BE529266A - - Google Patents

Description

       

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   Chloramphenicol is known to be D-threo-1-p.nitrophenyl-2-dichloroacetamino-3,3-propandyol. Synthetic methods always result in racemic compounds; it is therefore necessary, at a certain stage in the synthesis of chloramphenicol, to separate the optical antipodes, so as to obtain the derivative of the D-threo series. By splitting the optical antipodes on the threo-phenylaminodiols, the antipode L has remained unused until now; on the other hand, by operating on erythro-phenylaminodiols, the antipode L- is used, and the D- is left aside. It is obvious that, from a chemical point of view, the forms thus abandoned can only be used on condition of returning to the racemic compound.



   Any attempt to racemize them, however, was in vain; with thermal methods, the substance decomposes, before reaching the temperature required for racemization; and the latter is not produced by other less energetic means.



   The present invention starts from the following considerations, the phenylaminopropanediols, corresponding to the general formula:
 EMI1.1
 contain the two asymmetric carbon atoms 1 and 2, and it is also to this fact that their resistance to direct racemization is due. But if we eliminate a center of asymmetry, or both, by introducing for example double bonds, we can arrive at a substance free of asymmetric carbon atoms, on which we can reconstruct the amino diol chain; or else we arrive at a compound with a single center of asymmetry, so as to facilitate its transformation into a racemic compound.



   For example, if one transforms the secondary alcoholic group of phenylaminodiols into a ketone group, one eliminates the asymmetry of the carbon atom in position 1 and one obtains a compound which, having a single asymmetric carbon atom, is obtained. in position 0 (with respect to a ketonic group, lets hope for a greater ease of racemization. It is known, in fact, that the substances having a center of asymmetry adjacent to a group which mobilizes a hydrogen atom of the carbon asymmetric, for example Ó -amino acids) are almost always convertible into racemic substances.



   In the case which interests us, it was observed experimentally that the ketones, obtained by oxidation of [alpha] -acylamino-ss-acyloxy-derivatives of phenylaminopropandiols, give rise to the disappearance of the optical rotation, but that this disappearance of the optical rotation is in fact mainly due to the formation of a new compound, from which the centers of asymmetry are eliminated due to the elimination of the acyloxy group in / 3 -, due to the union with the hydrogen atom in Ó -, with formation of an unsaturated compound, having a double bond between the carbon atoms 0 (and mpos
This transformation has been verified, even recently, by operating on racemic derivatives (C.F. HUEBNER et al., J.Org.Chem. 18, 21 (1953);

   KUNIZO OSUGI, Chem.Ab. 47, 2749 (1953), and it is used by the present invention to obtain the starting material, on which the amino diole chain is reconstructed. In addition, the mechanism of the reaction has formed the subject of an in-depth study, by which the inventors have succeeded in demonstrating, by means of quantitive measures of the reaction rate, that this is influenced by several factors;

   particularly by the presence of the nitro group in position.para-, by the acylamino group in Ó and by the acyloxy group in ss

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The following table gives the rate constants of the reactions carried out in pyridine, at room temperature, with different Ó-acylamino- ss -acyloxy-propiophenones, substituted in various ways in their nucleus.



   The reaction rates, measured on the basis of the decrease in optical rotation, all follow, with a good approximation, a first order mechanism:
 EMI2.1
 Compound K 1st order in minutes.



  Dp.nitro- 0 (-dichloroacetamino- / 3 -benzoxy-propiophenone 34.5.1C3 Dp.nitro- -benzamino- /; -benzoxy-propiophenone 10.8. Z D "'p .ni tro- 0 (-acetamino- / 4 -benzoxy-propiophenone z. 10-3 Dp.nitro- -acetamino -acetoxy-propiophenone 3.91. 10 * 3 Lm, nitro- / 4fi -acetamino- if -acetoxy-propiophenone 2.31. 3.0-3 D- 0 (-acetamino -./3 -acetoxy-propiophenone 0.27.

   10-3 Dp.acétami.no- a -acetamino- -acetoxy-propiophenone 0 It can easily be seen that the elimination reaction is favorable precisely by the substituted groups, the theory of which predicts the favorable action, i.e. say, having electromic affinity (2nd class substituents), in the para position more than in the meta position, and by the acyl radicals of the strongest acids, either Ó or '3 with respect to the keto group.



   The reaction even takes place spontaneously at room temperature, but very slowly; by raising the temperature, the reaction accelerates, but the acrylophenone thus obtained is made impure by products due to the successive condensation of acrylophenones, probably dimers having the formula:
 EMI2.2
   There are, however, substances which greatly accelerate the rate of said elimination reaction, so as to initiate it within a few hours at room temperature.

   It is a property of all compounds with a basic function, whether they are inorganic such as sodium hydroxide, potash, etc., or else organic such as primary, secondary or tertiary, cyclic, heterocyclic or aliphatic amines (pyridine, di- thylamine, etc.), alkali alcoholates or enolates, alkali salts of organic acids, organometallic derivatives of alkali metals, and so many other basic agents, even if they are not explicitly indicated here.



    By employing caustic alkalis in stoichiometric amounts with respect to Ó-acylamino-ss -acyloxy-p; ropiophenones, possibly phenyl-substituted, for example p.nitro, the elimination reaction is almost instantaneous, so that the compounds (I) behave like weak acids; but it is preferable to operate with less energetic catalysts, such as organic bases, or traces of alkaline alcoholates; it is also preferable to work in an anhydrous environment.

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   Examination of the reaction rates determined by the application and the study of the influence of the β group have thus led to the supposition that, by reducing the electronic affinity of said group, the rate of the reaction d The elimination would have been reduced, but not to a sufficient extent to give rise to hope that the racemization reaction would have taken precedence over the elimination reaction.

   The Applicant then observed, with surprise, that by operating on Ó -acylamino-ss-hydroxy-propiophenones (including those which are substituted in the nucleus, that is to say p.nitropropiophenones), under the same conditions as those mentioned above, the racemization reaction greatly predominates, thus proving that the speed of the elimination reaction has slowed so low, that it allows the process of racemization.



   On the basis of these data, according to the present invention, two routes are opened to obtain the transformation of aminodiols into their corresponding racemic compounds: 1) racemization of Ó-acylamino-ss -hydroxy-propiophenones, substituted or not,
2) formation of the aminodiolic chain again on the Ó-acyl-amino-acrylophenones, substituted or not.



    If one follows the first route (route 1) it is essential to obtain, as starting material, the Ó-acylamino-ss -hydroxypropiophenones, the process of which is known for obtaining by N-acylation of the Ó-amino salts. ss -hydroxy-propiophenones.



   The Applicant has studied, on the contrary, a faster method for arriving at said D- and L- Ó -acylamino-ss -hydroxy-propiophenones; and this precisely by oxidizing directly and selectively the D- and L-threo and the erythro-N-acylamino-derivatives of phenyl-aminopropanediols, optionally phenyl-substituted.



   This process can be carried out by treating the N-acrylaminodiols with halogens in aqueous solution, at a temperature between 0 and 50 ° C., preferably in the presence of actinic light.



   Instead of halogen, a compound which liberates halogen, in particular an alkali bromate, can advantageously be employed for this reaction. Thus, it is possible to operate with advantage with sodium bromate in the presence of hydrobromic acid.



   Racemization of the D- and L- Ó-acylamino-ss-hydroxy-propiophenes thus produced takes place by operating under the same conditions and with the same catalysts as those indicated for the elimination reaction.



   For this racemization, however, it has been found that, as substances of a basic nature, alkali metal bicarbonates in aqueous solution, in particular sodium bicarbonate, are very suitable for achieving the intended aim.



   The racemic O (-acylamino- ss -hydroxy-propiophenones are thus obtained, which can be converted into the corresponding aminodiols by methods known by other patented methods for the benefit of the same applicant.



   If the second route is chosen (route 2), the compounds resulting from the elimination reaction, represented by formula (V) of the scheme given below, and which can be obtained by oxidizing, are used, by known methods (see CG Alberti and others, La Chimica and Industria,

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 EMI4.1
 , 5 (1951) and azz.Gh3.ra.It. 82, 53 (1952), D- and L-threo- and erythrol-pbenyl-2-aeylaiBino-3-acyloxy-propan-1-ols (possibly phenyl-aubst3.tués) (see patent application in Italy) not. 6530/51 verb. l4ilano 6062/51 cl. and C.G..berti and others, Gazz.Ghim..It 82, 63 (1952).



  The products of the elimitation reaction can react, either cour me 0 (-acylimino-propiophenones:
 EMI4.2
 or as Ó -acylamino-acrylophenones:
 EMI4.3
 
With an aqueous hydrohalic acid, they react according to the first form, giving, by reaction of hydrolysis, phenyl-methyl glyoxals:

   
 EMI4.4
 
On the contrary, with an anhydrous hydrohalic acid (HCl, HBr, HJ) dissolved in an ether (such as ethyl or proyl ether, tetrahydrofuran, dioxane, etc.) at temperatures varying between
 EMI4.5
 0 and 100 C, the compounds (V) react in the form of acrylQù @ 9s (Vu), and there is an addition reaction of the elements of hydrohalic acid to the double bond, so as to form c> (-acrylamino -bp- logeno-propiophenones.



   The latter can be reduced with a boron and sodium or boron and potassium hydride, in an alcoholic or aqueous or even aqueoalcoholic solution, so as to transform the keto group into an alcoholic group.



  This reduction can also be carried out with an aluminum alcoholate, in the presence of excess alcohol; for example aluminum isopropylate and isopropyl alcohol; or even with another selective reducing agent, which does not alter the nitro- group, such as boron and lithium hydride, or lithium and aluminum hydride, in ethyl ether or tetrahydrofuran solution.



   By reducing the ketone group, we introduce, next to
 EMI4.6
 the asymmetric carbon atom of the c ('- halogérlo-propiophenones. a second center of asymmetry, so that the D, h-1-phenyl-2-acylau.no-3-halogenopropan-1-ols optionally phenylsubstituted by p-nitro example) obtained are a mixture of the threo- and erythro forms.



  Both components of the nélesge can be repaired by fractional crystallization in an appropriate solvent: eg methanol, ethanol, chloroform, benzol. Or the mixture can be used as it is for the subsequent conversion, by reacting the halo-derivative into a solution.
 EMI4.7
 alcoholic or aqueous or aqueo-alcoholic tion, with an alkaline hydrate (mach, KOH, etc.) cold, for 10 to 15 hours, or even at boiling

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 for 5 to 30 minutes, to replace the halogen with the oxhydril.



   One thus obtains D, L-threo- or D, L-erythre-1-phenyl-2-acylamino-1,3-propandiol (optionally phenylsubstituted) (VIII), depending on whether one started from halo - corresponding derivative, threo-or erythro. If the mixture of halo-derivatives is used, the threo- and erythro- derivatives must then be separated by fractional crystallization from methanol, ethanol, or even water, from the resulting acyl-aminodiols.



   To obtain the corresponding aminodiols, one proceeds finally by the known methods (LMLong and HDTrautman, J.Am.Chem.Soc, 71, 2473 (1949); CGAlberti and others, Chimica and Industria. 33 , 5 (1951); J. Controulis et al., J. Am. Chem. Soc. 71, 2463 (1949).



   Since the substances considered in this specification contain one or two asymmetric carbon atoms, they can exist in the dextrorotatory, levorotatory, or racemic form, and, for each of them, in the erythro- (reg. Or ci) form and threo (or trans). It is therefore understood that, in the present description and in the appended claims, reference is made to any one of these forms, unless otherwise indicated.

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 EMI6.1
 



  Route> axa Route 1 1- <> - CH - CH - CHH Volg D- or CH - CH - OH20H threo or (I) erythro OH NH2 D- or L- CH - CH - CH200CR '(II) or erythro OH IH e C OR or erythro OCCR Nli2-HCl (X) DF or L- -CH - CH - CH2.OCOR. ' (III) threo erythro NHCCR -E- or erythro OH NHC #.



  D- or 00 CH - CH2011 D- or L- 00 - CH - CH2011 D- or L- -CO - CH - CH20COR '(IV) IV, GI e C vit NH.CCR lYAz o HC, .1, y 1 NH.COR (XI) NH, 2.HCl NH.OOR (XII) (xi) (XII) (XI)> - o - C ::: CH2 (V) i'f.C1 e C 0R D, L- -CH - CH - OH20H DL- - CO - CH - CH2X (VI) -threo and erytbro y OH NII.CCR (VI y NHeC011 D, - CO - CH - CH20H tb: <-CE - CH - CH20H tbr 5- CH - CH - CH2X (VII) NH.COR (XIII) throo y OH NH2 (IX) et-ythro OH lüHpCOR X = Cl, Br, J; Y = N0 or H; R 0 f- B. ':: alkyl , halo-alkyl, aryl, aralkyl, H.

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   By way of non-limiting demonstration, some examples of execution of the invention will be described below.



   EXAMPLE 1.



   28.2 g of L-threo are boiled under reflux for 1.5 hours.
 EMI7.1
 1-phenyl-2-amino-1,3-prophnediol (I) with 25 cm3 of methanol and 26 cm3 of methyloic dichloroacetate to obtain L-threo-1-phenyl-2-dichloroacetamino-1,3-propanediol ( X), mp 92-93 (in benzene); (Ó Ó) D = +2.5 + 2 (c = 4, methanol). 10.0 g of L-threo-1-phenyl-2-dichloroacetamino-1,3-propanediol (X) are dissolved in 10 cm3 of dioxane and
 EMI7.2
 3.1 cm3 of acetic anhydride at 000 are added thereto. After one night, the mixture is poured into concentrated HCl added with ice and the mixture is extracted with ethyl acetate.

   The crude residue in the oily state, consisting of L-threo-1-phé
 EMI7.3
 nyl-2-dichloaBacetamlno-3-acetoxy-propan-1-ol (III) is oxidized with sodium dichromate and sulfuric acid to obtain D- o (-dichloroacetamino-3 -acetoxy-propiophenone (IV). This is dissolved, without purifying it, in pyridine and left overnight at room temperature. By pouring into ice and concentrated hydrochloric acid, a precipitate is obtained. Crystalline media, of which, by extraction with ethyl acetate and crystallization from ethyl acetate-petroleum ether, we
 EMI7.4
 obtains -dichloroacetamino-acrylophenone (V), mp; 118-120. 25.0 g of OC-dichloroacetaino-aerylophenone (V) are dissolved in 100 µm3 of anhydrous dioxane containing 28 g of gaseous HCl.

   After one night, poured into ice and filtered the product which crystallizes and which consists of D, L-
 EMI7.5
 -dichloroacetamino -chloropropiophenone (VI), m.p. 129 1 0 C (in methanol). 20.0 g of D, L- 0 (-dichloroacetamlno - /. :: J -chloropropiophenone (VI) are dissolved in 80 cm3 of methanol and reduced with 1.3 g of boron sodium hydride at 20-25 Ce Diluted with water and extracted with ethyl acetate to obtain an oily residue consisting of the mixture of D, L-
 EMI7.6
 erythro and threo-1-phenyl-2-dichZoroacetamino-3-chlorapropar-1-o1 (VII) which is not purified, but which is dissolved in 60 cm3 of methanol and which is treated, dropwise drop, with 18 cm of NaOH at 20; 6 at boiling point: 1 in.

   The crystallized sodium chloride is filtered off and the methanol is evaporated off. The residue is dissolved in 10% HCl and heated at 60-70 for 5 minutes.



  After cooling, the mixture is basified to m.H = 7.5 and extracted with ethyl acetate. The residue of evaporation is crystallized from water to obtain
 EMI7.7
 hold the D, L-threo-1-phenyl-2-dichloro-acetamino-1,3-propaaédiol (VIII), m.p.



  95-97.



    EXAMPLE 2.



   20.0 g of L-threo-1-phenyl-2-amino-1,3-propanediol (I) are dissolved in 30 cm3 of glacial acetic acid; add 100 cm3 of saturated hydrochloric acid solution in glacial acetic acid and then 100 cm3 of acethyl chloride and the mixture is left to stand overnight. Then diluted with 500 cm3 of ether to crystallize L-threo-1-phenyl-1,3diacetoxy-2-amino-propane hydrochloride (II) which is then filtered, m.p. 153.5-
 EMI7.8
 154.5; (o () D = -13.8 J: 3 (c = 4; nethanol). 10.5 g of L-threo-1-phenyl-l, 3-diacetoxy-2-aminopropane hydrochloride (II) are dissolved in 21 cm3 of water and 3.6 g of NaHCO3 dissolved in 300 cm3 of water at temperature
 EMI7.9
 ambient.

   L-tbreo-1-phenyl-2-acetamino-3-acetoxy-propan-1-ol (III) which crystallizes, m.p. 121-122 C (in water); (O () D = + 6.7 t 1 (c = 4; methanol). 11.0 g of L-threo-1-phenyl-2-acetamino-3acetoxypropan-1-ol (III) are dissolved in 69 cm3 of chloroform and oxidation thereof is carried out with sodium bicromite and sulfuric acid in aqueous solution to give D- 0 (-acetamino- -acetoxypropiophenone (IV), mp 106-108 C (in ethanol); (0 () D = - 36.5 (c = 4; methanol). 25.5 g of D- 0 (-acetamino- B-acetoxypropiophenone (IV) are heated with 40 em3 of concentrated HCl, diluted with 32 cm3 of water, in a water bath, until complete dissolution.



  It is distilled off under vacuum and the residue is taken up in methanol, so as to

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 EMI8.1
 crystallize the hydrochloride of DD (-amino-J9 -hydroxypropiopbenone (si), mp 179-18000; 0 () D = -42.5 ¯ + 0.5 (c = 2; methanol). 8 g of said hydrochloride are dissolved in 70 g of a mixture of water and crushed ice and 6.5 cm3 of benzoyl chloride are added, at a temperature between
 EMI8.2
 At 0 and 50C, 10.5 g of sodium acetate dissolved in 15 cm3 of water are added and the mixture is stirred for 3 hours, after which the D- -benzoylamino -, / 3 -hydroxyprop-lophenone (XII) is filtered. which crystallizes; m.p. 138-140 G (in ethanol); (oG) D = + 2.5 + .r5 (c = 2; methanol}. 10 g of D- O (-benzoylmnino-j3 -hydroxypropiophenone) are dissolved in a mixture of pyridine and triethylamine.

   After 3 hours, the mixture is poured into ice and into concentrated hydrochloric acid and the D, L- 'Y-benzoyl-amino-VI -hydroxypropiophenone (XIII), p,' is filtered. 141-142 C (ethanol). To 10 g of D, L- '-benzoylaminoss -hydroxypropiophenone (XIII) is added a small amount of Raney nickel in 100 cm3 of methanol and the hydrogenation is carried out at 10 atm. until complete absorption of hydrogen.

   After filtration of the catalyst, the ethanolic solution is concentrated in order to crystallize the resulting residue.
 EMI8.3
 titué by a mixture of D, L-threo and erythro-1-phenyl-2-benzoylamino-1,> propandiol (VIII), from where, by crystallization in ethanol-water, the D, L- threo-1-phenyl-Z -ber.2aylamino-1,3-propanedial, mp; 165 -167 G, which, saponified by boiling with 20% HCl gives D, L-threo-1-phenyl-2-amino-1,3-propanediol (IX), m.p. 82 -84 C.



    EXAMPLE 3.
 EMI8.4
 



  10 g of L - (+) - 1-p, nitrophenyl-2-awino-1,3-propanediol (CI) are suspended in 24 uspension saturated solution of hydrochloric acid in acetic acid (approximately 11%), and 16 cm3 of acetyl chloride are added thereto.
 EMI8.5
 the. After one night, the L - (+) - 1-p.nitrophenyl-1,3-diacetoxy-2-aminopropano-hydrochloride (II) is filtered off which, once purified in methanol and ether, has a m.p. of 170-172C, and (0 <) D = +6 5 (c = 4.18: methanol).



    13 g of L-threo-l-p.nitrophenyl-l, 3-diacetoxy-2-amino-propane hydrochloride (II) are dissolved in 100 cm3 of water; 120 cm3 of ac-
 EMI8.6
 tone, then 25 cc of Naos N / 2 at 0 C. After 2 hours at 0 C, neutralized with HCl N / 1 and the acetone distilled off in vacuo.



   Then extracted with ethyl acetate and, by evaporation
 EMI8.7
 Subsequently, L-threo-p.nitrophenyl-2-acetamino-1,3-propanediol (X) is obtained at m.p. 134-136 C and (pC) D = -765 (c = 5.22; ethanol).



  We dissolve in 200 in? of water, 25.0.5 h - threo-1-p.nitro-phenyl-2-acetamino-1,3-propanediol (X); 5 cm3 of bromine are added to it, while stirring, in sunlight and at a temperature of 30 C. Extraction is carried out with ethyl acetate and, from the solution in ethyl acetate, one obtains , by evapo-
 EMI8.8
 ration, Dp, nitro- -acetami.; o-hydroxy propiophenone (XII), with melting point 142-144 C eu (o () D = +32 (c = 13; pyridine), or else (e) D = +22 (C = 2.0: ethanol).



   This ketone alcohol is also obtained by heating in a water bath
 EMI8.9
 a mixture of 30 g of D-p.nitra- -acetamino-fi -acetoxy-propiophenone (IV) and 40 cm3 of concentrated HCl, diluted with 32 cm3 of water. Immediately after dissolution, the mixture is cooled so as to crystallize the hydrochloride of D-p. or-
 EMI8.10
 tro- el -amino - / "1-hydroxypropiophenone (XI) s p, f, 192C and (o () D = -55 (c = 4.9 H2O).



  17 g of this alfec 50 d5 - au hydrochloride, 100 g of ice and 8 cm? acetic anhydride, then added to the solution 22: μ of sodium acetate. as crystals in 30 cm3 of water. D-p-nitro- -acetamino-9 -hydroxy-propiophenone (XII) crystallizes: m.p. 142-1440C.

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  EXAMPLE 4.



  The operation is carried out in the same way as in Example 3; but we start from
 EMI9.1
 D-threo-1-p.nitrophenyl-2-acetamino-1,3-po3lreacl.iol: ï t, el obtains L-panitrophenyl- 0 (-acétamino- / d -hydroxy-propiophenone (XII), at mp 142-144C and () D = -32 (c = 13; pyridine) or else - 22.5 (c = 2; ethanol).



   EXAMPLE 5.
 EMI9.2
 5 g of D-.acétaiBino -, / 7 -hydroxy-p.nitro-propiophenone (XII) are dissolved at m.p. 142-144 C; (Ó) D = +32 (c = 13; pyridine), in 40 cm3 of anhydrous pyridine; left at room temperature (about 20) for 140 hours. We observe from the start, by controlling samples, that the optical rotation decreases according to a logarithmic function. When
 EMI9.3
 as racemization is advanced, Dol- 0 (-acetamino-hydroxy-p.nitropropiephenone (XIII) begins to separate in the form of small yellowish crystals, which are collected at the end of the operation, to wash them with a little ether and air dry them.

   
 EMI9.4
 25.2 of D, Lp.nitro- 0 (-acetamino- ss -hydroxy-propiophenone (XIII) are then suspended in 80 cm3 of deacidified methanol, and added, with stirring, 2 g of boron- 91% potassium hydride, dissolved in 10 cm3 of boiled water, maintaining the temperature between 25 and 30 C
After 20 minutes, a further 4 cm3 of concentrated HCl is added, and
 EMI9.5
 leerythro-1-p.nitrophenyl-2-acetamino-1,3-Propandiol (VIII) is allowed to crystallize at m.p. 184-185 C. which rises to 195 C. after purification.



   The mother liquors from crystallization are evaporated to dryness, and the residue is extracted with ethyl acetate. By concentrating the solution in ethyl acetate, threo-1-p.nitrophenyl-2-acetamino-
 EMI9.6
 1,3-propandiol (VIII), at m.p. 157-1620C, which rises to 166% after further crystallization.,
EXAMPLE 6.



     We operate in the same way as in example 5, but we start
 EMI9.7
 Lp.nitrophenyl-2-acetamincrl, 3-prpanediol (X), (0 () D = 2 (c = 13, pyridine), mp 142-144 C; and we still obtain the D, L- 0 < -acetamino- jj -hydraxy p.itro-propicphenene (XIII) at mp 162-1040.



  EXAMPLE 7.



  In a flask, 10 g of L-threo-1-p.nitrophenyl-2acetamino-1,3-propanediol (X) and 2.2 g of sodium bromate are dissolved in 120 em3 of water and 0.6 g of water are added. 48% hydrobromic acid. It is left to stand in sunlight for a day, then the D-p.nitro-
 EMI9.8
 01 -acetamino- -hydrxy-prpiphenone (XII) crystallized, m.p. 140-142 C. 10 g of D-p.nitre- O / -acetamino- / 3 -hydroxyprepiephenone (XII) are suspended in 150 cc of 5% sodium bicarbonate solution and stirred from time to time. After one night, the D, L-p.nitrophenyl-O (-acetamino- -hydroxypropi®phenone (XIII), mp 158-1590 is filtered; EXAMPLE 8.



  2.5 g are dissolved. of D-pñitrophenyl- 0 (-acétam5.no -hydroxypropiephên ne (XIII) at pf 142-144 C, (jD +22 5 (c = +2; ethanol), in 20 cn of ethanol and 75 cé of N-ethyl- piperidine After a few minutes, as proof of the completion of the

 <Desc / Clms Page number 10>

 
 EMI10.1
 racemization. D, h-p.nitronhenyl- p -acetamino- / 8 -hydroxypropiophenone (XIII) begins to separate as small yellow crystals.



  After 3 hours, they are collected to wash them with a little ether. The
 EMI10.2
 p ef. is 16C-lô3 C.



  EXAMPLE 9.



  2.5 g of D-p.:itrcphenyl- -acetamino- / 113 -hydroxypropiophenone (XII) are dissolved at m.p. 142-14 C, (4: <) D = +22 5 (c = 2; ethanol), in 25 cm3 of piperidine. An intense red color appears; after 5 minutes, poured into 100 cm3 of concentrated HCl and 100 g of; 1; Le. It separates from
 EMI10.3
 small yellowish crystals of D.l.-p.itrophellyl- -acetamino-9 -hydroxy-propiophenone (XIII); they are collected for drying, m.p. 164-166 C. TEMPLE 10.
 EMI10.4
 



  2.5 of Dp .ni trophenyl- 0 (-acetami '10 - 4 -hydroxypropiophenone (XII) at mp 142-144C (o () D = + 22 5 (c = 2; ethanol)) are dissolved in 140 cm3 d absolute ethyl alcohol; then they are added cold to 10
 EMI10.5
 cm3 of a solution of sodium ethoxide in ethanal (obtained by dissolving 0.25 g of sodium in 100 cm3 of ethanol). An intense red color appears. right now; after 5 minutes, neutralized with acetic acid; the ethanol is evaporated off in vacuo and purified by crystallization in
 EMI10.6
 dioxane. There is thus obtained D .L-p.ni trophenyl- O (-acetamino- -hydroxypropiophenone (XIII), mp 162-163, eg. EXAMPLE 11.



  5 '- of D-p.uitrophenyl- O {-propionamino- / 4 -hydroxypropiophenone (XII) is dissolved at m.p. 135-136 C, (eC) D = -265 (c = 4; ethanol). in 30 cm3 of piperidine at room temperature. After 5 minutes, poured into 100 cm3 of concentrated HCl and 100 g of ice. The D, L-p.nitrophenylc <-propionamino-9 -hydroxy-propiophenone (XIII), separates in the form of a glue which crystallizes immediately. We collect, and we dry; m.p. 115-116
EXAMPLE 12.
 EMI10.7
 



  4 g of Dp.nitrophenyl- 0 (-chloroacetamino-S '-hydroxypropiophenone (XII) at mp 101-102OC () D = -F6.4 (c = ..; acetone) are dissolved in 25 cm3 of pyridine at room temperature When the optical rotation has disappeared, the mixture is poured into 75 cm3 of concentrated HCl and 100 g of ice.
 EMI10.8
 p.nitrophenyl- -chloroacetamino- / 3 -hydroxy-propiophenone (XIII) separates; m.p. 128-130 C EXAMPLE 13
 EMI10.9
 3 g of D-p..nit: rophenyl- 0 <-benzamino- / -hydroxypropiophenone (XII) are dissolved at m.p. 149-150 C, () D = + 6O (c = 2; acetone), in 30 cm3 of piperidine; at room temperature. After 10 minutes, poured into concentrated HCl with ice added.

   It separates itself from small cris-
 EMI10.10
 level of D.L-poni trophenyl-O (-benzamino: f3 hydroxy-propiophenone (XIII); mp 157-159 C.



    EXAMPLE 14.
 EMI10.11
 



  15; of L - (+) - 1-p, nitrophenyl-1,3-diacetox3.-2-amLnopropano-hydrochloride (II) which, when purified in methanol and ether, exhibits a m.p. of 170-172OC. and (O <} D = + Ó 5 (c = 4.18; methanol), obtained as in Example 3 in 60 am 3 of water and basified with 5 g of sodium bicarbonate to give L - (-) - 1-p.nitrophenyl-2-acetyla-

 <Desc / Clms Page number 11>

 
 EMI11.1
 mino-3-acetoxy-propan-1-ol (IIZ) which, once purified in ethyl acetate, melts at 134-136 C; (o () D = - 19 7 (c = 3.86; methanol).



  12.6 g of L-threo-1-p.nitrophenyl-2-acetamino-3acetoxy-propan-1-ol (III) are dissolved in 110 cm3 of acetic acid, which is added at 15 ° C. a solution of 9 g of chromic anhydride, dissolved in 9 cm3 of water and diluted with 5 g of acetic acid. It is still left to stand for 3 hours at 15 C; then the excess chromic anhydride is removed with sodium bisulphite solution. The acetic acid is evaporated off in vacuo, the residue is taken up in water and extracted with chloroform.
 EMI11.2
 evaporation of the chloroform solution gives Dp.nitro- 0 <-acetamino- -acetoxy-propiophenone - (IV), which, crystallized again from ethanol, melts at 140-141 C (<! <)? = - 37 (c = 5.0; methanol).



  50 g of D - '; nitro, o-acetylamino - / "9 -acétoxypropiophenone (IV) are dissolved in 190 cm3 of ixàethanol, they are added to 10 e 3m of 0.5% sodium alcoholate (5 g of metallic sodium dissolved in 100 cm3 of absolute methyl alcohol), After 4 days and at room temperature the optical rotation of the solution disappears.

   Then added 10 cm3 of acid, 1.3% aqueous acetic and concentrated to half volume; then poured into 800 cm3 of ice water, which causes crystallization
 EMI11.3
 tion of p: nitro- o (-acetamino-acrylophenone (V); this, after further crystallization from ethanol, appears as small yellow prismatic needles, with m.p. 120-121 C.
 EMI11.4
 If D-p.nitra- -acetamino7 / 9-acetoDcy-propiophenone (IV) is reacted with 5 parts of pyridine at room temperature, the reaction is already completed after 18 hours. All you have to do is pour the
 EMI11.5
 everything in a mixture of concentrated HCl and ice, so that the p.nitro-O (-acetamino-acrylophenone (V) crystallizes.



  50 g of cold p, nitro-acetamino-acrylophenone (V) in 10 cm3 of dioxane, containing 24 g of gaseous HCl per 100 cm3 of dioxane. After one night, we pour into the water, which causes the
 EMI11.6
 crystallization of D, L-p.nitro- 0 (-acetaminol9-chloropropiophenone (VI); this, after a further crystallization in ethanol, takes the form of small white needles, which decompose at their m.p.
 EMI11.7
 



  120-120.50C.



  5 g of D, L-p.nitro-O <'-acetamino-Achloro-propiophenone (VI) (VI) are suspended in 25 cm3 of methanol. 0.31 g is added. of boron hydride and sodium at 71.3%. dissolved in 5 cm3 of me ± hanol. A brown solution is obtained which, diluted with water, allows the medium to crystallize.
 EMI11.8
 mixture of D, L-threo- and erythro-1% ponitrophenyl-2-acetamino-3-Chloro-propan-. 1-ol (VII), at m.p. 133-140 C. By fractional crystallization of this mixture in methanol, the less soluble derivative is first obtained, that is to say
 EMI11.9
 D.L-threo-1-p.nitrophenyl-2-acetamino-3-chloro-propan-1-ol. at m.p. in69-170C; D, L-erythro-1-p.nitrophenyl-2-acetamino-3-chloro-propan-1-ol is then extracted from the mother liquors, at m.p. 153-154C.



  The D, Lp.nitro-o <.e -acetamino - chloropropiophenone (VI) can also be reduced with lithium aluminum hydride, in the following way 5.0 g of chloroketone (VI) are dissolved in 50 cm3 of anhydrous tetrahydrofura-- which is added at a temperature of 40 C and with stirring,
 EMI11.10
 for 30 minutes, of a. solution of 0.20 g of H4AlLi in 20 ml of anhydrous tetrahydrc - -, ne. After a further period of 30 minutes, and still at 40 c, 5 cm3 of water are added and the precipitated lithium and aluminum hydroxides are separated by filtration.

   The hydroxide residue is then extracted with boiling methanol; then the two solutions together, in
 EMI11.11
 methanol and tetrahydrofuran, leave by Evorato. a mixture of D, L-threo- and erythro-1-panitrophenyl-2-acetamino-3-ehloro-propan-1-ol (VII).

 <Desc / Clms Page number 12>

 
 EMI12.1
 50 g of D, L-thrdo-pni-trophenyl-2-acetamino-3-chloro-propan-1-ol (VII) are dissolved in 150 cm3 of ethanol, and treated with 10 cm3 of NaOH. overnight, it is acidified to pH between 5 and 6; the ethanol is evaporated off and the residue dissolved with water.

   The solution is then extracted with ethyl acetate which, by evaporation, leaves crisp.
 EMI12.2
 tallize D.L-threo-1-p <.nitrophenyl-2-acetaoiino-1,3-propanediol (TIII); the latter, after a new crystallization in water, melts at 165-1660C.



  4.0 g of DL-erythro-1-ponitrophenyl-2-acetamino-2-chloro-propan-1-ol is dissolved in 110 cm3 of ethanol and added to 3.5 cm3 of NaOH - 5N. Boil for 5 minutes at reflux, and then stand for 2 hours. The precipitated NaCl is separated by filtration and
 EMI12.3
 evaporates the ethanol, to crystallize the D, L-erythro-1 - p.nitro-phenyl-2-acetamino-1,3-propandiol (VIII) which, crystallized again in ethanol,
 EMI12.4
 background at 192-1930C.



   3.3 g of the mixture of D, L-threo- and erythro-1-p.nitro-phenyl-2-acetamino-3-chloro-propan-1-ol (VII) are dissolved in 30 cm3 of methanol;
 EMI12.5
 adds, at the boiling point, 12 cm3 of NaOH / Nil. and let stand overnight. After evaporating off the methanol, the mixture is extracted with ethyl acetate and crystallized from water by fractional crystallization.
 EMI12.6
 the mixture of D.L-threo- and erythro-1-p.nitrophenyl-2-acetamino-1,3-propandiol (VIII).



  63 g of D, L-erythro-1-ponitrophenyl-2-acetamino-1,3-propanediol are suspended in 130 cm3 of chloroform, and they are added, with stirring, to 30 cm3 of thionil chloride, while maintaining the temperature at 25-30 C. The mixture is stirred for a further 30 minutes, still at 25-30 C., and filtered. A crude product is obtained which is purified by boiling it with 700 cm3 of methanol; after cooling, we fil-
 EMI12.7
 be cyclic D, L-erythro-1-p.nitrophenyl-2-acetamino-1,3-propanol-sulfite, â. m.p. 143 C (deci) ...



  In a small flask, 50 g of D, L-erythro-1-panitrophenyl-2-acetaminophen-1,3-propaneol is melted, heating in an oil bath maintained at 150 C. When melting is complete, the heating is stopped and the residue is dissolved in boiling ethanol.



  Cooling crystallizes D, L-threo-2-methyl-4-oxymethyl-5-p.
 EMI12.8
 nitrophenyl-a 2-oxazoline, which, when purified with ethanol, melts is 161-16200.



  Heated to 50-60 C. 50 g of D, h - threo-2-methyl-4-oethyl-5p.nitrophenyl-a2-oxazoline, with 220 cm 3 of H01 NII. The solution is treated with carboraffin and, after cooling, 20 g of sodium bicarbonate are added. D.L-threo-1-p.ni- is then crystallized.
 EMI12.9
 trophenyl-2-acLtamino-1,3-propandiol, m.p. 164-16500 (in water).



  20 g of DoL-threo-1-ponitrophenyl-2acétamino-1,3-propanàioi are heated in a water bath with 60 cm3 of 1C% HCl. It is decolorized with carboraffin, and the medium is made alkaline, at pH 11, with NaOH 36 Be.



  D, L-threo-1 -p.nitrophenyl-2-amino-1,3-propandiol (IX) crystallizes; after purification with water, its mp is 140-14l Co EXAMPLE 25.



  54.0 ci of L-threo-1-p.niù-ophenyl-2-amino-1,3-propandiol (I) are dispersed in 100 cm3 of dioxane and 100 cm3 of pyridine. Cooled to +5 C, and 60 cm3 of benzoyl chloride are added, while maintaining
 EMI12.10
 the temperature between t5 and - <- 10C. We keep everything overnight in a refrigerator; then poured, with stirring, into 200 cm 3 of concentrated HCl and 400 g of ice. Filtered and washed with water, then crystallized again.

 <Desc / Clms Page number 13>

 calf in ethanol, obtaining L-threo-1-p.nitrophenyl-2-benzamino-3-benzoxy-propaii-1-ol (III) at m.p. 173-174 C. (Ó) D = +23 3 (c = 2; CHC13).



   41.0 g of L-threo-lp.nitrophenyl-2-benzamino-3-benzoxy-propan-1-ol (III) are dispersed in 335 cm3 of acetic acid, 11.6 g of acetic acid are added. Chromic anhydride, dissolved in 12 cm3 of water. After 3 hours, 32 cm3 of sodium bisulfite are added to 32 Bé and 340 cm3 of water. We thread-
 EMI13.1
 then be Dp.nitro - benzamino - benzoxy-propiophemone (IV) oi, after recrystallization in methanol, melts at 145-14 "oc. 0 (o () D = -22 9 (c = 2, 0 ; methanol).



  Or dissolve 5.0 of Do (-benzamino- -benzoxy-ponitropropiephenone (IV) at mp 145-146 C and (0 () D = -22 9 2.06 methanol) in a mixture of 60 cm3 of chloroform and 60 cm3 of ethanol; 3.5 cm3 of 0.5% sodium alcoholate (5g of metallic sodium, dissolved in 100 cm3 of absolute ethyl alcohol) are added. After 24 hours, 3.5 cm3 of acid are added
 EMI13.2
 1.3% aqueous acetic and concentrated in vacuo, pqu'à dry residue.



  The residue is taken up in ethanol and the p.nitro-o (-benzamino-acrylophenone (V) which, after crystallization in methanol, melts at 135-137 C.
 EMI13.3
 5.0 g of p.nitro- -benzamino-acrylophenone (V) are dissolved in 10 cm3 of dioxane, containing 20 g of gaseous HCl in 100 cm3 of dioxane. After one night, poured into water, then crystallized.
 EMI13.4
 in methanol, D, L-p, nitro-a'-benzaminoy3 -chloropropiophenone (VI) at m.p. 144-146 C (dec.).



  OZ suspends in methanol. 5.0 b of D.L-ponitro-o (-benzamino- ss -chloro-propiophenone (VI) with 0.25 g of boron hydride and sodium at 73%. Diluted with water in which a mixture crystallizes.
 EMI13.5
 of D, L-thr3'o- and erythro-1-p.nitrohenyl-2-benzamino-3-ehloro-propan-1ol (VII) at m.p. 90-145C; the latter is dissolved in thanol and treated with 1.5 equivalents of 2N NaOH. After one night, ethanol is removed, and the mixture of D, L-threo and is crystallized. ethyl-1-p.nitrophenyl-2-bonzamino-1,3-propandiol (VIII), which gives, by fractional crystallization from etrarol, D, L-erythro-lp.nitrophenyl-2-benzamino-1,3propandiol .at mp 210-211 C, the latter being less soluble; finally, from the mother liquors, we obtain the DL-thre> * o-1-p., -, Itrophenyl-2-benza-ano-1,3-, oropandiol, at pofo 157-1jl C.



    (The reduction of DL-p.-nitro- -benzamino -chloro-propiophenone (VI) can also be carried out with aluminum isopropylate. To this end, 5.0 g of chloroketone is heated with 8 g of isopropylate. a-luminium in 125 cm3 of isopropanol, so as to distill,% through a rectification column, the acetone which forms during the reaction.



  When the acetone distillation is complete, the mixture is cooled and 45 cm3 of 2N sulfuric acid are added. and in addition, 200 cm3 of water. A precipitate then forms which is extracted with ethyl acetate; then, by eva-
 EMI13.6
 poration; from the latter, the crude D, L-1-p.nîtro-phenyl-2-benzRmino-3-chloro-propan-1-ols (VII) are obtained, which are subjected as such to the treatment with the caustic alkalis).



   20g of D, L-erythro-lp.nitrophenyl-2-benza-mino-1,3-propandiol are suspended in 100 cm3 of chloroform and 10 cm3 of SOCI2 are added at a temperature between + 5 and +10 C. After overnight at room temperature, with stirring, the cyclic sulphite of
 EMI13.7
 D, L-erythro-1-p.nitrophenyl-2-benzamino-1,3-propandiol, m.p. 177-17j <> C (dec.).



   23.0 g of D, L-erythro-1-p cyclic sulfite are melted. nitrophenyl-2-benzamino-1,3-propandiol and, after cooling, they are added with 106 cm3 of 20% HCl. boil at reflux for 12

 <Desc / Clms Page number 14>

 hours, then the aqueous solution is washed with ethyl ether, the mother liquors are evaporated under vacuum, then taken up in 60 cm3 of water, and
 EMI14.1
 makes them alkaline ap5 11 with taCN at 3o Bé. The D.L-threo-1-ponitrophenyl-2-amino-g 1,3-propandiol (IX) is then filtered which, after further crystallization in water, melts at 140-141 ° C. EXAMPLE 16.



  5.0g of p.nitro-acetamino-acrylophenone (V) is dissolved cold
 EMI14.2
 in 10 em3 of dioxane, containing 21 g of EBr in 100 cc. After one night, poured into water and filtered the D, Lp.nitro- 0 (-acetamino-jS -bromopropiophenone (VI) which crystallizes; purifies in ethacl, it is in the form of needles at mp 1680C (dec.); reducing the D, T - panitrc- o (- acetamino-ss -bromopropiophenone (VI) with boron and sodium hydride, in a manner analogous to that described in the preceding examples, then we
 EMI14.3
 reacts the resulting mixture of D, L-threo- and erythro - 1-ponitrophenyl-2-acetamino-3-bromo-propan-1-ol (VII), with NaOH in a solution of water and ethanol, always d 'in a manner analogous to what has been described above.



  One then separates, by fractional crystallization, the D, L-threo- and ery-
 EMI14.4
 thro-1-p, nitrophenyl-2-acetamino-1,3-propandiols (VIII), lejoomposé erythro being less soluble than the other.



   CLAIMS.



   1. - Process for the conversion of D- and / or L-threo- and / or
 EMI14.5
 erythro-1-phenyl- or 1-ponitrophenyl-2-amino-1> propanediol in D, L-threo-1-phenyl- and 1-ponitrophéiiyl-2-amino-1,3-propandyol respectively; charac- terized by the fact that the compound to be converted is transformed, by means of reactions which eliminate at least one of the asymmetries of the chain of the starting compound, into an optically inactive compound, on which the original chain is reconstructed which is epimerized eventually.


    

Claims (1)

2. - Process according to claim 1, for the conversion of D- and / or L-threo- and / or erythro-1-phenyl and 1-p-onitrophenyl-2-amino-1.3-propandiol, respectively, to DL- threo-1-phenyl- and I-ponitrophenyl-2-amino-1,3-propandiol respectively; based essentially on the fact that EMI14.6 N-acylo derivatives of D- and L-threo- and erythro-1-phenyl or 1-p.nitrophenyl-2-amino-1,3-propandyol are transformed into D- and L- cl (-acylamino- ss Respective hydroxy-propiophenones, which in turn are racemized, to be converted to the corresponding diols, by known methods. 3. - Process according to claims 1 and 2. based essentially on the fact that the N-acylaminodérivé D- and L-threo- and erythro- EMI14.7 1-phenyl or 1-p.nitrophenyl-2-acylamino-1,3-propardiols are oxidized directly and selectively, treating them with halogens or with compounds which liberate halogens, in aqueous solution and at a low rate. temperature between 0 and 150 C preferably in the presence of ac- EMI14.8 tinic, in order to obtain the D- and 1-0 (-acylamino- / 3 -hydroxy-propiophenones, or the D- and Lp.ni-tro- -acyl.amino - /, 3 -hydroxy-propiophenones respectively . 4. A method according to claims 1 to 3, based essentially on the fact that the halogen employed is bromine, or the compound which releases the bromine is an alkaline bromate. 5.- Process according to claims 1 to 4, characterized in that sodium bromate is used. 6. - Process according to claims 1 to 5; characterized by lefait that one operates in the presence of hydrobromic acid. <Desc / Clms Page number 15> 7. A process according to claims 1 to 6, based essentially on the fact that the D- and L- Ó-acylamino-ss-hydroxypropiophenones or the respective p.nitro-derivatives are racemized by treating them, at temperatures between 0 and 60 C with substances having a basic function. 8. A method according to claim 7, characterized in that said substances with a basic function used are inorganic compounds, such as Sonder tapotasse, etc ... or organic compounds, such as primary amines, secondary or tertiary, cyclic, heterocyclic or aliphatic, or alkali alcoholates and enolates, alkali salts of organic acids, or organometallic derivatives of alkali metals. 9. - Process according to claims 7 - 8, characterized in that 1.'on uses pyridine as substance with a basic function, under anhydrous conditions. 10, - Process according to claims 7 - 8, characterized in that one employs N-ethyl-piperidine as substance with basic function, under anhydrous conditions. 11. - Process according to claims 7 - 8, characterized in that one employs piperidine as substance with basic function, under anhydrous conditions 12. - Process according to claims 7 - 8, characterized in that an alkaline bicarbonate, preferably sodium bicarbonate, in aqueous solution is used. 13. - Process according to claim 1, for the conversion of D- and / or L-threo- and / or erythro-1-phenyl- or lpnitrophenyl-2-amino-1,3-propandyol enD.L-threo -1-phenyl- or 1-p.nitrophenyl-2-amino-1,3-propandiol respectively; essentially based on the following series of reactions: Optionally substituted D - to L-Ó-acylamino-ss-acyloxy-propiophenones EMI15.1 (R being equal to or different from R '= alkyl, haloalkyl, aryl, aralkyl), obtained by known means from the aforementioned aminodiols, are transformed into the corresponding Ó-acylamino-acrylophenones EMI15.2 (R having the meaning mentioned above); and these are converted into the corresponding D.L- Ó-acylamino-ss-halo-propipophenones EMI15.3 (where X = CI, Br or J, and R has the same meaning as above); which are then reduced to D, L-threo and D, L-erythro-1-phenyl or l-p.nitrophé <Desc / Clms Page number 16> EMI16.1 nyl-2-acylamino-3-halo-propan-1-ols corresponding respectively EMI16.2 (where X and R have the same meaning as above); which are conver- EMI16.3 tis in D, L-threo- and D, L-erythro-1-phenyl- or 1-p., nitrophenyl-2-acylamino-1,3-propandiols respectively EMI16.4 (where R has the same meaning as above) that we can finally transform EMI16.5 me, according to known methods, in D, L-threo-1-phenyl-and 1-p.ni-trophenyl-2-amino-1,3-propandiol, respectively. 14.- A method according to claim 13, characterized by the EMI16.6 makes that 64 -acylâmino-acrylophenolles and p.nitro- 0 (-acylaminoacrylophenones (V) are obtained from 0 (-acylamino- -acyloxy-propiophenones and p.-nitro- Ó -acylamino- ss - acyloxy-propiophenones (IV) respectively, by means of an elimination reaction, catalyzed by substances with a basic function, such as soda, potash, etc., or by organic substances, such as primary amines secondary or tertiary cyclic, heterocyclic or aliphatic, alkaline alcoholates and enolates, alkali metal salts of organic acids, organometallic derivatives of alkali metals, preferably at ambient temperature. - Process according to claim 14, characterized in that pyridine is used as substance with a basic function. 16. - Process according to claim 14, characterized in that one employs traces of sodium alcoholate as substance with a basic function. 17. - Process according to claims 13 and 14. characterized EMI16.7 in that the 0 (-acylamino-acrylophenones and p.nitro- 0 (-acylamino-acrylophenones (V) respectively, are reacted with a hydrohalic acid, such as HCl, HBr or HJ, dissolved in a ether, such as ethyl or propyl ether, tetrahyclrofuran, dioxane, etc. * .. ,, in anhydrous condition, and at varying temperatures between 0 and 100 C for EMI16.8 obtain the D, L- α -acylamino- and the D.L-p.nitro- 0 <-acYlamino -halogenopropiophenones (VI) respectively. 18. - The following process, claims 13 to 17, characterized by ' EMI16.9 the fact that D.L- ot. acylamino- and D, L-ponitro- o (-acylamino-jt1- halogeno-propiophenones (VI) respectively, are reduced with metal hydrides, so as to transform the ketone group into an alcohol group. EMI16.10 lic, giving D, L-threo- and D, L-er.% thro-1-phônyl- and 1-p.nitrophenyl-2-acylamino-3-halogeno-propan-l-ols (VII) respectively . 19. - Process according to claims 13 to 18, characterized in that the metal hydride used is that of boron and sodium, or of boron and potassium, in aqueous or alcoholic solution, or of water and alcohol . <Desc / Clms Page number 17> 20. - Process according to claims 13 to 18, characterized in that the metal hydride used is that of boron and lithium or lithium and aluminum, in ethyl ether or tetrahydrofuran solution. 21. - 'Process according to claims 13 to 18, characterized in that the reducing agent'employed is an aluminum alcoholate in the presence of an excess of alcohol, for example aluminum isopropylate in isopropyl alcohol. 22. - Method according to claims 13 to 21, characterized EMI17.1 in that the D, L-threo- or DL-erythro-1-phenyl- and 1-p.nîtrophenyl- 2-acylamino-3-halogeno-propan-1-ols (VII) are reacted in alcoholic solution , with an alkaline hydrate (NaOH, KOH, etc.) cold for 10 to 15 hours, or else hot for 5 to 30 minutes, in order to replace the halogen with the oxhydril; so as to obtain the D, L-threo- or the EMI17.2 D, L-erythro-1-phenyl-and -I; p.nitrophenyl-2-acylamino-1,3-propandiols (VIII) respectively. 23. - Any process which combines, in any of the ways indicated in the diagram of the description, process phases according to the preceding claims, to obtain D, L-threo-1-phenyl- or 1- p. nitro-phenyl-2-amino-1,3-propandiol, starting from D- or L-, erythro- EMI17.3 or threo-1-phenyl or 1-panitrophenyl-2-amino-1,3-propandyol, respectively. 24. - The method of claim 1, which uses all or part of the operations described in the examples. EMI17.4 25. - D, L-threo-1-phenyl-2-aminopropanediol, obtained by a process according to one or more of claims 1 to 21. 26. - D, L-threo-1-p.nitrophenyl-2-amino-1,3-propandyol, obtained by a process according to one or more of claims 1 to 24.