydroxylketone has the following formula (I)':

[0044] Formula (I)' wherein : n is an integer number from 0 to 3, and

[0045] R1, R2, R3, and R' are independently selected from the group consisting of hydrogen, hydroxyl group (-OH), alkoxy group, alkyl-ester, alkyl-silyl group, and the oxygen of the aldehyde group or the ketone group; preferably selected from the group consisting of hydrogen, hydroxyl group (-OH), and the oxygen of the aldehyde group or the ketone group; provided that at least two among R1', R2', R3', and R' are hydroxyl groups (-OH) and / or alkoxy groups, and only one among R1', R2', R3', and R' is the oxygen of the aldehyde group or the ketone group.

[0046] According to a preferred embodiment, the Cs-Ce-polyhydroxylamine is serinol, i.e. the compound of formula (IIA):

[0047] Formula (IIA), Serinol and the Cs-Ce-polyhydroxylketone is dihydroxyacetone, i.e. the compound having formula (IIB):

[0048] Formula (IIB), Dihydroxyacetone.

[0049] According to another preferred embodiment, the Cs-Ce-polyhydroxylamine is glucamine, i.e. the compound of formula (IIIA), preferably D-glucamine:

[0050] Formula (IIIA), Glucamine and the Cs-Ce-polyhydroxylaldehyde is glucose, i.e. the compound having formula (IIIB), preferably D-glucose:

[0051] Formula (IIIB), Glucose.

[0052] According to a further preferred embodiment, the Cs-Ce-polyhydroxylamine is isoserinol, i.e. the compound of formula (IVA):

[0053] OH

[0054] HO^^L^^NH2

[0055] Formula (IVA), Isoserinol and the Cs-Ce-polyhydroxylketone is glyceraldehyde, i.e. the compound having formula (IVB):

[0056] Formula (IVB), Glyceraldehyde.

[0057] At least step c) is carried out within an electrolytic cell. The electrolytic cell to carry out the step c) can be either divided or undivided. Preferably, step c) is carried out within an electrolytic cell formed by two-compartments divided by a permeable separator (divided electrolytic cell), such as a cation exchange membrane or a porous septum. The divided electrolytic cell improves the reproducibility of step c). When step c) is carried out in a divided electrolytic cell, the electrolyte solution is the catholyte solution, i.e. the solution present within the cathodic compartment of the divided electrolytic cell. As mentioned above, the electrolyte solution, preferably the catholyte solution (when a divided electrolytic cell is used), is selected from the group consisting of aqueous solution, lower alcohol, and mixtures thereof. According to a preferred embodiment, the electrolyte solution is selected from the group consisting of aqueous solution; methanol; ethanol; n- and / -propyl alcohol; n-, / '-, sec-, and t-butyl alcohol; and mixtures thereof; and more preferably is selected from the group consisting of aqueous solution; methanol; ethanol; and mixtures thereof. These electrolyte solutions have been found to provide an effective electrochemical reduction when the cathodes mentioned above are used. Moreover, these electrolyte solutions are also generally safe for both users and the environment, and are also advantageously readily available.

[0058] When a divided electrolytic cell is used, the composition of the anolyte solution (that is, the solution present in the anodic compartment of the divided electrolytic cell) may vary, and can be selected according to conventional and standard knowledge in the art based on several factors, such as on the Cs-Ce-polyhydroxylamine to be manufactured, and on the composition of the catholyte solution. According to a preferred embodiment, the anolyte solution can be selected from the group consisting of an aqueous solution, lower alcohol, and mixtures thereof; more preferably can be selected from the group consisting of aqueous solution; methanol; ethanol; n- and / -propyl alcohol; n-, / '-, sec-, and t-butyl alcohol; and mixtures thereof; and even more preferably can be selected from the group consisting of aqueous solution; methanol; ethanol; and mixtures thereof.

[0059] The electrolyte solution can further comprise other components, such as acids, acid salts, and / or buffers. One or more of these further components can be provided within the electrolyte solution from the start of the process of the invention, i.e. from step a), and / or can be added after step a), e.g. after the reaction of step b), that is before the electrolyzation step c), so that to bring and / or maintain the pH of the electrolyzation in the ranges herein discussed.

[0060] According to a preferred embodiment, the reaction of step b) is carried out by reacting the Cs-Ce-polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone with a stoichiometric amount or a molar excess of the hydroxylamine or ions thereof (that is, hydroxylammonium), for example a molar excess of 1.5 or higher, preferably of 2.0 or higher, more preferably of 2.3 or higher, and even more preferably of 2.5 or higher. In general, step b) is carried out by reacting Cs-Ce-polyhydroxylaldehyde or Cs-Ce-polyhydroxylketone with hydroxylamine or ions thereof in a molar ratio that can be of 5: 1 to 1 : 10, preferably of 3: 1 to 1:5, more preferably of 3: 1 to 1:3, even more preferably of 1: 1 to 1:3, and most preferably of 1:2 to 1:2.6.

[0061] According to a preferred embodiment, the reaction of step b) is carried out by reacting the Cs-Ce-polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone with a stoichiometric amount or a molar excess of ammonia or ions thereof (that is, ammonium), for example a molar excess of 3 or higher, preferably of 5 or higher, more preferably of 10 or higher, and even more preferably of 13 or higher. In general, step b) is carried out by reacting C3-C6- polyhydroxylaldehyde or Cs-Ce-polyhydroxylketone with ammonia or ions thereof in a molar ratio that can be of 3: 1 to 1:30, preferably of 2: 1 to 1:20, more preferably of 1 : 1 to 1 :20, even more preferably of 1:5 to 1: 15, and most preferably of 1 : 10 to 1: 15.

[0062] According to a preferred embodiment, the reaction of step b) can be carried out at room temperature (that is, 25 °C), in particular when hydroxylamine or ions thereof are comprised within the reaction mixture, or by heating the reaction mixture, for example at a temperature of 100 °C or below, preferably of 90 °C or below, more preferably of 80 °C or below, even more preferably of 50 to 80 °C, and most preferably of 60 to 70 °C.

[0063] The reaction of step b) can provide an oxime as product, in particular when hydroxylamine or ions thereof are reacted with the Cs-Ce-polyhydroxylaldehyde or the C3-C6- polyhydroxylketone, or an imine as product, in particular when ammonia or ions thereof are reacted with the Cs-Ce-polyhydroxylaldehyde or the Cs-Ce-polyhydroxylketone. The oxime or the imine may be in equilibrium with further reaction products, such as, but not limited to, the dimeric form of the oxime or of the imine, depending e.g. on the reaction solvent and on the pH of the same. At least the oxime or the imine will be subjected to the electrochemical reduction via the electrolysis step c), thereby providing the desired Cs-Ce-polyhydroxylamine.

[0064] After the reaction of step b), and before the electrolyzation step c), further steps can be carried out, such as for example dilute the electrolyte solution obtained in step b) and / or adding one or more further components to the electrolyte solution obtained in step b), such as at least an acid and / or at least an acid salt and / or at least a buffer.

[0065] The pH of step c) is maintained at 10 or lower, more preferably at 9 or lower, even more preferably at 8 or lower, when the electrolyte solution of step a) comprises hydroxylamine or ions thereof; when the product to manufacture is a Ce-polyhydroxylamine, such as glucamine, the pH of step c) is maintained at 9 or lower, preferably at 8 or lower. According to a preferred embodiment, when the electrolyte solution of step a) comprises hydroxylamine or ions thereof, e.g. when the product to manufacture is a Ce-polyhydroxylamine, such as glucamine, step c) is maintained at a pH of 1 to 9, preferably of 4 to 9, more preferably of 4 to 8, and even more preferably of 4 to 7, such as of 6 to 6.5. According to another preferred embodiment, when the electrolyte solution of step a) comprises hydroxylamine or ions thereof, e.g. when the product to manufacture is a Cs-polyhydroxylamine, such as serinol, step c) is maintained at a pH of 4 to 10, preferably of 4 to 10, more preferably of 4 to 9, even more preferably of 4 to 8, and most preferably at 4 to 7, such as of 6 to 6.5. It has been found that, when the electrolyte solution of step a) comprises ammonia or ions thereof, the pH of step c) can be maintained slightly more basic compared to the pH when solution of step a) comprises hydroxylamine or ions thereof; accordingly, the pH of step c) is maintained at 11 or lower, preferably at 10 or lower, when the electrolyte solution of step a) comprises ammonia or ions thereof. According to a preferred embodiment, when the electrolyte solution of step a) comprises ammonia or ions thereof, step c) is maintained at a pH of 1 to 11, preferably of 1 to 10, more preferably of 4 to 10, even more preferably of 6 to 10, and most preferably of 7 or 8 to 10. It has also been found that, operating at very low pH, such as of pH lower than 1 (or lower than 3 when the product to be manufactured is a C3- polyhydroxylamine such as serinol), might promote the cleavage of some of the hydroxyl groups of the polyhydroxylaldehyde or polyhydroxylketone, and / or hydrolysis reactions of the electrolysis intermediates, thereby generating by-products. As known according to the general knowledge in the field, when the electrolyte solution is not an aqueous solution e.g. when the electrolyte solution is a lower alcohol or a mixture thereof, the pH measurement might have a certain approximation due to the nature of the medium, e.g. an approximation of about ±1. Since the electrolysation step c) occurs at the cathode, when a divided electrolytic cell is used, the pH should be maintained in the ranges provided above at least in the solution within the cathodic compartment, that is at the catholyte.

[0066] According to an embodiment, at least during step c), the electrolyte solution, preferably both the catholyte and anolyte solutions (when a divided electrolytic cell is used), is kept under stirring, for example by conventional means, such as magnetic stirring or stirring via a mechanical pump.

[0067] The pH during the electrolysis step c) can be maintained within the ranges mentioned above thanks to the addition of suitable acids, acid salts, and / or buffers to the electrolyte solution, preferably to the catholyte solution and / or to the anolyte solution (when a divided electrolytic cell is used). Thus, the electrolyte solution, preferably the catholyte solution and / or the anolyte solution (when a divided electrolytic cell is used), can comprise at least an acid, such as inorganic acid, e.g. nitric acid, orthophosphoric acid, sulfuric acid, and perchloric acid, and / or at least an acid salt, and / or at least a buffer, such as phthalate buffer, succinate buffer, citrate buffer, phosphate buffer, and acetate buffer; for example in an amount of 0.1 M or higher, preferably of 0.5 M or higher. When a divided electrolytic cell is used, the anolyte solution preferably comprises at least an acid, such as inorganic acid, e.g. nitric acid, orthophosphoric acid, sulfuric acid, and perchloric acid, and / or at least an acid salt, for example in an amount of 0.1 M or higher, or of 0.2 M or higher, or even of 0.5 M or higher, e.g. 0.6 M or higher, such as of 1.0 M or higher; alternatively, or in addition to the anolyte comprising the components mentioned above, the catholyte solution preferably comprises a buffer, e.g. phthalate buffer, succinate buffer, citrate buffer, phosphate buffer, and acetate buffer; such buffers being preferably present in an amount of 0.1 M or higher, more preferably of 0.5 M or higher. As referred herein, acid salts are salts producing protons (H+) after being dissolved in a solvent, and can be e.g. sodium hydrogen sulfate, sodium dihydrogen phosphate, and disodium hydrogen phosphate, preferably present in an amount of 0.1 M or higher, preferably 0.5 M or higher. According to an embodiment, the at least an acid and / or at least an acid salt and / or at least a buffer can be added before step c) to the electrolyte solution, preferably to the catholyte solution and / or to the anolyte solution (when a divided electrolytic cell is used). Accordingly, the electrolyte solution, preferably the catholyte solution and / or the anolyte solution (when a divided electrolytic cell is used), comprises said acid, acid salt, and / or buffer at least during step c).

[0068] Moreover, it has been found that, when a divided cell is used, it can be advantageous that the concentration of protons (H+) within the anolyte is equal or higher compared to the concentration of protons within the catholyte, particularly when the electrolyte solution of step a) comprises hydroxylamine or ions thereof and when a Cs-polyhydroxylamine has to be manufactured, such as serinol. Indeed, as showed in the experimental part, if the concentration of the acids, acid salts, and / or buffers of the anolyte is lower than the one of the catholyte, the electroreduction of step c) might not occur, particularly when a C3- polyhydroxylamine such as serinol has to be manufactured. According to a preferred embodiment, in particular when the electrolyte solution of step a) comprises hydroxylamine or ions thereof, the concentration of protons within the anolyte is higher than 0.5 M, preferably is 0.6 M or higher, and such concentration of protons within the anolyte is equal or higher compared to the concentration of protons within the catholyte. This embodiment has been found particularly advantageous to effectively manufacture the product, in that it allows protons to move from the anolyte to the catholyte during electrolysis (thanks both to migration and to diffusion due to the chemical concentration gradient), and at the same time it can generate a suitable environment for the electroreduction of step c) to occur (particularly, a suitable environment in terms of pH at the catholyte) while generating low amounts of by-product (e.g. cleavage by-products).

[0069] As mentioned above, the electrolyte solution, preferably the catholyte solution (when a divided electrolytic cell is used), comprises the Cs-Ce-polyhydroxylaldehyde or the C3-C6- polyhydroxylketone and the hydroxylamine or ions thereof, or ammonia or ions thereof, to be reacted according to step b) and then converted to the Cs-Ce-polyhydroxylamine according to step c).

[0070] According to an embodiment, all steps a) to c) are carried out directly within the electrolytic cell, preferably within the cathodic compartment (when a divided electrolytic cell is used). According to another embodiment, only step c) is carried out within the electrolytic cell, preferably within the cathodic compartment (when a divided electrolytic cell is used).

[0071] The amount of the reaction product of step b), such as of e.g. the oxime or the imine, within the electrolyte solution, preferably within the catholyte solution (when a divided electrolytic cell is used), can be preferably of 0.01 to 10 M, more preferably of 0.01 to 1 M, even more preferably of 0.05 to 0.5 M, and most preferably of 0.1 and 0.2 M, such as of 0.1 M. Such amounts have been found as providing suitable yields of step c), as well as a suitable recovery of the product via e.g. crystallization, particularly for the amounts of 0.1 and 0.2 M, and more particularly for 0.1 M. In case the solution comprises the oxime and further forms thereof (e.g. dimeric), the concentrations herein provided refers to the concentration of the monomeric form of the oxime. In case the solution comprises the imine and further forms thereof (e.g. dimeric), the concentrations herein provided refers to the concentration of the monomeric form of the imine.

[0072] According to a preferred embodiment, before step c), the cathode is treated with an acidic solution, such as a solution of an inorganic acid, for example with a concentration of 0.01 M to 1 M, preferably of 0.05 to 0.5 M, and more preferably of 0.1 M. Suitable inorganic acids include halo-acid, such as HCI and HBr. This treatment has been found to remove the oxidation layer that could be formed on the surface of the cathode, thereby improving the effectiveness of step c).

[0073] According to an embodiment, step c) can be carried out using a counter electrode, i.e. an anode, based on a metal selected from those typically used in similar electrochemical systems, such as platinum-based or based on conductive oxides, such as oxides of titanium, tantalum, iridium, ruthenium, tin, or mixtures thereof. The reference electrode can be selected from those typically used in similar electrochemical systems, and can be for example silver-based, e.g. a silver foil (pseudo-reference electrode) or Ag / AgCI (3 M KCI).

[0074] Step c) of the invention can be performed in galvanostatic mode or in potentiostatic mode. When step c) is performed in galvanostatic mode, the galvanostatic conditions may vary, and can depend on e.g. surface of the cathode in contact with the catholyte; for example, the current density can be of -0.001 A / cm2to -1 A / cm2, and may vary depending on the electrolyte (the catholyte, when a divided cell is used) selected; for example, the current density can be of -0.01 A / cm2to -0.2 A / cm2. For example, when the electrolyte solution (e.g. the catholyte) is a lower alcohol, such as methanol or ethanol, the current density can range between -0.01 A / cm2to -0.08 A / cm2; and between -0.04 A / cm2to -0.15 A / cm2when the electrolyte solution (e.g. the catholyte) is an aqueous solution. When step c) is performed in potentiostatic mode, the potentiostatic conditions may vary, and can depend on e.g. the catholyte and anolyte solutions; for example, the constant potential can be of -0.5 V or more cathodic (meaning from -0.5 V to more negative values), preferably of -1.0 V or more cathodic, more preferably of -1.5 V or more cathodic, even more preferably of -2.0 V or more cathodic, and most preferably of -2.5 V or more cathodic, e.g. of -2.5 V to -3.5 V, vs. the reference electrode, such as the silver / silver chloride (1 or 3 M KCI) reference electrode or a silver-based (Ag) pseudo-reference electrode.

[0075] The total quantity of charge and the time to carry out step c) can vary, for example based on the combination of the current density applied and the cathode surface employed, as well as on the amount of substrate(s) to be reduced, its purity, etc. Accordingly, the optimal conditions of quantity of charge and time to carry out step c) can be selected according to conventional and standard knowledge in the art, as well as by using ordinary analytical means to detect the completion of the reaction, such as spectrometric equipment or spectroscopic techniques, e.g. HPLC, or (quantitative) Nuclear Magnetic Resonance ((q)NMR) analysis.

[0076] Step c) can be advantageously carried out at room temperature, i.e. 25 °C. Moreover, step c) can be carried out without controlling the temperature of the reaction, whereby a temperature increase might occur without affecting the effectiveness of the reaction.

[0077] Experimental section

[0078] Material and methods

[0079] Reactants and / or solvents employed in the following Examples are known and readily available (e.g. commercially available); if not, they may be prepared according to known methods in literature or as set out in the Examples.

[0080] All of the pH values of the following Examples were measured using the pHmeter: Amel 2335, with Electrode: pH combined glass electrode 411 / CGG / 12.

[0081] TheXH-NMR and13C-NMR spectra were acquired at 400.13 MHz and 100.61 MHz, respectively, on a Bruker Advance 400 NEO spectrometer equipped with a TOPSPIN software package and probe "BBI 400 MHz SI" with Z gradient.13C signal multiplicities were based on attached proton test experiments (APT). Chemical shifts are given in ppm (6) and are referenced to solvent signal. D2O (6H D2O 4.79 ppm). DMSO (6H DMSO 2.5 ppm).13C-NMR spectra were acquired in D2O solvent using tetramethylsilane (TMS) as external standard (6Me 0.00 ppm).

[0082] For the ESI-MS analysis, the HR-MS instrument Q-ToF Synapt G2-S / (Waters, Milford, MA, USA) was used. Data were processed with a MassLynxTM v4.2 software (Waters). Furthermore, the following conditions were used for ESI-MS analysis:

[0083] • Source type: Electrospray ionization (ESI)

[0084] • Source conditions:

[0085] - Positive polarity

[0086] - Capillary voltage 1.0-3.0 kV

[0087] - Sampling cone 60-80

[0088] - Source heater temperature 120°C

[0089] - Desolvatation temperature 150°C

[0090] - Desolvatation gas flow rate 600 L / h

[0091] • High Resolution Mode

[0092] • Acquisition range 50-450 m / z

[0093] • Leucine enkephalin (Waters) was used as a lock-mass compound.

[0094] Unless specified otherwise, concentrations of the oximes mentioned in these examples refer to the concentration of the monomeric form of the oximes. Example 1 - Reaction of the Ce-polyhydroxylaldehyde D-glucose with hydroxylamine or ions thereof (step b))

[0095] Hydroxylamine hydrochloride (6.461 g, 0.0930 mol, 2.5 eq) was dissolved in dry MeOH (40 mL). Two drops of phenolphthalein (1% solution in EtOH) were added. A solution of sodium methoxide (5.124 g, 0.0948 mol, 2.55 eq) in dry MeOH (17 mL) was added slowly to the solution, upon which a white precipitate was formed. Addition of the base was halted when the mixture stayed pink for approximately one minute. The mixture was stirred for 40 minutes and filtered to remove salts. The filtrate was heated to 70 °C, and D-glucose (6.7 g, 0.0372 mol, 1 eq) was added in small portions. The mixture was stirred at 70 °C for 1.7 h, then cooled to room temperature and stirred for 12 hours. An aliquot of the solution (3 mL) was concentrated to obtain a sample of the reaction product forXH,13C-NMR and ESI-MS analyses, confirming the presence of the oxime product, while the remaining part was used, without isolation, for the further electrolysis step.XH-NMR (400 MHz; D2O): 6 7.53 (d, J = 7 Hz, 1H), 4.40 (t, J = 7.0 Hz, 1H), 3.96 (dd, J = 7.3, 1.4 Hz, 1H), 3.84 (dd, J = 11.7, 3.0 Hz, 1H), 3.76 (td, J = 5.8, 3.0 Hz, 1H), 3.64 (dd, J = 11.7, 6.2 Hz, 1H), 3.58 (dd, J = 8.5, 1.5 Hz, 1H).13C NMR (101 MHz, D2O): 6 151.37, 70.90, 70.88, 70.34, 69.91, 62.87. ESI-MS [M- H]’: m / z calcd for [CeHisNOe - H]’ 194.0743, obsd 194.11. ESI-MS [M + H]+: m / z calcd for [C6Hi3NO6+ H]+196.0743 , obsd 218.13 [M + Na]+

[0096] Example 2 - Manufacturing of the Ce-polyhydroxylamine D-glucamine via electrolyzation of the solution of Example 1 (step c))

[0097] Trial A

[0098] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead (Pb) as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pretreated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution (20.45 mL) was a solution of 0.1 M tetrabutylammonium perchlorate (NBU4CIO4) in methanol. An aliquot (4.55 mL of oxime solution 0.55 M) of the solution obtained according to Example 1 was added to the catholyte solution to obtain a concentration of 0.1 M of D-glucose oxime (25 mL catholyte final volume). The anolyte (25 mL) was a solution of 1.7 M perchloric acid in methanol. The reaction was conducted stirring at 25 °C, even if an increase of temperature was observed during the electroreduction due to heat dissipation which occurred during the electrolysis process (observed also in the following Trials). A constant potential of -3.5 V vs. the Ag pseudoreference electrode was applied, and the solution was regularly sampled for pH measurements (showing a pH decrease from 8 to 1) and NMR analysis. Total charge was 2908 C, total electrolysis time was 5.7 h, and pH measured at the end of the electrolysis was 1. Current density increased during the electrolysis from -0.0472 to -0.1389 A / cm2. Estimated yield with qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 20.3% Trial B

[0099] The same conditions as Example 2, Trial A were used, but for the catholyte solution the present Trial B used 0.1 M sodium perchlorate instead of 0.1 M tetrabutylammonium perchlorate. Total charge was 3789 C, total electrolysis time was 6.7 h, and pH measured at the end of the electrolysis was 1. Estimated yield with qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 17.5%.

[0100] Trial C

[0101] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M acetate buffer in MeOH (20.45 mL) of pH 6. An aliquot of the solution obtained according to Example 1 (4.55 mL of oxime solution 0.55 M) was added to the catholyte solution to obtain a concentration of 0.1 M of D-glucose oxime (final volume of catholyte solution : 25 mL). The anolyte (25 mL) was a solution of 1 M perchloric acid in methanol. The reaction was conducted stirring at 25 °C, applying a constant potential of -3.5 V vs. the Ag pseudo-reference electrode. The solution was regularly sampled during the electrolysis for pH measurements (showing a constant pH of 6 maintained for all the electrolysis) and NMR analysis. Total charge was 9108 C, total electrolysis time was 15 h, and pH measured at the end of the electrolysis was 6. Current density slightly increased during the electrolysis from -0.0673 to -0.0793 A / cm2. After the electrolysis and concentration under reduced pressure at 25 °C, characterization by ESI-MS,XH and13C-NMR confirmed the presence of the product glucamine. Estimated yield with qNMR (using 4- hydroxy-trans-cinnamic acid as internal standard) was 54%.XH-NMR (400 MHz, D2O): 6 4.12 - 4.04 (m, 1H), 3.88 - 3.77 (m, 3H), 3.72 - 3.66 (m, 2H), 3.27 (dd, J = 13, 2.7 Hz, 1H), 3.13 (dd, J = 13, 9.6 Hz, 1H).13C NMR (101 MHz, D2O): 6 70.94, 70.75, 70.60, 68.96, 62.63, 41.66. ESI-MS [M+] : m / z calcd for [C6Hi6NO5]+182.0950, obsd 182.13.

[0102] Trial D

[0103] The same conditions as Example 2, Trial C were used. Total charge was 7305 C, total electrolysis time was 12.4 h, and pH measured at the end of the electrolysis was 6. Estimated yield with qNMR was 49%. This trial D confirms the reproducibility of the process of the invention.

[0104] Trial E

[0105] The same conditions as Example 2, Trial C were used. Total charge was 5753 C, total electrolysis time was 12.9 h, and pH measured at the end of the electrolysis was 6. Estimated yield with qNMR was about 50%. This trial E confirms the reproducibility of the process of the invention. Trial F

[0106] The same conditions as Example 2, Trial C were used. Total charge was 6140 C, total electrolysis time was 13.6 h, and pH measured at the end of the electrolysis was 6. Estimated yield with qNMR was 51%. This trial F confirms the reproducibility of the process of the invention.

[0107] Trial G

[0108] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M aqueous acetate buffer of pH 4 (20.45 mL). An aliquot (4.55 mL of oxime solution 0.55 M) of the solution obtained according to Example 1 was added to the catholyte solution to obtain a concentration of 0.1 M of D- glucose oxime (final volume of catholyte solution: 25 mL). The anolyte (25 mL) was an aqueous solution of 1 M perchloric acid. The reaction was conducted stirring at 25 °C, applying a constant potential of -2.5 V vs. the Ag pseudo-reference electrode. The solution was regularly sampled during the electrolysis for pH measurements and NMR analysis. Total charge was 6648 C, the total electrolysis time was of 6.9 hours, and the pH (maintained for the whole duration of the electrolysis) was 4. Current density was -0.0559 A / cm2. After electrolysis and concentration under reduced pressure at 25 °C, characterization byXH and13C-NMR confirmed the presence of the product glucamine. Estimated yield by qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 41%.XH-NMR (400 MHz, D2O): 6 3.90 - 3.76 (m, 4H), 3.67 (m, 2H), 2.91 (dd, J = 13.4, 3.4 Hz, 1H), 2.77 (dd, J = 13.4, 7.7 Hz, 1H).13C NMR (101 MHz, D2O): 6 73.48, 71.01, 70.99, 70.61, 62.85, 42.72. ESI-MS [M+] : m / z calcd for [CeHieNOs]* 182.0950, obsd 182.10.

[0109] Trial H

[0110] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M aqueous acetate buffer of pH 4. An aliquot of the solution obtained according to Example 1 was added to the catholyte solution to obtain a concentration of 0.2 M of D-glucose oxime (final volume of catholyte solution : 25 mL). The anolyte was an aqueous solution of 1 M perchloric acid. The reaction was conducted stirring at 25 °C, applying a constant potential of -3.5 V vs. the Ag pseudo-reference electrode. The solution was regularly sampled during the electrolysis for pH measurements and NMR analysis. The pH measured at the end of the electrolysis was 8, whereby the pH changed during the electrolysis from the pH of the buffer to 8. Estimated glucamine yield by qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 32%. This trial was repeated in galvanostatic conditions working at -0.37 A. This electric current was selected to have approximately the same current density than potentiostatic electrolysis. The trial using galvanostatic conditions afforded about the same yield as the one using potentiostatic conditions.

[0111] Trial I

[0112] The same conditions as Example 2, Trial H were used, but for the catholyte solution the present trial I used a 0.5 M acetate buffer (pH 6) in methanol. The anolyte was a solution of 1 M perchloric acid in methanol. The pH measured at the end of the electrolysis was 8. Estimated glucamine yield by qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 40%, in both potentiostatic and galvanostatic conditions.

[0113] Trial J

[0114] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using titanium as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Titanium was pretreated before the electrolysis with a 10% oxalic acid solution at 80 °C for 2 hours, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M aqueous acetate buffer of pH 4 (20.83 mL). An aliquot (4.17 mL of oxime solution 0.6 M) of the solution obtained according to Example 1 was added to the catholyte solution to obtain a concentration of 0.1 M of D-glucose oxime (final volume of catholyte solution : 25 mL). The anolyte (25 mL) was an aqueous solution of 1 M perchloric acid. The reaction was conducted stirring at 25 °C, applying a constant potential of -2.5 V vs. the Ag pseudoreference electrode. The solution was regularly sampled during the electrolysis for pH measurements (showing a constant pH of 4 maintained for all the electrolysis) and NMR analysis. Total charge was 8395 C and the total electrolysis time was of 11.8 hours. Current density was -0.0608 A / cm2. After electrolysis and concentration under reduced pressure at 25 °C, characterization byXH-NMR confirmed the presence of the product glucamine. Estimated yield by qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 39%.

[0115] Trial K

[0116] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using titanium as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Titanium was pretreated before the electrolysis with a 10% oxalic acid solution at 80 °C for 2 hours, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M acetate buffer in methanol of pH 6 (20.83 mL). An aliquot (4.17 mL of oxime solution 0.6 M) of the solution obtained according to Example 1 was added to the catholyte solution to obtain a concentration of 0.1 M of D-glucose oxime (final volume of catholyte solution : 25 mL). The anolyte (25 mL) was a solution of 1 M perchloric acid in methanol. The reaction was conducted stirring at 25 °C, applying a constant potential of -3 V vs the Ag pseudo- reference electrode. The solution was regularly sampled during the electrolysis for pH measurements and NMR analysis. Total charge was 8085 C, the total electrolysis time was of 19.9 hours, and the pH measured at the end of the electrolysis was 8. Current density was -0.0419 A / cm2. After electrolysis and concentration under reduced pressure at 25 °C, characterization byXH-NMR confirmed the presence of the product glucamine. Estimated yield by qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 23%.

[0117] Trial L (Comparative)

[0118] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was methanol with 0.1 M sodium perchlorate. An aliquot (4.55 mL of oxime solution 0.55 M) of the solution obtained according to Example 1 was added to the catholyte solution to obtain a concentration of 0.1 M of D-glucose oxime (final volume of catholyte solution : 25 mL). The anolyte (25 mL) was a solution of 0.1 M sodium perchlorate in methanol. The reaction was conducted stirring at 25 °C, applying a constant potential of -3.5 V vs the Ag pseudo-reference electrode. The solution was regularly sampled during the electrolysis for pH measurements (showing a pH increase from 8 to 11) and NMR analysis. Total charge was 1073 C, total electrolysis time was 5.1 h, and pH measured at the end of the electrolysis was 11. Current density was -0.0328 A / cm2. During the electrolysis, the formation of a white film was observed on the lead electrode surface. After the electrolysis, characterization byXH-NMR showed only the presence of the oxime, which was thus not able to undergo electroreduction.

[0119] Trial M (Comparative)

[0120] The same conditions as Example 2, Trial L (Comparative) were used, but for the anolyte solution the present Trial M used 0.17 M perchloric acid in methanol. Total charge was 2962 C, total electrolysis time was 8.9 h, and pH measured at the end of the electrolysis was 10. After the electrolysis, characterization byXH-NMR showed only the presence of D-glucose oxime, which was not able to undergo electroreduction.

[0121] Trial N (Comparative)

[0122] The same conditions as Example 2, Trial C were used, but the cathode was replaced with a graphite one and the electrolysis potential used was -2 V vs the Ag pseudo-reference electrode, as the previous one was not supported by graphite. pH measured at the end of the electrolysis was 6. Estimated yield of glucamine by qNMR was 2%, with a very high residual amount of D-glucose oxime.

[0123] Trial O (Comparative)

[0124] The electrolysis was conducted in a divided electrolytic cell using graphite as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo- reference electrode. The reaction mixture of the reaction step b) comprised 0.1 M D-glucose and hydroxylamine hydrochloride (1.5 eq), dissolved in the catholyte solution, i.e. 0.1 M acetate aqueous buffer of pH 4. The anolyte was a 0.1 M acetate aqueous buffer solution of pH 4.8. After stirring at room temperature, the solution above was subjected to electrolysis (step c)) at constant current (-0.2 A). Current density was -0.0595 A / cm2. pH measured after electrolysis was 9. NMR analysis after electrolysis did not show the presence of the product of interest, D-glucamine. This trial (comparative) is similar to the method disclosed in the prior art document Fedorohko, M. et al., Chem. Pap. 1994, 48, 274-277, but uses a graphite cathode instead of a mercury one and a different anolyte composition.

[0125] Example 3 - Electrosynthesis of the Ce-polyhydroxylamine D-glucamine via electrochemical reduction, starting from the Cs-polyhydroxylaldehyde D-glucose and ammonia or ions thereof

[0126] Trial A

[0127] The electrolysis was performed in an undivided electrolytic cell, using lead as working electrode (cathode), DSA® as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The solution of the reaction step b) comprised 0.06 M D-glucose (1 eq) and NH3 30% aq. (13 eq) dissolved in a saturated solution of NH4OAC in EtOH with the addition of 10% 0.1 M NaCICM aqueous solution (total solution volume 110 mL). The mixture was stirred for 4 hours to allow the formation of the imine. The mixture then was subjected to electrolysis in galvanostatic conditions at constant current (-0.2 A) for 3 hours, heating the solution at 60 °C. After 1 hour of electrolysis, 0.3 g of glucose were added. The registered potential during electrolysis was -3.5 V vs. the Ag pseudo-reference electrode. pH before and after the electrolysis was about 10. Estimated yield by qNMR (using 4-hydroxy-trans-cinnamic acid as internal standard) was 15%. The signals reported below are assigned to the glucamine product.XH NMR (400 MHz, D2O): 4.09 (m, 1H), 3.94 - 3.83 (m, 3H), 3.76 - 3.65 (m, 2H), 3.28 - 3.22 (m, 1H), 3.05 - 2.97 (m, 1H).13C NMR (101 MHz, D2O): 71.45, 71.27, 71.09, 62.96, 62.41, 37.72.

[0128] Trial B

[0129] The electrolysis was performed in an electrolytic cell divided by a porous septum, using lead as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. Both the catholyte solution (40 mL) and the anolyte solution (40mL) were a saturated solution of NH4OAC in EtOH with the addition of 10% 0.1 M NaCIO4 aqueous solution. To the catholyte solution, 0.05 M D-glucose and NH3 30% aq. (30 eq) were added for the reaction step b), whereby D-glucose imine was obtained. The reaction was stirred for 1 hour, and then the so- obtained solution was subjected to electrolysis (step c)) under constant potential of -3.5 V vs. the Ag pseudo-reference electrode, heating the solution from 25 °C to 60 °C for 18 hours. The solution was regularly sampled during electrolysis for NMR analysis. Total charge was 5169 C. pH maintained during electrolysis was 10. NMR analysis of the resulted crude products (brown oils), afforded after concentration under reduced pressure, showed the presence of the product glucamine, which was confirmed by the addition of a pure sample of commercial glucamine (peak matching). The estimated reaction yield was 17%. This Trial B allowed to obtain the desired product in a more easily reproducible way compared to Example 3, trial A, thanks to the use of a divided cell instead of an undivided one.

[0130] Trial C

[0131] The same conditions as in Example 3, Trial B were used, but for this trial the anolyte (40 mL) was a 1.7 M perchloric acid solution. Total charge was 9166 C. Current density slightly increased during the electrolysis from -0.1481 to -0.1538 A / cm2. pH measured at the end of the electrolysis was about 9. The estimated reaction yield was 15%.

[0132] Trial D (Comparative)

[0133] The electrolysis was performed working at constant current in a divided electrolytic cell (by porous septum or by Nation® 117 membrane), at 25 °C, with 0.1 M glucose and an excess of ammonia (5 eq) dissolved in the catholyte solution, i.e. a 0.1 M ammonium acetate aqueous solution, using a graphite cathode. The anolyte was 0.1 M potassium hydroxide aqueous solution. The applied current was -0.06 A (correspondent to a registered potential of -1.33 V vs. SCE). pH measured at the end of the electrolysis was 10. NMR analysis after electrochemical reduction did not show traces of the product of interest, D-glucamine.

[0134] Trial E (Comparative)

[0135] The electrolysis was performed using a reaction mixture of 0.05 M D-glucose and an excess of NH3 30% (30 equivalents), dissolved in the catholyte solution, i.e. a saturated solution of ammonium acetate in ethanol, which were subjected to electrolysis at 25 °C and at 60 °C, using a graphite cathode. The anolyte was 0.1 M potassium hydroxide aqueous solution. pH measured at the end of the electrolysis was 10. NMR analysis after electrochemical reduction did not show traces of the product of interest, D-glucamine.

[0136] Example 4 - Reaction of the C3-polyhydroxylketone dihydroxyacetone with hydroxylamine or ions thereof (step b))

[0137] Hydroxylamine hydrochloride (3.857 g, 0.0555 mol, 2.5 eq) was dissolved in dry MeOH (35 mL). Two drops of phenolphthalein (1% solution in EtOH) were added. A solution of sodium methoxide (3,059 g, 0.0566 mol, 2.55 eq) in dry MeOH (10 mL) was added slowly to the solution, upon which a white precipitate was formed. Addition of the base was halted when the mixture stayed pink for approximately one minute. The mixture was stirred for 40 minutes and filtered to remove salts. The filtrate was warmed to 70 °C, and 1,3- dihydroxypropanone (dihydroxyacetone) (2 g, 0.0222 mol, 1 eq) was added in small portions. The mixture was stirred at 70 °C for 2 h, then cooled to room temperature and stirred for 12 hours. An aliquot of the solution (3 mL) was concentrated to obtain a sample of the reaction product forXH and13C-NMR analyses, while the remaining part was used, without isolation, for the further electrolysis step. The NMR analysis showed a full conversion of dihydroxyacetone into the desired oxime.XH NMR (400 MHz, D2O): 6 4.37 (s, 2H), 4.18 (s, 2H).13C NMR (101 MHz, D2O): 5 160.41, 59.79, 55.43.

[0138] Example 5 - Electrosynthesis of the Cs-Ce-polyhydroxylamine serinol via electrolyzation of the solution of Example 4 (step c))

[0139] Trial A

[0140] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M acetate buffer in MeOH (20.54 mL) at pH 6. An aliquot (4.46 mL of oxime solution 0.56 M) of the solution obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime (final volume of catholyte solution : 25 mL). The anolyte (25 mL) was a solution of 0.6 M perchloric acid in methanol. The reaction was conducted stirring at 25 °C. A constant potential of -2.8 V vs. the Ag pseudo-reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total charge was 4491 C, total electrolysis time was 10.9, the pH at the end of the electrolysis was 6.5, and the current density was -0.0756 A / cm2. After concentration under reduced pressure at 25 °C, the reaction mixtures were characterized byXH and13C-NMR, showing, apart from some residual oxime, the desired product serinol, which was in approximately 1 : 1 ratio with the by-product 2-aminopropane. Estimated yield with qNMR was about 38%. The signals reported below are only the signals of the product serinol (the other signals of the by-products and starting reagent oxime are not reported).XH NMR (400 MHz, D2O): 6 3.85 (m, 2H), 3.75 (m, 2H), 3.43 (m 1H).13C NMR (101 MHz, D2O): 6 58.52, 53.94.

[0141] Trial B

[0142] The same conditions as per Example 5, trial A were used. For this trial B, the total charge was 3383 C, total electrolysis time was 12.2 h, the pH at the end of the electrolysis was 6.5, and the current density was -0.0272 A / cm2. Also for this trial, the desired product serinol, which was in approximately 1: 1 ratio with the by-product 2-aminopropane, was obtained with a yield of about 38%, demonstrating the reproducibility of the process.

[0143] Trial C

[0144] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using titanium as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Titanium was pretreated before the electrolysis with a 10% oxalic acid solution at 80 °C for 2 hours, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M acetate buffer in MeOH (20.54 mL) at pH 6. An aliquot (4.46 mL of oxime solution 0.56 M) of the solution obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime (final volume of catholyte solution: 25 mL). The anolyte (25 mL) was a solution of 0.6 M perchloric acid in methanol. The reaction was conducted stirring at 25 °C. A constant potential of -2.8 V vs. the Ag pseudo-reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total charge was 5582 C, total electrolysis time was 29 h, the pH at the end of the electrolysis was 8, and the current density was -0.028 A / cm2. After concentration under reduced pressure at 25 °C, the reaction mixture was characterized byXH-NMR showing, apart from some residual oxime, the desired product serinol, which was in approximately 1: 1 ratio with the by-product 2-aminopropane. Estimated yield with qNMR was about 20%. The signals reported below are only the signals of the product serinol (the other signals of the byproducts and starting reagent oxime are not reported).XH NMR (400 MHz, D2O): 6 3.79 - 3.73 (m, 2H), 3.65 (m, 2H), 3.34 - 3.29 (m, 1H).

[0145] Trial D

[0146] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using titanium as working electrode (cathode), platinum as counter electrode (anode) and a silver foil as pseudo-reference electrode. Titanium was pretreated before the electrolysis with a 10% oxalic acid solution at 80 °C for 2 hours, while silver foil was cleaned with SiC waterproof sanding paper P800. The catholyte solution was a 0.5 M aqueous acetate buffer (20.54 mL) of pH 4. An aliquot (4.46 mL of oxime solution 0.56 M) of the solution obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime (final volume of catholyte solution: 25 mL). The anolyte (25 mL) was an aqueous solution of 0.6 M perchloric acid. The reaction was conducted stirring at 25 °C. A constant potential of -2.5 V vs. the Ag pseudo-reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total charge was 9768 C, total electrolysis time was 13 h, the pH at the end of the electrolysis was 4, and the current density -0.1052 A / cm2. After concentration of an aliquot of the reaction mixture under reduced pressure at 25 °C, it was characterized byXH-NMR showing, apart from other by-products, the desired product serinol, which was in approximately 1 : 1 ratio with the by-product 2-aminopropane. Estimated yield with qNMR was about 33%. The signals reported below are only the signals of the product serinol (the other signals of the byproducts are not reported).XH NMR (400 MHz, D2O): 6 3.70 - 3.64 (m, 2H), 3.62 - 3.54 (m, 2H), 3.10 - 3.02 (m, 1H).13C NMR (101 MHz, D2O): 6 61.75, 53.29. ESI-MS [M+] : m / z calcd for [C3HIO02N]+92.07, obsd 92.0711. ESI-MS [M+] : m / z calcd for [C3HIOON]+76.08, obsd 76.0763.

[0147] Trial F

[0148] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using titanium as working electrode (cathode), platinum as counter electrode (anode) and Ag / AgCI (3 M KCI) as reference electrode. Titanium was pre- treated before the electrolysis with a 10% oxalic acid solution at 80 °C for 2 hours. The catholyte solution was a 0.5 M aqueous acetate buffer (20.76 mL) of pH 4. An aliquot (4.24 mL of oxime solution 0.59 M) of the solution obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime. The anolyte (25 mL) was an aqueous solution of 0.6 M perchloric acid. The reaction was conducted stirring at 25 °C. A constant potential of -2.4 V vs. the reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total charge was 8352 C, total electrolysis time was 8.3 h, the pH at the end of the electrolysis was 4, and the current density -0.083 A / cm2. After concentration of an aliquot of the reaction mixture under reduced pressure at 25 °C, it was characterized byXH-NMR showing, an estimated yield of about 23%.

[0149] Trial G

[0150] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and Ag / AgCI (3 M KCI) as reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis. The catholyte solution was a 0.5 M acetate buffer in MeOH (22.19 mL) at pH 6. An aliquot (2.81 mL of oxime solution 0.89 M) of the solution as obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime. The anolyte (25 mL) was a solution of 0.6 M perchloric acid in methanol. The reaction was conducted stirring at 25 °C. A constant potential of -2.8 V vs. the reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. This trial was interrupted before its completion; indeed, the total charge was 1137 C, and the total electrolysis time was 3.7 h. The pH at the end of the electrolysis was 6, and the current density was -0.028 A / cm2. After concentration under reduced pressure at 25 °C, the reaction mixtures were characterized byXH and13C-NMR, showing an estimated yield with qNMR of about 15%.

[0151] Trial H

[0152] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and Ag / AgCI (3 M KCI) as reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis. The catholyte solution was a 0.5 M aqueous acetate buffer (22.19 mL) at pH 6. An aliquot (2.81 mL of oxime solution 0.89 M) of the solution as obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime. The anolyte (25 mL) was an aqueous solution of 0.6 M perchloric acid. The reaction was conducted stirring at 25 °C. A constant potential of -2.5 V vs. the reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total charge was 10511 C, total electrolysis time was 12.5 h, the pH at the end of the electrolysis was 10, and the current density was -0.052 A / cm2. After concentration under reduced pressure at 25 °C, the reaction mixture was characterized byXH and13C-NMR, showing an estimated yield with qNMR of about 17%. Trial I

[0153] The same conditions as per Example 5, trial H were used, but with a lower total amount of charge, 6087 C. Qtotai / Qth = 6.31 instead of 10.89 (with Qtotai indicating the total amount of consumed charge = I*t; and Qth indicating the theoretical charge needed considering a 4- electron mechanism). For this trial I, total electrolysis time was 6.5 h, the pH at the end of the electrolysis was 10, and the current density was -0.041 A / cm2. The desired product serinol was obtained with a yield of about 24%.

[0154] Trial J

[0155] The same conditions as per Example 5, trial H were used, but using a different anolyte, that is 1 M HCIO4 aqueous solution (instead of 0.6 M). For this trial J, the total charge was 5054 C, total electrolysis time was 6.6 h, the current density was -0.040 A / cm2. The desired product serinol was obtained with a yield of about 17%.

[0156] Trial K (Comparative)

[0157] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and Ag / AgCI (3 M KCI) as reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis. The catholyte solution was 0.5 M acetate buffer in MeOH (22.19 mL) at pH 6. An aliquot (2.81 mL of oxime solution 0.89 M) of the solution as obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime. The anolyte (25 mL) was a solution of 0.6 M perchloric acid in MeOH. The reaction was conducted stirring at 25 °C. A constant potential of -1.5 V vs. the reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total charge was 1182 C, total electrolysis time was 15.5 h. The pH at the end of the electrolysis dropped to 3. The current density was -0.008 A / cm2. After concentration under reduced pressure at 25 °C, the reaction mixtures were characterized byXH and13C- NMR, showing that the desired product serinol was not obtained.

[0158] Trial L (Comparative)

[0159] The same conditions as per Example 5, trial K (Comparative) were used, but using a different anolyte, that is 0.1 M HCIO4 and 0.5 M NaCICk in MeOH (instead of 0.6 M HCIO4). For this trial L, the pH reached 9 after 724 C (Qtotai / Qth = 0.75), whereby small volumes of HCIO4 70% were added to lower the pH; pH at the end of the trial, after 1990 C, was 2. TheXH NMR analysis after concentration under reduced pressure at 25 °C showed that the desired product serinol was not obtained.

[0160] Trial M (Comparative)

[0161] The same conditions as per Example 5, trial L (Comparative) were used, but using a different anolyte, that is 0.5 M HCIO4 and 0.1 M NaCIO4 in MeOH (instead of 0.1 M HCIO4 and 0.5 M NaCIO4). For this trial M, the pH was maintained at 6, however theXH NMR analysis after concentration under reduced pressure at 25 °C showed that the desired product serinol was not obtained; this comparative trial shows that the concentration of protons within the anolyte can be important to allow the electroreduction of step c).

[0162] Trial N (Comparative)

[0163] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using lead as working electrode (cathode), platinum as counter electrode (anode) and Ag / AgCI (3 M KCI) as reference electrode. Lead was pre-treated with 0.1 M HCI solution before the electrolysis. The catholyte solution was an 0.5 M aqueous acetate buffer (22.19 mL) at pH 4. An aliquot (2.81 mL of oxime solution 0.89 M) of the solution as obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime. The anolyte (25 mL) was an aqueous solution of 0.6 M perchloric acid. The reaction was conducted stirring at 25 °C. A constant potential of -1.5 V vs. the reference electrode was applied and the solution was regularly sampled for pH measurements and NMR analysis. The total electrolysis time was 12.5 h, the pH at the end of the electrolysis was 3, and the current density was -0.008 A / cm2. After the electrolysis (2140 C, Qtotai / Qth = 2.22) and concentration under reduced pressure at 25 °C,XH NMR analysis showed that the desired product serinol was not obtained.

[0164] Trial O (Comparative)

[0165] The same conditions as per Example 5, trial P (Comparative) were used, but with a 1 M HCIO4 solution as anolyte (instead 0.6 M). The pH at the end of electrolysis (8604 C, Qtotai / Qth = 8.92) dropped from 6 to 2. No observation of the desired product serinol was observed afterXH NMR analysis.

[0166] Trial P

[0167] The electrolysis was performed in an electrolytic cell divided by a cation exchange membrane (Nation® 117), using zinc as working electrode (cathode), platinum as counter electrode (anode) and Ag / AgCI (3 M KCI) as reference electrode. Zinc was pre-treated with 0.1 M HCI solution before the electrolysis. The catholyte solution was an 0.5 M aqueous acetate buffer (21.06 mL) at pH 6. An aliquot (3.94 mL of oxime solution 0.63 M) of the solution as obtained according to Example 4 was added to the catholyte solution to obtain a concentration of 0.1 M of oxime. The anolyte (25 mL) was an aqueous solution of 0.6 M perchloric acid. The reaction was conducted stirring at 25 °C and in galvanostatic conditions at -0.038 A cm'2. The total electrolysis time was 11.7 h, and the pH at the end of the electrolysis was 5.XH NMR analysis showed that the desired product serinol was obtained with a yield of about 6%, demonstrating that the product is obtainable also using a zinc-based cathode.

[0168] Trial Q

[0169] First, 2-phenyl-l,3-dioxan-5-one was reacted with hydroxylamine hydrochloride following the same procedure used in Example 4. The reaction mixture was then analysed byXH NMR,13C NMR and IR, confirming the complete conversion from ketone to oxime. Then, the same conditions as per Example 5, trial I were used, but with an acetate buffer in EhO / MeOH (1: 1) at pH 6 as catholyte. The electrolysis was conducted in galvanostatic condition with a current density of -0.032 A cm-2and a total charge of 1713 C (Qtotai / Qth = 4.44). The total electrolysis time was 6 h and the pH at the end of the electrolysis was 5. Upon deprotection via acidification of the sample with 0.5 M HCI, reaching a final pH of 2,XH NMR showed the desired product serinol with a yield of about 11%, demonstrating that it is possible to obtain the desired product also with Cs-Ce-polyhydroxyl-aldehydes or - ketones that have one or more hydroxyl groups thereof linked to one or more protecting groups, such as alkyl groups. Summary of Examples

[0170] Table 1 summarizes the main conditions, parameters, and products obtained for each Trial above. In Table 1, DHA stands for dihydroxyacetone (a Cs-polyhydroxylketone), pHsis the starting pH (that is, the pH before the electroreduction of step c)), pHf is the final pH (that is, the pH upon interruption of the electrolysis), and Comp, indicates a comparative trial.

[0171]

[0172] Table 1

[0173] Table 1 highlights that carrying out step c) while maintaining the pH within the ranges provided according to the process of the invention, as well as by using cathodes and the starting reagent to be reacted in step b) according to the process of the invention, allows to manufacture effectively the desired polyhydroxylamine in a reproducible way without employing harsh reducing reagents or conditions (such as hydrogen gas under high pressure and temperature), or toxic cathodes (such as mercury-based cathodes), and obtaining yields possibly even higher than 50%.

Claims

CLAIMS1. A process for manufacturing a Cs-Ce-polyhydroxylamine comprising the following steps: a) providing an electrolyte solution comprising: i. a Cs-Ce-polyhydroxylaldehyde or a Cs-Ce-polyhydroxylketone; and ii. hydroxylamine or ions thereof, or ammonia or ions thereof; b) reacting the Cs-Ce-polyhydroxylaldehyde or a Cs-Ce-polyhydroxylketone with hydroxylamine or ions thereof, or with ammonia or ions thereof; c) electrolyzing the electrolyte solution obtained in step b) to obtain the C3- Ce-polyhydroxylamine; wherein, the cathode is based on a material that has an exchange current density (jo / A cm'2) lower than IO-7, provided that the cathode is not mercury-based; and wherein the pH during step c) is maintained: at 10 or lower, when the electrolyte solution of step a) comprises hydroxylamine or ions thereof; or at 11 or lower, when the electrolyte solution of step a) comprises ammonia or ions thereof.

2. The process according to claim 1, wherein the pH is maintained:- when the electrolyte solution of step a) comprises hydroxylamine or ions thereof, at 9 or lower; preferably at 1 to 9; more preferably at 4 to 9; even more preferably 4 to 8, and most preferably at 4 to 7; or- when the electrolyte solution of step a) comprises ammonia or ions thereof, at 10 or lower; preferably at 1 to 10; more preferably at 4 to 10; even more preferably at 6 to 10; and most preferably at 7 to 10.

3. The process according to claim 1 or 2, wherein the electrolyte solution is selected from the group consisting of aqueous solution, methanol, ethanol, n- propyl alcohol, / -propyl alcohol, n- butyl alcohol, / - butyl alcohol, sec- butyl alcohol, t-butyl alcohol, and mixtures thereof.

4. The process according to claim 3, wherein the electrolyte solution is selected from the group consisting of aqueous solution, methanol, ethanol, and mixtures thereof.

5. The process according to any one of claims 1 to 4, wherein cathode is based on an element selected from the group consisting of zinc, silver, tantalum, tungsten, molybdenum, tin, lead, titanium, and mixtures thereof.

6. The process according to claim 5, wherein the cathode is based on an element selected from the group consisting of lead, titanium, zinc, and mixtures thereof.

7. The process according to any one of claims 1 to 6, wherein the C3-C6- polyhydroxylamine has the following formula (I):Formula (I) wherein : n is an integer number from 0 to 3, andR1, R2, R3, and R are independently selected from the group consisting of hydrogen, hydroxyl group (-OH), and primary amine group (-NH2), provided that at least two among R1, R2, R3, and R are hydroxyl groups (-OH), and only one among R1, R2, R3, and R is a primary amine group (-NH2).

8. The process according to claim 7, wherein : the Cs-Ce-polyhydroxylamine is selected from the group consisting of serinol, isoserinol, glucamine, 1-amino-l-deoxy-arabinitol, 1-amino-l-deoxy-xylitol, 1- amino-l-deoxy-ribitol, 1-amino-l-deoxy-galactitol, and 1-amino-l-deoxy- mannitol; and the Cs-Ce-polyhydroxylcarbonyl is selected from the group consisting of glyceraldehyde, erythrose, threose, ribose, arabinose, xylose, lyxose, glucose, mannose, galactose, dihydroxyacetone, erythrulose, ribulose, xylulose, fructose, psicose, sorbose, and tagatose.

9. The process according to claim 8, wherein the Cs-Ce-polyhydroxylamine is serinol, isoserinol, or glucamine; and the Cs-Ce-polyhydroxylcarbonyl is dihydroxyacetone, glyceraldehyde, or glucose.

10. The process according to any one of claims 1 to 9, wherein at least step c) is carried out within an electrolytic cell formed by two-compartments divided by a permeable separator (divided electrolytic cell), and wherein the pH is maintained in the ranges as defined in any one of claims 1 to 9 at the catholyte.

11. The process according to claim 10 wherein, when the electrolyte solution of step a) comprises hydroxylamine or ions thereof, the concentration of protons (H+) within the anolyte is equal or higher compared to the concentration of protons within the catholyte.

12. The process according to claim 10 or 11, wherein the concentration of protons (H+) within the anolyte is higher than 0.5 M; preferably, the concentration of protons (H+) within the anolyte is 0.6 M or higher.

13. The process according to any one of claims 1 to 12, wherein step b) is carried out by reacting Cs-Ce-polyhydroxylcarbonyl with hydroxylamine or ions thereof in a molar ratio of 5: 1 to 1: 10, preferably of 3: 1 to 1:5, more preferably of 3: 1 to 1 :3, and even more preferably of 1 : 1 to 1:

3.

14. The process according to any one of claims 1 to 12, wherein step b) is carried out by reacting Cs-Ce-polyhydroxylcarbonyl with ammonia or ions thereof in a molar ratio of 3: 1 to 1:30, preferably of 2: 1 to 1 :20, more preferably of 1: 1 to 1:20, even more preferably of 1:5 to 1: 15, and most preferably of 1 : 10 to 1: 15.

15. The process according to any one of claims 1 to 14, wherein the electrolyte solution, preferably the catholyte solution and / or the anolyte solution (when a divided electrolytic cell is used), at least during step c), comprises an acid, an acid salt, and / or a buffer.

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