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GB1586677A - Manufacture of n-(3,4-dimethylphenyl)-d-ribamine - Google Patents

Manufacture of n-(3,4-dimethylphenyl)-d-ribamine Download PDF

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Publication number
GB1586677A
GB1586677A GB45920/77A GB4592077A GB1586677A GB 1586677 A GB1586677 A GB 1586677A GB 45920/77 A GB45920/77 A GB 45920/77A GB 4592077 A GB4592077 A GB 4592077A GB 1586677 A GB1586677 A GB 1586677A
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United Kingdom
Prior art keywords
ribamine
dimethylphenyl
lactone
dimethylnitrobenzene
partially reduced
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Expired
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GB45920/77A
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BASF SE
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BASF SE
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/52Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

N-[3,4-dimethylphenyl]-D-ribamine of the formula I is prepared in pure form and with a good yield by the catalytic hydrogenation of D-ribono- gamma -lactone. The reaction is carried out in the presence of an organic solvent and a 3,4-dimethylbenzene derivative whose nitro group is partially reduced. The symbols of the formula I have the meaning given in Patent Claim 1. <IMAGE>

Description

(54) MANUFACTURE OF N-[3,4-DIMETHYLPHENYL]-D-RIBAMINE (71) We, BASF AKTIENGESELLSCHAFT, a German Joint Stock Company of 6700 Ludwigshafen, Federal Republic of Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: The present invention relates to a new process for the manufacture of N-[3,4dimethylphenyl]-D-ribamine of the formula I
N-[3,4-Dimethylphenyll-D-ribamine, an important intermediate for the manufacture of vitamin B 2 can be manufactured, for example, in accordance with a process disclosed in U.S. Patent 2,384,105, by reacting D-ribose and 3,4-dimethylaniline, followed by catalytic hydrogenation at up to 100"C. Since, as is known, D-ribose is difficult to obtain, U.S.
Patent 2,411,611 discloses a process wherein 3,4-dimethylaniline is condensed with D-ribonic acid y-lactone to give D-ribonic acid 3,4-dimethylanilide. N-[3,4 Dimethylphenyl]-D-ribamine is then manufactured from the anilide by acetylation, chlorination, hydrogenation and deacetylation. N-[3,4-Dimethylphenyl]-D-ribamine cannot be manufactured economically by this involved process.
It has also already been proposed to hydrogenate a mixture of 3,4-dimethylaniline, or the corresponding nitro compound. with D-ribonic acid y-lactone in an inert solvent, using platinum oxide. This process, which is disclosed in U.S. Patent 2,422,997 and which is carried out at below 1()() C to avoid side-reactions, gives moderate yields of N-[3,4 dimethylphenyl]-D-ribamine.
The earlier German Laid-Open Application DOS 2,558,515, which does not constitute a prior disclosure, describes a process in which N-[3,4-dimethylphenyl]-D-ribamine is obtained by catalytic hydrogenation of a mixture of 3,4-dimethylaniline and/or 3,4-dimethyl-nitrobenzene and D-ribonic acid, its esters or D-ribonic acid y-lactone at from 100 to 155"C. If 3,4-dimethylnitrobenzene is used as the starting material for this process, the yields are unsatisfactory. If 3.4-dimethylaniline is used, side-reactions cannot be excluded. Thus. 3,4-dimethylaniline may react with D-ribonic acid y-lactone to give D-ribonic acid 3,4-dimethylanilide (J.Chem.Soc.1945,167). Furthermore, at about 1300C 3,4-dimethylaniline catalyzes the epimerization of D-ribonic acid y-lactone to D-arabonic acid y-lactone, which in the presence of 3,4-dimethylaniline undergoes hydrogenation to give the undesired product N-[3.4-dimethylphenyl]-D-arabinamine.
We have found that N-(3q4-dimethylphenyl)-D-ribamine of the formula I
can be manufactured particularly advantageously by a method wherein D-ribonic acid y-lactone is catalytically hydrogenated in an organic solvent and in the presence of a 3,4-dimethylnitrobenzene derivative in which the nitro group is partially reduced.
Examples of 3,4-dimethylnitrobenzene derivatives in which the nitro group is partially reduced are derivatives of 3,4-dimethyl-benzene which contain an azoxy, azo, hydrazo, nitroso, hydroxylamino or diazoamino group in the 1-position, i.e. the compounds of the general formula II
where X is one of the radicals -NO, -NHOH, -NH-N=N-R, -NH-NH-R, -N=N-R and -NO=N-R, and R is 3,4-dimethylphenyl.
The following compounds are examples,of starting materials of the general formula II: 3,4,3' ,4'-tetramethylazoxybenzene, 3,4,3' ,4'-tetramethylazobenzene, 3,4,3' 4'- tetramethylhydrazobenzene, 3,4-dimethylnitrosobenzene, 3,4,3',4'- tetramethyldiazoaminobenzene and 4-hydroxylamino-o-xylene. Of these compounds, 3,4,3',4'-tetramethylazoxybenzene and 3,4,3' ,4'-tetramethylazobenzene are preferred.
Suitable solvents are conventional organic solvents which undergo little or no change under the catalytic hydrogenation conditions. Examples are alcohols, eg. methanol, ethanol, propanol and butanol, or ethers, eg. dioxane, the latter being the preferred solvent.
Examples of catalysts which may be used for the catalytic hydrogenation are metals from amongst the transition elements, eg. copper, chromium, nickel, iron, platinum, palladium, rhodium, cerium, thorium and zinc, the metals aluminum and magnesium and the oxides of the said metals. Mixtures of the said metals or.metal oxides, for example the mixed oxides described in Schwab: "Handbuch der Katalyse", Volume 5, pages 567-577, are also very suitable. Copper oxide and/or copper-containing catalysts, especially those which contain finely divided copper oxide and/or copper on a catalyst carrier, have proved particularly advantageous. Examples of carriers present in these catalysts are refractory oxides, e.g.
chromium oxide, aluminum oxide or cerium oxide. Such catalysts are described, for example, by H. Adkins in Organic Reactions, Volume VIII, 1954, pages 8 and 9 and in German Laid-Open Application DOS 2,024,282. Amongst these catalysts, those containing copper oxide and chromium oxide and those containing copper oxide and aluminum oxide are very suitable.
It is particularly advantageous to treat the catalysts with hydrogen before they are used.
This prehydrogenation is carried out at. for example, up to 400"C, preferably at from 150 to 2500C and under a hydrogen pressure of from 0.01 bar (in the absence of a solvent) to 300 bars (in the case of a suspension in a solvent).
The hydrogenation according to the invention is preferably carried out at from 70 to 160"C, above all at from 125 to 145 C. The hydrogen pressure is advantageously from 1 to 1,000, preferably from 100 to 300 bars. Advantageously, the starting materials are reacted in the stoichiometric ratio. Advantageously, from 100 to 400 parts by weight of solvent are used per 100 parts by weight of the mixture of the starting materials.
The process of the invention is able to give pure N-[3,4-dimethylphenyll-D-ribamine in good yield. N-[3.4-dimethylphenyll-D-ribamine thus obtained may be converted into vitamin B 2 by the methods described in J. Fragner: Vitamine, Volume II, G. Fischer Verlag, Jena, page 1381.
Example 1 Hydrogenation of 3,4,3',4'-tetramethyl-azoxy-benzene with D-ribonic acid y-lactone to give N-[3,4-dimethylphenyl]-D-ribamine
18 g of a copper oxide/aluminum oxide catalyst are pre-hydrogenated in 150 ml of dioxane for 8 hours at 2000C under 150 bars hydrogen pressure. 12.7 g (0.05 mole) of 3,4,3',4'-tetramethyl-azoxy-benzene and 14.8 g (0.1 mole) of D-ribonic acid y-lactone are then added and the mixture is hydrogenated for 24 hours at 135"C and 250 bars hydrogen pressure. After completion of the hydrogenation, and after cooling, 125 ml of ethanol are added and the mixture is heated in order to dissolve the partially precipitated N-[3,4-dimethylphenylj-D-ribamine. The catalyst is filtered off, the filtrate is concentrated and the residue is recrystallized from ethanol.
Yield: 70% of N-[3,4-dimethylphenyl]-D-ribamine [a]D = -23.54" (C = 0.4; methanol) Analysis C13H21NO4, molecular weight: 255.31 %C %H %O %N calculated: 61.1 .8.1 25.1 5.9 found: 61.15 8.29 25.07 5.49 l3C-NMR spectrum (DDMSO; TMS-standard): chemical shift (ppm): 147.2; 136.0; 129.8; 122.8; 114.1; 109.9; 73.5; 72.8; 70.3; 63.2; 46.0; 19.7; 18.3.
Example 2 Hydrogenation of 3,4,3' ,4'-tetramethylhydrazobenzene with D-ribonic acid y-lactone to give N-[3 ,4-dimethylphenyl]-D-ribamine
24.03 g (0.1 mole) of 3,4,3'*4'-tetramethylhydrazobenzene and 29.6 g (0.2 mole) of D-ribonic acid y-lactone are hydrogenated with 18 g of a copper oxide/aluminum oxide catalyst, which has been prehydrogenated as described in Example 1, for 24 hours at 1350C and 290 bars hydrogen pressure. The mixture is worked up as described in Example 1.
Yield: 75% of N-[3,4-dimthylphenyl]-D-ribamine Example 3 Hydrogenation of 3,4,3' ,4'-tetramethylazobenzene with D-ribonic acid y-lactone to give N-[3.4-dimethylphenyl]-D-ribamine
29.6 g (0.2 mole) of D-ribonic acid y-lactone and 23.8 g (0.1 mole) of 3,4,3',4'tetramethylazobenzene are hydrogenated with 18 g of a copper oxide catalyst (which has been prehydrogenated for 8 hours at 200"C in dioxane), for 24 hours at 135"C under 300 bars hydrogen pressure. After completion of the hydrogenation, 300 ml of ethanol are added, the mixture is heated, the catalyst is filtered off and the filtrate is concentrated, The residue is recrystallized from 150 ml of ethanol.
Yield: 60% of N-[3,4-dimethylphenyl]-D-ribamine.
The IR spectrum and '3C-NMR spectrum agree with the structure of N-[3,4 dim ethylphenyl]-D-ribamine.
Analysis: Cl3H2,NO4 %C %H %O %N calculated: 61.1 8.1 25.3 5.3 found: 61.15 8.29 25.07 5 49 WHAT WE CLAIM IS: 1. A process for the manufacture of N-[3,4-dimethylphenyl]-D-ribamine of the formula
in which D-ribonic acid y-lactone is catalytically hydrogenated in an organic solvent and in the presence of a 3,4-dimethylnitrobenzene derivative in which the nitro group is partially reduced.
2. A process as claimed in claim 1, in which the partially reduced derivative of 3,4-dimethylnitrobenzene is a 3,4-dimethylbenzene which has an azoxy, azo, hydrazo, nitroso, hydroxylamino or diazoamine group in the 1-position.
3. A process as claimed in claim 1, in which 3,4,3',4'-tetramethylazoxybenzene or 3,4,3',4'-tetramethylazobenzene is used as the partially reduced 3,4-dimethylnitrobenzene derivative.
4. A process as claimed in any of claims 1 to 3, in which the hydrogenation is carried out with a catalyst which contains copper oxide and/or copper.
5. A process for the manufacture of N-[3,4-dimethylphenyl]-D-ribamine carried out substantially as described in any of the foregoing Examples.
6. N-[3,4-dimethylphenyl]-D-ribamine when manufactured by a process as claimed in any of claims 1 to 5.
7 Vitamin B 2 when obtained from N-[3 ,4-dimethylphenyl]-D-ribamine manufactured by a process as claimed in any of claims 1 to 5.
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (6)

**WARNING** start of CLMS field may overlap end of DESC **. 29.6 g (0.2 mole) of D-ribonic acid y-lactone and 23.8 g (0.1 mole) of 3,4,3',4'tetramethylazobenzene are hydrogenated with 18 g of a copper oxide catalyst (which has been prehydrogenated for 8 hours at 200"C in dioxane), for 24 hours at 135"C under 300 bars hydrogen pressure. After completion of the hydrogenation, 300 ml of ethanol are added, the mixture is heated, the catalyst is filtered off and the filtrate is concentrated, The residue is recrystallized from 150 ml of ethanol. Yield: 60% of N-[3,4-dimethylphenyl]-D-ribamine. The IR spectrum and '3C-NMR spectrum agree with the structure of N-[3,4 dim ethylphenyl]-D-ribamine. Analysis: Cl3H2,NO4 %C %H %O %N calculated: 61.1 8.1 25.3 5.3 found: 61.15 8.29 25.07 5 49 WHAT WE CLAIM IS:
1. A process for the manufacture of N-[3,4-dimethylphenyl]-D-ribamine of the formula
in which D-ribonic acid y-lactone is catalytically hydrogenated in an organic solvent and in the presence of a 3,4-dimethylnitrobenzene derivative in which the nitro group is partially reduced.
2. A process as claimed in claim 1, in which the partially reduced derivative of 3,4-dimethylnitrobenzene is a 3,4-dimethylbenzene which has an azoxy, azo, hydrazo, nitroso, hydroxylamino or diazoamine group in the 1-position.
3. A process as claimed in claim 1, in which 3,4,3',4'-tetramethylazoxybenzene or 3,4,3',4'-tetramethylazobenzene is used as the partially reduced 3,4-dimethylnitrobenzene derivative.
4. A process as claimed in any of claims 1 to 3, in which the hydrogenation is carried out with a catalyst which contains copper oxide and/or copper.
5. A process for the manufacture of N-[3,4-dimethylphenyl]-D-ribamine carried out substantially as described in any of the foregoing Examples.
6. N-[3,4-dimethylphenyl]-D-ribamine when manufactured by a process as claimed in any of claims 1 to 5.
7 Vitamin B 2 when obtained from N-[3 ,4-dimethylphenyl]-D-ribamine manufactured by a process as claimed in any of claims 1 to 5.
GB45920/77A 1976-11-06 1977-11-04 Manufacture of n-(3,4-dimethylphenyl)-d-ribamine Expired GB1586677A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19762650830 DE2650830A1 (en) 1976-11-06 1976-11-06 METHOD OF MANUFACTURING ANGULAR CLAMP ON 3,4-DIMETHYLPHENYL ANGLE CLAMP TO -D-RIBAMINE

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GB1586677A true GB1586677A (en) 1981-03-25

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JP (1) JPS5359632A (en)
CA (1) CA1101887A (en)
CH (1) CH630602A5 (en)
DE (1) DE2650830A1 (en)
FR (1) FR2370033A1 (en)
GB (1) GB1586677A (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL60827C (en) * 1944-12-15
NL7614211A (en) * 1975-12-24 1977-06-28 Basf Ag PROCESS FOR THE PREPARATION OF N- (3,4-DIMETHYL-PHENYL) -D-RIBAMINE.
DE2558515C3 (en) * 1975-12-24 1979-02-01 Basf Ag, 6700 Ludwigshafen Process for the preparation of N- [3,4-dimethylphenyl] D-ribamine

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CH630602A5 (en) 1982-06-30
JPS5359632A (en) 1978-05-29
FR2370033A1 (en) 1978-06-02
DE2650830A1 (en) 1978-05-11
CA1101887A (en) 1981-05-26
FR2370033B1 (en) 1981-12-18

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