FR2632642A1 - NOVEL DIOXANIC DERIVATIVES THAT CAN BE OPTICALLY ACTIVE, THEIR PREPARATION METHOD AND APPLICATIONS - Google Patents

Abstract

The dioxane-1,3 ones-4 of the invention may carry different substituents, in particular hydrocarbonated substituents, in positions 2, 5 and 6; in particular, derivatives carrying a functional group in 5 are highly attractive. The preparation comprises condensation of a beta -hydroxy carboxylic acid with an aldehyde, ketone or acetal. Application: production of beta -hydroxylated amino-acids.

Description

 The present invention relates to novel dioxane derivatives. It also includes a process for the preparation of such derivatives, as well as applications thereof.

 Dioxanes are used as solvents. The present invention widens their field of applications by the introduction into the molecule of another function and in general also of various substtuants. This happens to compounds which can be useful, for example as perfume fixatives, foam additives, paint thinners, cosmetic compositions, biocides, maintenance products, etc. A particularly interesting application is their use as starting material for the preparation of hydroxylated amino acids.

où les symboles R à R6 désignent, indépendamment les uns des autres,des atomes d'hydrogène ou des groupes hydrocarbonés pouvant d!ailleurs porter des substituants, en particulier des halogènes, hydroxyles, carboxyles ou/et groupes amino, sont caractérisés en ce qu'au moins R1 est un hétéroatome ou un atome ou groupe fonctionnel.The dioxane derivatives according to the invention, which can be optically active, are

where the symbols R to R6 denote, independently of one another, hydrogen atoms or hydrocarbon groups which can, moreover, carry substituents, in particular halogens, hydroxyls, carboxyls and / or amino groups, are characterized in that 'at least R1 is a heteroatom or an atom or functional group.

 When one or more of the groups R2 to R6 are hydrocarbon radicals, these are preferably α-liphatic in C1 to C18, aryl in C6 to C10, or / and aralkyl or alkaryl in C7 to C28. In the compounds according to the invention, the most common, R2 and R3 are atoms of H, while R4, R5 and R6, similar or different, meet the definition given above.

Other more common compounds are those, in which only one or two of R2 to R6 are hydrocarbon groups, the others being H, or are they all hydrogen atoms. Thus, the simplest products according to the invention correspond to the formulas

 Non-limiting examples of these dioxanones are compounds according to formulas (2) to (4), in which the R4 and R5, which are similar or different, are -CH31 -C2H5 - C3H7 -C4H9, -C5H111 -C6H13, -C6H5, -C6H4-CH31 -CH2-C6H5, -CH2, -CH2-CH2-CH2-C6H5, -C6H11 (cyclo), -CH = CH2, -CH-CH2 = CH2 etc.

diazo -N=N-, thiol -S-, thiol -SH, sulfono S03H, tosylate, phosphate, phosphite, phosphine, phosphinate ou sélenio -Se-.The atom or functional group R1 can be a halogen, F, Cl, Br or I, an -N02, -NH21 hydroxylamino -NH-OH, hydrazo-NH-NH-, hydrazino-NH-NH2 azido carbamato

diazo -N = N-, thiol -S-, thiol -SH, sulfono S03H, tosylate, phosphate, phosphite, phosphine, phosphinate or selenio -Se-.

 The substituted dioxanones1 according to the invention can be prepared by the action of a carbonyl compound on a 5-hydroxy carboxylic acid. There are two ways to achieve this goal.

1 - The ss-hydroxy carboxylic acid used carries in cK one of the groups R1 mentioned above. The carboxylated compound being an aldehyde, a ketone or an acetal, the reaction can be diagrammed as follows

For example, starting from a chlorinated acid in α (R1 = Cl), a dioxanone (6) chlorinated in position 5 is obtained.

ou sous celle d'un acétal

où R7 est un alkyle, en particulier méthyle, éthyle ou propyle.The carbonyl compound R5R6CO can be taken in the form of its hydrate

or under that of an acetal

where R7 is alkyl, in particular methyl, ethyl or propyl.

 The hydroxycarboxylic acid carries in or a hydrogen atom, that is to say R1 = H; reaction (6) then gives a dioxanone having, on the carbon in position 5, at least one H. In this case, according to the process of the invention, this hydrogen or the desired group R1 is substituted in this an operation subsequent to the preparation of dioxanone. This substitution is carried out in the presence of a base, at low temperature, by the action of a compound of the atom or group R1, in particular R1Y where Y denotes a leaving group, which can for example include a halogen, carboxyl , ester, carboxylic amide, sulfonate, phosphate, phosphinate or the like.

So we have the reaction

Amines, organometallic compounds, in particular those of alkali or alkaline-earth metals, hydrides or amides of such metals, for example Li amides, such as diisopropyl amide, are suitable as bases.
Li or Li hexamethyl disilamide.

 The groups R1 to R6 having the meaning given above, the reaction can be carried out with a wide choice of aldehydes and ss-hydroxy carboxylic acids. For the preparation of the simplest dioxanones, formaldehyde or its polymers, acetaldehyde, propanal, butanal, iso-butanal, pentane, benzaldehyde, phenylpropanal, aldehyde hydroxybenzoSque, anisic, cinnamic or phenyl-acetaldehyde are used, for example.

(R1=H ou groupe selon la description quiprécède) employés suivant l'invention, peuvent être par exemple tels que les acides -hydroxy propionique, butyrique, valérique, caprolque, décanolque, phényl-propionique, phényl-butyrique, etc.Carboxylic acids

(R1 = H or group according to the preceding description) used according to the invention, can be for example such as hydroxy propionic, butyric, valeric, caprolic, decanolic, phenyl-propionic, phenyl-butyric, etc. acids.

and their isomers, as well as substituted derivatives, in particular halogenated, as * -hydroxy chloropropionic and homologous acids.

 The reaction (6) is preferably carried out in an inert solvent, which can in particular be a hydrocarbon, chlorinated hydrocarbon or ether dissolving at least one of the reactants. So we can use ben zene, -toluene, hexane, heptane, dichloromethane, dichloroethane, trichlorethylene, chloroform, dioxane, tetrahydrofuran, etc. Optionally, the excess of one of the reagents can serve as a solvent for the other.

 The preferred concentrations of hydroxy carboxylic acid in the solvent are generally between 0.1 and 1 mol / liter, and better still, between about 0.2 to 0.4.

 Although it is possible to use the reagents in stoichiometric proportions, it is useful to have an excess of one of the reagents over the other.

In general, the proportion of aldehyde or acetal relative to the hydroxy acid is of the order of 0.2 to 3 moles per mole of acid and preferably of 0.5 to 2 or, better still of 0 , 6 to 1.7.

 The temperature can vary between ambient and 1300C, but it is preferably of the order of 400 to 1000C; if necessary, that is to say when one or both reactants have a voltage of vapor above the atmospheric, at the chosen temperature, the operation is carried out under pressure.

 The reaction according to the invention being catalyzed by acids, it is carried out in the presence of one of the acids usually used in the art for this purpose, for example with benzene sulfonic acid or paratoluene sulfonic acid, optionally taken at state of their amine salts.

 Depending on the temperature of the reaction medium, depending on the nature of the reagents and that of the satalyzer, the reaction generally lasts about 0.5 to 7 hours, and most often 1 to 3 hours.

 The dioxanone formed can be recovered from the reaction medium by evaporation of the solvent and purification, optionally by crystallization.

 The 2nd mode of preparation of the substituted dioxanones according to the invention, which consists in effecting a substitution by means of a compound A1Y, according to the reaction (7) indicated above, is possible thanks to the lability of a carried bond by the carbon atom in position 5. This makes it possible to obtain various useful derivatives. Among others, mention may be made, for example, of halo or hydrazo derivatives in 5, capable of serving as starting material for the production of hydroxylated amino acids.

Thus the introduction of a halogen in R1-is achievable by the reaction of a dioxanone, whose
R1 is an H, with halogen, in organic solution, at a temperature below 00C, in the presence of a base
and preferably a small proportion of organometallic compound. New halogenated compounds are thus obtained.

 A hydrazo group can be attached to R1, in place of an H, by the action of an alkyl diaza-diformate (R8), R80CC-N = N-COOR8, on the dioxanone chosen, within d 'a solvent, in the presence of an organic base and / or an organometallic compound, at a temperature below OOC. The hydrazo dioxanones obtained can be transformed into the corresponding amino derivatives and used in the preparation of amino acids.

 The halogenated and hydrazo derivatives, which are discussed above, are particularly useful for the production of serine and threonine, the need for which is felt in the fields of food, pharmacy and products. cosmetics. Threonine is used in particular in the feed of backyard and livestock and its additive derivatives as an additive to fight certain respiratory diseases.

In a halogenated dioxanone, the halogen can be replaced by an NH2, for example by means of sodium azide NaN3 and subsequent hydrogenation; by acid treatment, in particular acetic treatment, the dioxanone-amine is hydrolyzed and gives rise to b- a hydroxylated amino acid:

The aldehyde or residual acetal R5R6CHO can also be recovered to be reused in reaction (6).

When R3 is CH3 and R4 = H, we are in the presence of the
D-allothreonine which is easy to convert into Lthreonine Interesting, in the manner known per se.

qui, par hydrogénation, conduit au chlorhydrate du e-hydroxy a -amino acide correspondant. Avec R3 étant
CH3 et R4=H, cet acide est le chlorhydrate de D-allothréonine dont la transformation en la L-thréonine est connue.Likewise 5-dioxanone, mentioned above, can be applied to the preparation of hydroxy amino acids. By treating the hydro-derivative, in solution, with an acid, for example HCl, the hydrochloride of ~ 2-hydroxy-3-hydroxy carboxylic acid is obtained.

which, by hydrogenation, leads to the hydrochloride of the corresponding e-hydroxy a-amino acid. With R3 being
CH3 and R4 = H, this acid is D-allothreonine hydrochloride, the transformation of which into L-threonine is known.

 The invention is illustrated by the following nonlimiting examples.

avec 6,75 g (75 mmol) de paraformaldéhyde (HCHOk et 50 mg d'acide paratoluène sulfonique comme catalyseur, le tout dans 150 ml de benzène sec.EXAMPLE 1
Preparation of (-) - 6-methyl-1,3-dioxane one-4 (formula 3)
In a balloon topped by a Dean device
Stark 4.6 g (45 mmol) of P-hydroxybutyric acid are introduced

with 6.75 g (75 mmol) of paraformaldehyde (HCHOk and 50 mg of paratoluene sulfonic acid as catalyst, all in 150 ml of dry benzene.

The mixture is brought to the boiling point of the solvent, with reflux, for 2 hours, the reaction being followed by 1 H NMR.

After this time, the medium is cooled to room temperature and diluted with 150 ml of ether; the ethereal solution is washed with an aqueous NaHCO3 solution, then with saturated NaCl.

d'après le spectre RMN
doublet 3H 1,3 ppm J-6,2 Hz
dd 1H 2,37ppm JH(1)H(2)=10Hz
JH(2)H(3)= 10 Hz
dd 1H 2,63ppm JH(1)H(2)=18 Hz
(1) (3)=4 Hz
H
m 1H 2,97ppm
d 1H 5,25ppm J (4) H(5)=5,5HZ
d 1H 5,34ppm
EXEMPLE 2
Préparation de diméthyl-2,2 méthyl-6-dioxane-1,3 one 4 (formule 1 où R1 à R3 sont des H et R4 à R6 des CH3).Evaporation of the solvent leaves a residue which is distilled under vacuum; the product, obtained with 66% yield, is a colorless liquid boiling at 350C under 0.1 mm Hç; ; its structure corresponds to

from the NMR spectrum
doublet 3H 1.3 ppm J-6.2 Hz
dd 1H 2.37ppm JH (1) H (2) = 10Hz
JH (2) H (3) = 10 Hz
dd 1H 2.63ppm JH (1) H (2) = 18 Hz
(1) (3) = 4 Hz
H
m 1H 2.97ppm
d 1H 5.25ppm J (4) H (5) = 5.5HZ
d 1H 5.34ppm
EXAMPLE 2
Preparation of dimethyl-2,2 methyl-6-dioxane-1,3 one 4 (formula 1 where R1 to R3 are H and R4 to R6 are CH3).

Using the same technique as in Example 1, 1 equivalent of hydroxy butyric acid is reacted with 1 equivalent of dimethyl acetal.

A colorless oil is obtained with a yield of 56%, which corresponds to the formula

whose 1H NMR spectrum is
doublet 3H 1.15 ppm
singlet 6H 1.55 ppm multiplet 2H 2.45 ppm multiplet iH 4.2 ppm (11)
EXAMPLE 3
Preparation of (phenyl-2-ethyl) -2 methyl-6 dioxane-1,3 one-4 (formula 2 with R4-CH3 and R5- CH2CH2C6H5, R = H>
As described in Example 1, 4.5 g (45 mmol) of ss-hydroxy butyric acid were reacted with 4 g (30 mmol) of 3-phenylpropanol, C6H5-CH2CH2CH2CHO, in 150 ml of dichloromethane, in the presence of 0.75 g (3 mmol) of pyridinium paratoluene sulfonate
CH3-C H -SO CHH The reaction mixture is brought
3 '55 at boiling point with reflux of the solvent (400C), and the progress of the reaction is followed in 1 H NMR, until the signal disappears at 9 ppm of the aldehyde.

The medium is then cooled, diluted with 150 ml of ether, and washed with a 5% aqueous solution of NaHCO3; this washing is carried out in three stages, each time with 10 ml of this solution. The separated organic phase is dried over MgSO 4 anh., Then it is filtered and concentrated in vacuo.

The product formed is purified by crystallization from an ether-pentane mixture. The yield of pure product is 3.6 g or 56% relative to the aldehyde used.

This product melts at 550C.

 Its [20 is -15.04 (c = 0.904 / CHCl3).

#a = 7,26 ppm (m,5H)
= 5,28 ppm (t,3 Hz 1H) #c = 3,99 ppm (qdd,1H H, JCh=6,06 Hz, 3J c=6
JCf=10,6 Hz) = = 2,81 ppm (t, 2 H, 3Jdg =4 Hz)
Se = 2,66 ppm (dd, 1 H,3Jec=4,4 Hz, Jef=13 Hz) = = 2,53 ppm (dd, t Jfc'tO,Hz, Jfe=13 Hz)
LJLe Hr 3 5 = 2,11 ppm (m, 2 H) ; 6h'1,32 ppm (d, 3 H, 3Jhe=6,06Hz)
Analyse calculée pour C 3Ht603
C = 70,9 ; H = 7,3
trouvée C =70,15 ; H = 7,36
EXEMPLE 4
Halogénation de la méthyl-6 dioxane-1,3 one-4 en méthyl-6 iodo-5 dioxane-1,3 one-4.NMR analysis gives

#a = 7.26 ppm (m, 5H)
= 5.28 ppm (t, 3 Hz 1H) #c = 3.99 ppm (qdd, 1H H, JCh = 6.06 Hz, 3J c = 6
JCf = 10.6 Hz) = = 2.81 ppm (t, 2 H, 3Jdg = 4 Hz)
Se = 2.66 ppm (dd, 1 H, 3Jec = 4.4 Hz, Jef = 13 Hz) = = 2.53 ppm (dd, t Jfc'tO, Hz, Jfe = 13 Hz)
LJLe Hr 3 5 = 2.11 ppm (m, 2 H); 6h'1.32 ppm (d, 3H, 3Jhe = 6.06Hz)
Analysis calculated for C 3Ht603
C = 70.9; H = 7.3
found C = 70.15; H = 7.36
EXAMPLE 4
Halogenation of 6-methyl-1,3-dioxane one-4 to 6-methyl-5-iodo-1,3-dioxane one-4.

The operation is carried out on the product (10) obtained according to Example 1.
0.154 ml (1.1 mmol) of di-isopropylamine, 1 ml of solvent THF and 0.44 ml of a 2.5 M solution of -BuLi in hexane are introduced into a balloon dried under argon; the introduction takes place at OOC under argon.

After 15 min, the mixture is cooled to approximately -780 ° C. and 0.116 g of methvl-6 dioxane1.3 one-4 (1 mmol) dissolved in 1 ml of THF is added dropwise.

The reaction medium, thus formed, is added dropwise to a solution of 0.3 g of iodine '(1.18 mmol I2) in 1 ml of THF at -780C, well stirred.

After 5 minutes, 1 ml of aqueous 5% NH 4 Cl solution and 5 ml of ether are added.

est ainsi obtenue avec un rendement de 90%
EXEMPLE 5
Halogénation de la diméthyl-2,2 méthyl-6 dioxane-1,3 one-4 en diméthyl-2,2 méthyl-6 iodo-5 dioxane-1,3 one-4
L'opération est effectuée sur le produit obtenu suivant l'exemple 2. De manière analogue à celle de l'exemple 4, on obtient le composé

The mixture is allowed to warm to room temperature, then Na thiosulphate Na 2 S 203t is added to reduce the excess iodine, and the mixture is extracted with ether 3 times, each with 5 ml of ether. The organic phases are dried and evaporated; 6-methyl-5-iodo-1,3-dioxane one-4

is thus obtained with a yield of 90%
EXAMPLE 5
Halogenation of 2,2-dimethyl-6-methyl-1,3 dioxane one-4 to 2,2-dimethyl-6 methyl-5 iodo-1,3-dioxane one-4
The operation is carried out on the product obtained according to Example 2. In a manner analogous to that of Example 4, the compound is obtained

EXAMPLE 6
Obtaining the (2R, SRS, 6R) [iphenyl) 2 ') - ethylJ-2iodo-5 methyl-6 dioxane-1,3 one-4 from the dioxanone of Example 3.

The technique is the same as in Example 4, applied to 0.22 g of starting dioxanone (1 mmol). The iodized derivative is obtained with a yield of 90% on the dioxanone used. NMR confirms the following structure of the iodine derivative

1 H NMR (CDCi3, 80 MH3)
a = 1.55 (3H, d, J = 7 Hz)
b = 2.15 (2H, m); c = 2.9 (2H, m)
d = 4.4 (1H, m); e = 4.6 (1H, d, J = 8Hz)
f = 5.45 (1H, J = 5Hz); g = 7.4 (5H, s)
EXAMPLE 7
Preparation of a hydrazo-5 derivative of dioxanone from Example 1
In a flame-dried flask, under argon, a base is introduced, in particular 0.154 ml, ie 1, t mmol, of di-isopropylamine with 1 ml of anhydrous THF, and the medium is cooled to approximately -780C; 0.44 ml of a 2.5 M solution of n-BuLi (1.1 mmol) in hexane is then added thereto.

After 1 hour of stirring at the same temperature, a solution of 0.116 g of methyl 6-dioxane-1,3 one-4 (1 mmol) in 1 ml of anhydrous THF is added dropwise. After one hour of stirring, still at -780C, 0.23g (1 mmol) of tertiary butyl diazadiformate (CH3) 3C-OOC-N = N-COO-C (CH3) is added all at once. ) 3 in solution in 0.5 ml of THF.

An hour later we add
1 ml of a 5% aqueous NH4C1 solution.

The aqueous phase is extracted with ether (3 times 5 ml).

confirmée par la RMN H
singulet 1,40 ppm 18H (a) m 4ppm 1H(c)
d 1,47 ppm 3H (b) dd 4,4ppm et 4,3 ppm 1H(d)
deux doublets 2H 5,2 5,3 ppm J=5Hz
EXEMPLE 8
Préparation d'un dérivé hydrazo-5 de la dioxanone de l'exemple 3.The combined organic phases are washed with an aqueous solution, saturated with NaCl; they are dried over MgSO4-, filtered and concentrated in vacuo. The hydrazo-5 derivative is obtained with a yield of 95% relative to the starting dioxanone; he meets the formula

confirmed by H NMR
singlet 1.40 ppm 18H (a) m 4ppm 1H (c)
d 1.47 ppm 3H (b) dd 4.4ppm and 4.3 ppm 1H (d)
two doublets 2H 5.2 5.3 ppm J = 5Hz
EXAMPLE 8
Preparation of a hydrazo-5 derivative of dioxanone from Example 3.

 The same procedure as in Example 7 is applied to the (phenyl-2 'ethyl) -2 methyl-6 dioxane1,3 one-4 of Example 3.

The operation is carried out with 0.22 g (1 mmol) of this dioxanone, all the other conditions being those of the preceding example. The colorless oil formed is obtained with a yield of 95% on the dioxanone used.

Purified by chromatography, it has the following characteristics
Rf = 0.7 [α] D20 = +23.710 C = 2.59, CH2Cl2 eluent 1.5 AcOET, 1.5 hexane, 1% N (CH3) 3
1H NMR: 200 MHz ppm / TMS: 5a = 7.26-7.04 (m, 5H)
b = 6.43 (wide, 1H)
5 = 5.33 and 5.26 (t, 1H)
vs
#d = 4.41 and 4.28 (d, wide, 1H)
#e = 3.99 (dq, 1H) IR film (cm-1) = = 2.72 (t, 2H) γ = 3340
# g = 2.05 (td, 2H) <= 3020 (M) (Ar)
#g = 1.47 (d, 3H) y = 2980 (M) (CH)
#i = 1.40 (s, 18H) r = 1770 (F)
&gamma; = 1720 (F)

The irradiation at 500 MHz of the methyl protons (1.47 ppm) reveals a doublet at 3.99 ppm. 3HH = 10 Hz. This shows that the proton is trans with respect to Hd, so the dioxanone amino has the stereochemistry described in the following figure

 The protons Hd and H c present two distinct signals probably due to the existence of conformers around the C5-N bond.

EXAMPLE 9
Conversion of the halogenated compound (13) to the hydroxylated amino acid
To a solution of 0.242 g (1 mmol) of methyl 6-iodo-5 dioxane-1,3 one-4 (product 13 of Example 4) in 2 ml of THF, 4 ml of a methanolic solution containing 1 mmol of sodium azide NaN3; the mixture is brought to reflux for 24 hours. To the cooled solution is added 5% of palladium on barium sulphate and a stream of finely dispersed hydrogen is passed through for 24 hours.

After filtration, the solvent is evaporated off and the residue is taken up in 10% HCl, filtered again and evaporated.

By these treatments the iodine is eliminated and replaced by
NH2, the initial molecule (13) is cut between positions 1,2 and 2-3, and allothreonine hydrochloride is formed

After elimination of the HCl by treatment, at boiling, with a mixture of 10 parts of ethanol and 2 parts of propylene oxide, D-allothreonine is obtained which crystallizes, it is isomerized into L-threonine in the known way.

EXAMPLE 10
Conversion of the halogenated compound (15) to hydroxyamino acid
The operations of Example 9 are repeated on 0.346 g (1 mmol) of the iodized compound in 5 of Example 6.

#a= 4,5ppm(qd,1H,Jab=4HZ,
Jac=7Hz)
Sb=3,98ppm(d,1H,Jab=4Hz) #c=1,30ppm(d,3H,Jac=7Hz)
EXEMPLE 11
Transformation du composé hydrazo-5 de l'exemple 7 en
(5 -hydroxy aminoacide. The product obtained has the characteristics of
D-allothreonine: L] D20 = -8.26 (c = 1.15 / H2O)
NMR H 80 MHz D2 O
Ref. ext. TMS g (CH3) 4Si]

# a = 4,5ppm (qd, 1H, Jab = 4HZ,
Jac = 7Hz)
Sb = 3.98ppm (d, 1H, Jab = 4Hz) # c = 1.30ppm (d, 3H, Jac = 7Hz)
EXAMPLE 11
Transformation of the hydrazo-5 compound of Example 7 into
(5-hydroxy amino acid.

 1.4 g of the product (15), prepared in Example 7, are dissolved in 4 ml of anhydrous methylene chloride in a balloon dried under argon. The solution is cooled to 0 and 4 ml of trifluoroacetic acid are added dropwise. The medium is stirred at 0 ° C. to 200 ° C. for 3 hours, then the solvents are removed under vacuum. The residue is taken up in 10 ml of ethyl acetate and the organic phase is extracted using a 10% HCl solution (3 x 4 ml). The aqueous phase is concentrated in vacuo.

A very hygroscopic solid is obtained which is not purified for the next step.

This hydrochloride is introduced into a hydrogenating apparatus, with 5 ml of methanol and 500 ssl of acetic acid. 10 mg of platinum oxide are then added and the medium is stirred vigorously under an atmosphere of H2. When the stoichiometric amount dtH2 has been absorbed, the solution is filtered and the solvent is evaporated off. The solid product can be recrystallized from an ethanol, ethyl acetate mixture but can be used without purification in the following step. the ester of threonine hydrochloride, thus prepared, without purification, is dissolved in 8 ml of 6N HCl and brought to reflux for 1 hour. The solution is then evaporated in vacuo.

The product obtained is dissolved in 10 ml of anhydrous ethanol with 2 ml of propylene oxide, then brought to reflux for 15 minutes. The amino acid then crystallizes and is recovered by filtration.

For the D-allothreonine obtained we find the same spectrum
NMR as in Example 10. In addition [d3D = -9.54 (c = 2 / H2O) -1
IR (kir) 3100 cm (T wide)
-1
2050 cm (f)
1640 cm 1 (Ft
L-threonine is obtained from this product in the known manner.

EXAMPLE 12
Application of the hydrazo-5 compound of Example 8 (formula 17) to the preparation of t hydroxy amino acid.

 The operations of Example 11 are carried out starting from the compound (N, N'-ditertbutyloxycarbonyl) hydrazo-5 (2-phenylethyl) -2 methyl-6 dioxane-1,3 one-4 whose formula (17) and the characteristics are given in Example 8.

We end up, as above, with D-allothreonine.

EXAMPLE 13
Preparation and use of 2-methyl-1,3-dioxane one-4
According to the technique of example 1, 4.5 g (50 mmol) of acid * (5-hydroxy propionic acid) are reacted.
HO-CH2-CH2-COOH with 3.1 g (70 mmol) of acetaldehyde CH3CHO.

par la méthode de l'exemple 9.The 2-methyl-1,3-dioxane one-4 obtained (formula 4 with
R5 = CH3) is brominated as described for iodination, in Example 4. The brominated derivative at 6 is then converted into serine hydrochloride

by the method of example 9.

The serine is released from this hydrochloride by boiling its solution in a mixture of ethanol and propylene oxide.

Claims (16)

 1. Chemical consisting of a dioxane1,3 one-4 of formula

 where the symbols R2 to R6 denote, independently of one another, hydrogen atoms or hydrocarbon groups - which may carry substituents, in particular halogens, hydroxyls, carboxyls and / or amino groups, characterized in that at least one of the symbols R1, R2, denotes a heterogeneous atom or an atom or functional group.  2. Product according to claim 1, in which those of R2 to R6 which are hydrocarbon radicals are C1 to C18 aliphatic, C6 to aryl C10 or / and aralkyl or alkaryl C7 to C28.  3. Product according to claim 1 or 2,  2 3 characterized in that R2 and R3 are hydrogen atoms. NH2, hydroxylamino, hydrazo, hydrazino, carbamato, thio, thiol, or diazo, R2 being an H or a hydrocarbon group.  4.Product according to one of claims 1 to 3, characterized in that R1 is a halogen, a NO2, 7 t  5. Product according to one of claims 1 to 3, characterized in that R1 is a sulfonyl, tolyl-sulfonyl, phosphoryl, phosphite, phosphine, phosphinate or selenio group.  6. Process for the preparation of the product according to one of claims 1 to 5, characterized in that a t-hydroxy carboxylic acid which carries an atom or group R is condensed with an aldehyde, a ketone or an acetal according to claim 4 or 5.  7. Method according to claim 6, characterized in that the operation takes place in an organic solvent, in particular hydrocarbon or ether, the concentration of F-hydroxy carboxylic acid being preferably from 0.1 to 1M and the proportion of aldehyde, ketone or acetal being from 0.3 to 3 moles per mole of 5-hydroxy carboxylic acid.  8. Method according to claim 6 or 7, characterized in that the reaction takes place at a temperature between ambient and 1300C, and preferably between 400 and 1000C.  9. Process for the preparation of a substituted dioxanone, according to one of claims 1 to 5, characterized in that the dioxanone, of which at least one of the C atoms in position 5 carries a hydrogen atom, is treated within of a solvent, at low temperature, in the presence of an organic base, by a reagent capable of exchanging with this hydrogen the atom or group to be substituted.  10. Method according to claim 9, characterized in that a dioxanone is halogenated in position 5 by the action of a halogen in an organic solution, added with an amine and, preferably, a small amount of an organometallic compound, at around -780C.  11. Method according to claim 9, characterized in that a dioxanone is substituted in position 5 by a hydrazo group, by the action of an alkyl diazo-diformate, in an organic solvent, in the presence of 'an organic base and preferably a small amount of organometallic compound, at about -780C.  12. Method according to claim 9, characterized in that a dioxanone is aminated in position 5 by the action of sodium azide on a 5-halo dioxanone in organic solution and sub sequence hydrogenation of the solution.  13. Application of a 1,3-dioxane one-4 to the preparation of a 0 * -hydroxy or -amino acid, characterized in that a dioxanone, carrying an NH 2 in position 5, is subjected to the hydrolysis in a strongly acid medium, so as to cut the dioxanone molecule between positions 1-2 and 2-3, by releasing an aldehyde molecule.  14. Application according to claim 13, characterized in that the 5-amino dioxanone is obtained by the hydrogenation of a dioxanone carrying a hydrazo substituent in position 5.  15. Application according to claim 13 or 14, characterized in that the aldehyde, released by acid hydrolysis, is recycled to the preparation of dioxanone by the process of one or more of claims 6 to 12.  16. Product according to one of claims 1 to 5, characterized in that it is optically active.