1,3-di-(6,0-saharsa)-1,1,3,3-tetramethyldisiloxane and method thereof


(57) Abstract:

Usage: as an intermediate product for the synthesis of sweeteners. The essence of the invention: 1,3-di-(6-0-sucrose-1,1,3,3-tetrabutylammonium []20+34(CH3OH) from 0.31). Reagent 1:sucrose. Reagent 2: oxide dibulla. Reaction conditions: boiling methanol to obtain a clear solution. 2 C. p. F.-ly, 3 ill.

The invention concerns a method of obtaining derivatives of sucrose by rehospitalize reaction, and it can be used, for example, to obtain the monosubstituted derivatives of sucrose, in which the Deputy is in position 6. This invention also covers some new distano-okinawae connection.

Sucrose is a disaccharide having a molecular structure shown in Fig.1. (Of Fig.1-3 showing the molecular structure of sucrose and its derivatives, used conformational structural formula. For convenience in Fig.1 shows only the hydrogen atoms associated with carbon atoms in the two rings, and the number of positions of the carbon atoms). The sucrose molecule contains three primary hydroxyl group and five secondary hydroxyl groups. Sledovat may be sent only on a chemical reaction to obtain the desired hydroxyl groups. So, for example, artificial sugary substance 4,1',6'-trichloro-4,1',6'-tridyakisicosahedron obtained from sucrose by replacement of the hydroxyl at the 4, 1' and 6' positions of the chlorine. (In the process of getting a sugary substance stereoconfiguration in position 4 becomes therefore reverse the connection represents galactosucrose). This compound and methods of synthesis are described in U.S. patents NN 4343934, 4362869, 4380476 and 4435440. The direction of the chlorine atoms only and the desired position is the main problem of synthesis, especially in view of the fact that the hydroxyl group, which itemstats have different chemical activity (two primary and one is secondary; in addition, the synthesis is complicated by the fact that the primary hydroxyl, located in the 6 position is unsubstituted in the final product). Is this sugary substances is just one illustration of the synthesis of derivatives of sucrose, where it is desirable or education specific hydroxyl groups, and such groups or education only a certain number of hydroxyl groups, and probably in this latter case, the resulting hydroxyl group should not be specific hydroc the eskers, an example of implementation in an industrial environment monotomidae in the sucrose molecule.

The invention provides a method of synthesis of compounds of sucrose in the form of 6-substituted derivatives of sucrose in which the process is highly rehospitalized both in relation to the direction of the reaction is strictly in the 6-position, and get only mono-substituted derivatives. The term "regioselectively" refers to a reaction that is very conducive to getting only the main product. (See publication Hassner "Regiospecificity. The terminology used in the addition reactions of and elimination reactions", J. Org. Chem. 33, No. 7, 2684-2686, 1968).

In review publication called Regioselective manipulation of hydroxyl group via organotin derivatives, Tetrahedron, vol 41, N 4, pp. 643-663, 1985, David and others, describes the reaction of tin compounds with compounds containing a hydroxyl group, with the formation in stanasolovich compounds, which can then alkylaromatic or allroutes with the formation of simple or complex esters. Describes the response of the oxide bis(anti -) with different carbohydrates (including sucrose) followed by acylation to obtain a mixture slojnomu in reactions with hydrocarbons. This publication reported the receipt of two carbohydrate derivative dialkylanilines, namely 2,3-0-dibutylaniline derived methyl-4,6-0-benzylidene- -D-glucopyranoside and 4,6-0-benzylidene-2,3-0-dibutylaniline--D-mannopyranoside. The proposed molecular structure of these two Stanislavovich derivatives are shown in figures 3 and 4 on page 645 of this publication.

Wagner and others J. Org. Chem. 39, 24, 1974, describe getting dibutylaniline derivatives of nucleosides by reaction of the oxide dibutylamine with nucleosides in boiling methanol. After distillation of methanol stannylene derived alleroed by reaction with ravnovesnymi amounts of carboxylic acid and triethylamine.

Helzapfel and other "Derivatives of sucrose and selective benzoylation of the secondary hydroxyl groups of 6,1',6'-tri-0-trailigaz", S. Afr. Tydskr. Chem. 1984, 373, pages 57-61, describe the reaction of the oxide dibutylamine followed by reaction with benzoyl chloride, resulting 3-0-benzoyl-6,1',6'-tri-0-trailsource with the release of 72% and the derived 2-0-benzoate with the release of 9% and minor amounts of derivative 2,3'-benzoate.

As it says in well-known publications, the chemical activity of the hydroxyl group of the hydrocarbon is a priori to predict what hydroxyl group is activated (see page 646-647 shown as reference material the publication of the article David and others in the section "Stereoelectronic the communication sequence Sn-O-nucleophilic increased oxygen atom, especially the last paragraph of this section).

In Fig.1-3 presents the structural formula of sucrose, 1,3-di-(6-0-sucrose-1,1,3,3-tetrabutyl distannoxane, Saharsa-6-ether complex, respectively.

The method of the invention involves the reaction of oxide dibutylamine in boiling methanol with sucrose at a molar ratio of 1:1 during the time necessary to obtain a clear solution.

The following is a generalized description of the procedure.

In the reaction vessel are introduced methanol (100 ml), sucrose (5 g) and the oxide dibutyrate (of 3.64 g of 1 molar equivalent, per mole of sucrose is used for 1 mol of tin per mole of sucrose). The contents of the reaction vessel is boiled under reflux for 2-2,5 h, after which the methanol Argonauts. The product of this reaction is a 1,3-di-(6-0-Saharsa)-1,1,3,3-tetramethyldisiloxane (or dibutyltindilaurate "DBSS" in the form of a white solid.

In the described specific reactions oxide dibutylamine and sucrose are mixed and heated in boiling methanol. SL is methoxy-1,1,3,3-Tetra-butyldiethanolamine (or "dimethoxyphenoxy"). Dimethoxyphenoxy is such a compound that reacts with sucrose with the formation of the DBSS. Analysis of DBSS allows to conclude that DBSS is a compound of the following structure:

Suc-O-Sn(Bu)2-O-Sn(Bu)2-O-Suc, where Suc is a 6-0-sucrose (i.e. sucrose link is connected through oxygen, which is linked to the carbon atom in position 6), and where Bu represents butyl. In Fig. 2 shows the molecular structure of 1,3-di(6-0-Saharsa)-1,1,3,3-Tetra (hydrocarbon)-distannoxane, which are obtained by implementing the method of the present invention. This figure group "R" represent gidrolabilna group, which may be the same or different.

According to preferred principle of implementation of the present invention, when di(hydrocarbonate)-distannoxane is formed directly during the reaction of the oxide di(hydrocarbon) tin with the lowest alkanols, such as methanol, ethylene oxide di(hydrocarbon) tin and sucrose are used in this reaction is preferably in proportion to one mol of sucrose had no less than one mol of oxide di(hydrocarbon) tin. A slightly higher proportion of oxide di(guide the proportion of compounds of tin will reduce the amount of sucrose, turn in DBSS and, therefore, will reduce the specificity of the reaction.

Instead oxide dibutylamine can use other oxides di(hydrocarbon) tin, in which gidrolabilna groups associated with tin, can represent individually an alkyl, cycloalkyl, aryl or arylalkyl, such as methyl, ethyl, propyl, butyl, octyl, benzyl, phenethyl, phenyl, naphthyl, cyclohexyl, and substituted phenyl. Preferred hydratability groups are alkyl group with a content of up to 8 carbon atoms. Instead of tin oxide can be used dialkoxy, dihalogenide, diazelam di(hydrocarbon) tin and other ORGANOTIN compounds, which form a di(hydrocarbonate)distannoxane directly in the zone of the process.

This reaction is carried out in an organic liquid reaction medium which is a solvent sucrose and di(hydrocarbonate)distannoxane. When di(hydrocarbonate) distannoxane is formed directly in the zone of the process, the reaction medium preferably is a solvent for compound (or compounds) that are used to obtain di(hydrocarbonate)distannoxane. Most gellately is rotorbrake)distannoxane directly in the zone of the process. As the reaction medium can be used a number of different aliphatic and cycloaliphatic alcohols. It is often most economical to have carried out the reaction between the oxide di(hydrocarbon) tin (or equivalent reagent) and the alcohol or phenol by heating under reflux at atmospheric pressure. For this purpose, typically preferred are primary alcohols, lower alkyl. Thus, the preferred reaction media are the lower alkanols, such as methanol, ethanol, n-propanol, n-butanol, n-pentanol and n-hexanol. Additional alcohols and phenols that can be used as a reagent /reaction medium, are secondary alcohols such as isopropyl /rubbing alcohol and other secondary alkanols, phenol, substituted phenols, such as lower alkyl-substituted phenols, substituted cyclohexanol and cyclohexanone, such as lower alkyl-substituted cyclohexanol. In this reaction if desired, may be used an inert organic liquid such as toluene, xylene and other hydrocarbons.

Di(hydrocarbonate)-distannoxane can be represented by the following formula:

R'-O-Sn(R)2-O-Sn(R)2-O-R', in which each group R is a group hydrocarbide, for example, alkyl, cycloalkyl, aryl or aralkyl. The reaction between sucrose and di(hydrocarbonate) distannoxane is carried out at such temperature and for such a period of time sufficient for the formation of di(hydrocarbon)-standardisasi. So, for example, reaction temperatures are in the range of about 50-150aboutC. Most preferably the reaction takes place at normal temperature (i.e. at atmospheric pressure) flavobacteria reaction medium. Thus, the reaction time is about 1-24 hours

Di(hydrocarbon) standaardisatie extracted by methods similar to those already known in this field. The reaction medium is removed by distillation, which can be carried out optionally under reduced pressure. This product is solid and can be purified if desired by recrystallization.

P R I m e R 1. 1,3-Di-(6-0-Saharsa)-1,1,3,3-tetramethyldisiloxane (DBSS).

Sucrose (50 g) and the oxide dibutyrate (38,2 g) are boiled in boiling methanol (1 l) at reflux until then, until a clear solution is obtained (2.5 hours). The solution is evaporated and the residual product is dried by evaporation WacoSn2.

Found Around 41.28 C; H 6,84; Sn 20,63.

Thermogravimetric analysis (TGA) showed a weight loss of 18% when heated material to 204-218aboutC.

Differential scanning calorimetry (DSC) showed two ectothermy. The first begins at 172aboutWith a maximum peak accounted for 184aboutC (H 48 J/g); the second begins at 207aboutAnd the maximum peak falls at 212about(N 97,3 J/g). The first exothermic effect is associated, perhaps, with the collapse of the complex, while the second is due to the decomposition of carbohydrate and correlates with the observed in the TGA weight loss of 18%

Specific rotation []20+ 34o(CH3OH, C 0,31).

Spectral data.

a) Nuclear magnetic resonance (NMR)119Sn complex shows a single resonance at -183,034 million D. related to tetramethylsilane (0 million days) in DMF, which is consistent with the structure of distannoxane.

b) NMR Data13To confirm that one sucrose accounted for the remainder dibutylamine. The peaks of the resonance were assigned as follows: Sucrose: Glucosyl Fructose192,097 64,053273,917* 103,103374,121 79,379470,079 74,627573,917* 82,555661,347 60,080 (can be reversed)

< CH H2CH329,466

-CH2CH312,351 CH2CH2CH325,724

1. 1,3-Di-(6,0-Saharsa)-1,1,3,3-tetramethyldisiloxane formula

< / BR>
2. The way to obtain 1,3-di-(6,0-Saharsa)- 1,1,3,3-tetramethyldisiloxane, wherein interact oxide dibutylamine in boiling methanol with sucrose at a molar ratio of 1:1 during the time necessary to obtain a clear solution.


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