Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-04-07
2003-10-21
Stockton, Laura L. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06635770
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing hexahydrothieno[3,4-d]imidazole-2,4-diones. More particularly, the present invention concerns a process for producing hexahydrothieno[3,4-d]imidazole-2,4-diones which are useful as an intermediate for the preparation of biotin (vitamin H).
2. Description of Related Art
Heretofore, as a method for producing hexahydrothieno[3,4-d]imidazole-2,4-diones using hexahydrofuro[3,4-d]imidazole-2,4-diones as a raw material, the following methods have been known.
1. A method in which hexahydrofuro[3,4-d]imidazole-2,4-dione is reacted with an alkali metal salt of thioacetic acid as disclosed in Helvetica Chimica Acta, 53, 991-999 (1970), and
2. a method in which hexahydrofuro[3,4-d]imidazole-2,4-dione is reacted with thioamides as disclosed in Japanese examined patent publication Shou 62-7196.
However, the first method required stoichiometric amount of unstable and expensive alkali metal salt of thioacetic acid, and the second method is not always satisfactory in yield.
SUMMARY OF THE INVENTION
An object of the present invention is to provide an industrially advantageous process for producing hexahydrothieno[3,4-d]imidazole-2,4-diones of the following formula (1).
The present inventors have intensively studied to solve the above problem. As a result, they have found an industrially advantageous process for producing hexahydrothieno[3,4-d]imidazole-2,4-diones which are important as the intermediate of biotin, and they have accomplished the present invention.
The present invention provides:
1. A process for producing hexahydrothieno[3,4-d]imidazole-2,4-diones of formula (1):
wherein R
1
and R
2
are the same or different and independently represent
a hydrogen atom, an alkyl, alkenyl, aryl or aralkyl group all of which may be substituted, which comprises:
reacting hexahydrofuro[3,4-d]imidazole-2,4-diones of formula (2):
wherein R
1
and R
2
are the same as defined above with thioamide in the presence of alkali hydrogen sulfide, sulfur and a basic compound selected from alkali metal carbonate, alkali metal sulfide, an alkali metal salt of the carboxylic acid having C2-C6 carbon atoms and an organic base having C6-C10 carbon atoms.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
First, a description will be made to a process for producing hexahydrothieno[3,4-d]imidazole-2,4-diones of the formula (1) as defined above, which comprises: reacting hexahydrofuro[3,4-d]imidazole-2,4-diones of formula (2) as defined above with thioamide in the presence of alkali hydrogen sulfide, sulfur and a basic compound selected from alkali metal carbonate, alkali metal sulfide, an alkali metal salt of the carboxylic acid having (C2-C6) carbon atoms and an organic base having C6-C10 carbon atoms.
The compound of formula (2) may be an optical isomer, a mixture thereof, or a racemate, which can be optionally selected.
In hexahydrofuro[3,4-d]imidazole-2,4-diones of formula (2) and hexahydrothieno[3,4-d]imidazole-2,4-diones of formula (1), R
1
and R
2
are the same or different and independently represent a hydrogen atom, an alkyl, alkenyl, aryl or aralkyl group all of which may be substituted. Compounds of formula (2) wherein R
1
and R
2
are the same are preferably used.
Examples of the alkyl group which may be substituted include, for example, a straight or branched chain (C1-C8) alkyl group such as a methyl group, an ethyl group, n-propyl group, an i-propyl group, an n-butyl group, a t-butyl group, an n-hexyl group, and an n-octyl group and the alkyl group may be substituted with at least one group selected from a halogen atom (e.g., a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom), an (C1-C3) alkoxy group (e.g., a methoxy group, an ethoxy group, and an i-propxy group). Specific examples of the alkyl group include a haloalkyl group such as a fluoromethyl group, chloromethyl group or a chloroethyl group, and an alkoxyalkyl such as a methoxymethyl group. Among these groups, (C1-C4) alkyl groups are preferably used.
Examples of the alkenyl group which may be substituted include a straight or branched chain (C2-C8) alkenyl group such as a vinyl group, an allyl group, 2-butenyl group or a 3-methyl-2-butenyl group. Said alkenyl group may be substituted with at least one group selected from a halogen atom and an alkoxy group as described above for the alkyl group. Specific examples thereof include a haloalkenyl group and an alkoxyalkenyl group.
Among the alkenyl groups, preferred are (C3-C4)alkenyl groups.
The aryl and aralkyl group may be substituted on the aryl groups with at least one group selected from an (C1-C3)alkyl group, an (C1-C3)alkoxy group, a nitro group and a halogen atom (e.g., fluorine, chlorine, bromine, iodine).
Examples of the aryl group which may be substituted include a phenyl group, a naphthyl group, a chlorophenyl group, a methoxyphenyl group, a nitrophenyl group a xylyl group, a tolyl group and 1-methylnaphthyl group and 2-methylnaphthyl group. The phenyl, tolyl and naphthyl groups are preferred.
Examples of the aralkyl group which may be substituted include an aryl-substituted (C1-C3)alkyl group such as a benzyl group, a phenylethyl group, a naphthylmethyl group, a methoxybenzyl group, a bromobenzyl group, a nitrobenzyl group, and a methylbenzyl group.
Among them, the benzyl group, methoxybenzyl group are preferred and particularly the benzyl group is preferred.
Specific examples of the compound of formula (2) include:
hexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-dimethylhxahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-diethylhexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-di(n-propyl)hexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-diallylhexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-di(2-butenyl)hexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-di(2-methyl-3-butenyl)hexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-diphenylhexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-ditolylhexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-diphenylhexahydrofuro[3,4-d]imidazole-2,4-dione,
1,3-di(methoxybenzyl)hexahydrofuro[3,4-d]imidazole-2,4-dione and
1,3-di(bromobenzyl)hexahydrofuro[3,4-d]imidazole-2,4-dione.
1,3-diallylhexahydrofuro[3,4-d]imidazole-2,4-dione, 1,3-dibenzylhexahydrofuro[3,4-d]imidazole-2,4-dione and 1,3-di(methoxybenzyl)hexahydrofuro[3,4-d]imidazole-2,4-dione are preferred.
Examples of the thioamide to be reacted with the compound of formula (2) include, for example, a (C2-C4) aliphatic thioamide such as thioacetamide or thiopropionamide,
a C6 aromatic thioamide which may be substituted with at least one group selected from a halogen atom, a nitro group, an amino group, a hydroxy group, and a (C1-C3) alkoxy group. Specific examples thereof include thiobenzamide, thiochlorobenzamide, thiobromobenzamide, thionitrobenzamide, thioaminobenzamide, thiomethoxybenzamide and thiohydroxybenzamide.
Preferred is the aliphatic thioamide, and thioacetamide is preferably used because of its good availability.
Examples of the alkali hydrogen sulfide include, for example, an alkali metal hydrogen sulfide such as sodium hydrogen sulfide or potassium hydrogen sulfide, and an alkaline earth metal hydrogen sulfide such as calcium hydrogen sulfide. Preferred is the alkali metal hydrogen sulfide, particularly preferred is sodium hydrogen sulfide. Said alkali hydrogen sulfide may be either anhydrous or hydrated. Said hydrated compound is usually used and the shape of the compound is not particularly limited.
Any types of sulfur (e.g. powder or lump) may be used. Preferred is powder sulfur.
The amount of the thioamide is usually 0.01 mole or more, preferably 0.05 mole or more, more preferably 0.1 mole or more per mole of the compound of formula (2).
The amount of the alkali hydrogen sulfide is usually 0.1 mole or more per mole
Miyamoto Yasunobu
Shirahata Mamoru
Uemura Toshitsugi
Stockton Laura L.
Sumitomo Chemical Company Limited
LandOfFree
Process for producing hexahydrothieno... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for producing hexahydrothieno..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing hexahydrothieno... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3126621