Takeda Chemical Industries, Inc.

The Kitasato Institute

Masayasu Kato

Kenzo Naito

Kazuo Tsukamura

Toru Ishida

Satoshi Omura

Susumu Tsushima

Michiyuki Sendai

Tadashi Hanaoka

Norichika Matsumoto

Miichiro Arita

Hideo Hashimoto

Shoichiro Fujii

Norio Iwano

Yoshio Toyoshima

The present invention is to provide an industrially useful production method of an aminobenzene compound represented by the formula:

Production method of aminobenzene compound

A method of producing an N-demethyl-N-isopropyl-8,9-anhydroerythromycin A-6,9-hemiacetal or a salt thereof, characterized in that an N-demethylerythromycin A or a salt thereof is reacted with an isopropylating agent and subsequently treated under acidic conditions, and a method of producing a substantially pure crystal of an 8,9-anhydroerythromycin A-6,9-hemiacetal derivative represented formula (VI): ##STR1## wherein R.sup.1 and R.sup.2, whether identical or not, represent an alkyl having 1 to 6 carbon atoms, an alkenyl having 2 to 6 carbon atoms or an alkynyl having 2 to 6 carbon atoms; R.sup.3 represents hydrogen or a hydroxyl group; one of R.sup.4 and R.sup.5 represents hydrogen and the other represents a hydroxyl group, or R.sup.4 and R.sup.5 bind together to represent O.dbd.; R.sup.6 represents hydrogen or a hydroxyl group that may be substituted for; R.sup.7 represents hydrogen or a hydroxyl group; or a salt thereof, characterized in that a crude crystal of said 8,9-anhydroerythromycin A-6,9-hemiacetal derivative or a salt thereof is recrystallized as a solvation product from hydrated isopropanol.

Method of producing erythromycin derivative

A substantially solvent-free and stable crystal of the compound of the formula: ##STR1## wherein the ring A may optionally be substituted, R.sup.1 represents hydrogen or an N-protecting group, each of R.sup.2, R.sup.3 and R.sup.4 (1) a hydrogen atom, (2) an alkyl group which may optionally be substituted with halogen atom(s) or (3) an alkoxy group which may optionally be substituted with halogen atom(s) or alkoxy; or its salt, is produced by subjecting a solvate of the compound (I) or its salt to de-solvent treatment, in an industrially advantageous method.

Crystals of benzimidazole derivatives and their production

2-(2-pyridylmethylsulfinyl)benzimidazole compounds are produced by subjecting 2-(2-pyridylmethylthio)benzimidazole compounds to oxidation with hydrogen peroxide in the presence of vanadium compounds in good yield and with low production of by-products.

Production of 2-(2-pyridylmethylsulfinyl) benzimidazole compounds by

A diphenylmethane compound (III) can be produced in a good yield by allowing a phenol compound (I) to react with a stilbene compound (II) in the presence of methanesulfonic acid ##STR1##

Process for preparing diphenylmethane compounds

Nitrogen-containing heteroaromatic compounds having an alkoxy group can be produced by reacting nitrogen-containing heteroaromatic compounds having a nitro group with alcohol or alcoholate in the presence of a phase transfer catalyst and a base.

Method of producing nitrogen-containing heteroaromatic compounds having

A novel method of producing a cephalosporin compound of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or an acyl group; R is a hydrogen atom or an ester residue; the dotted line means a double bond in 2- or 3-position of the cephem ring; and R.sup.4 is a nucleophilic compound residue, or a salt thereof, directedly in one step from a compound of the formula ##STR2## wherein R.sup.1, R and the dotted line have the meanings defined above, or a salt thereof, by reacting in the presence of an organic solvent the compound [II] or a salt thereof, a nucleophilic compound or a salt thereof, and (1) a trivalent or pentavalent cyclic phosphorus compound having a partial structure of the formula ##STR3## wherein W is an oxygen atom, a sulfur atom or NR.sup.2 ; W.sup.1 is an oxygen atom, a sulfur atom or NR.sup.3 ; and R.sup.2 and R.sup.3 may be the same or different and each means a hydrogen atom or a hydrocarbon group, or a salt thereof, or (2) a reaction product of a compound having a partial structure of the formula ##STR4## wherein W and W.sup.1 have the same meaning as defined above, or a salt thereof, with a phosphorus oxyhalide, trihalide or pentahalide.

Method for production of cephalosporin compounds

A method is provided for producing a 1,3,2-dioxaphosphole of the formula ##STR1## wherein ##STR2## respresents a benzene ring which may be substituted and R represents an aryl, alkoxy or aralkyloxy group which may be substituted, which comprises reacting a catechol compound of the formula ##STR3## wherein ##STR4## is an defined above, with a compound of the formula ##STR5## wherein X is a halogen atom and R is as defined above, at a temperature not higher than about 30.degree. C. in the presence of a base.

Method for production of 1,3,2-dioxaphospholes

7-Aminocephalosporin of the formula: ##STR1## wherein R.sup.2 is 3-oxobutyryloxy group, 1-methyl-1H-tetrazol-5-ylthio group or 1-(2-dimethylaminoethyl)-1H-tetrazol-5-ylthio group, or its salt is prepared by first protecting the carboxyl group at 4-position of the compound of the formula: ##STR2## wherein R.sup.1 is an amino group which may be protected and R.sup.2 is the same as defined above, or its salt with an acetyl or propionyl halide, then cleaving the amide group at 7-position of said compound by converting the amide bond to an imino halide, then to an imino ether and subjecting the imino ether to solvolysis.

Process for preparing 7-aminocephalosporins

Penicillin-1-oxides are rearranged into the corresponding 3-desacetosycephalosporin derivatives in an inert organic solvent in the concomitant presence of an acid catalyst and an organic sulfide in a good yield and with a high purity.

Growing community of inventors

Hyogo, Japan

Masayasu Kato