JPS59196855A - Biguanide derivative - Google Patents

Abstract

NEW MATERIAL:A compound of formula I (R1, R2 are H, halogen). EXAMPLE:1-( 2-Acryloylethyl )phenyl-5-p-chlorophenylbiguanide hydrochloride. USE:It has excellent antimicrobial activity, thus being suitable for use as medicines as well as bactericide or antiseptic for industrial water, fiber finishing oil, coating and other applications. It shows good properties not only in industrial fields but also in environmental hygiene. PREPARATION:The reaction of 4-(2-hydroxyethyl)phenyldicyandiamide of formula IIwith a compound of the formula: CH2=CHOX (X is halogen) forms 4-(2-acryloylethyl)phenyldicyandiamide of formula III, then the product is allowed to react with an aniline derivative of formula IV in a solvent such as ethanol in the presence of a polymerization inhibitor such as hydroquinone at 60-130 deg.C for 5-30min. After the reaction, the precipitate is filtered to give the compound of formula I .

Description

[Detailed description of the invention] The present invention relates to novel biguanide derivatives.

The uses of antimicrobial agents such as antibacterial agents, antibacterial agents, bactericidal agents, and antifungal agents are expanding year by year, and they are used not only in medicine but also in various fields such as the food industry, machinery industry, paper industry, textile industry, and environmental hygiene management. Various performances are required. Generally required performance is high antimicrobial activity and broad spectrum of action, but also blue-free for humans and animals,
Secondary performances such as odorlessness, storage stability, and ease of handling are factors that determine practical value. Although a wide variety of drugs have been developed to date, it is extremely difficult to satisfy all of these requirements at the same time (see "Chemistry of Sterilization and Mildew Prevention" by Hiroshi Hori, published in 1982). The present inventors conducted intensive research in search of a compound with excellent properties both industrially and in terms of environmental hygiene, and as a result, synthesized a new vinyl compound with a biguanide residue and discovered that this has promising properties. Ta.

The present invention is a biguanide derivative represented by the general formula (2, in which R1 and R2 represent a hydrogen atom or a halogen atom).

As the halogen atom for R1 and R2, a chlorine atom is particularly preferred.

The compound of the present invention has antibacterial activity by itself, but
The polymer compound obtained by polymerizing this also has satisfactory properties as an antibacterial agent.

The compound of formula I is a new substance that has not been described in any literature, and is a compound of 4-(2-hydroxyethyl)phenyldicyandiamide represented by the following formula, % formula % (1) (wherein X does not represent a halogen atom). ) to react the produced 4-(2-acryloylethyl)phenyldicyandiamide represented by the following formula with an aniline derivative represented by the formula -4 (wherein R1 and R2 have the above-mentioned meanings). Obtained by reaction.

Compounds of formula (1) and Ill are also new substances, and the compound of formula (1) is obtained by reacting p-aminophenethyl alcohol hydrochloride with sodium siphanimide in the presence of a solvent.

Examples of solvents used include water, dioxane, and tetrahydrofuran. The reaction temperature is 6° to 100°C, preferably 80 to 95°C, and the reaction is completed in 1 to 6 hours. After the reaction is complete, the reaction mixture is cooled and the compound of formula II precipitates out.

The halogen atom for the substituent X in the compound of formula (1) is preferably a chlorine atom. Moreover, it is preferable to use the compound of 2V as an acid addition salt.

The acid that forms the acid addition salt of the compound of formula ■ is:
Examples include hydrochloric acid and nitric acid.

The reaction of the compounds of formula (1) and I is preferably carried out in the presence of a solvent. Examples of solvents include water, tetrahydrofuran,
Dioxane etc. and mixtures thereof are used. The reaction temperature is 0 to 40°C, preferably 15 to 25°C, and when the precipitate is collected after the reaction is completed, the compound of formula (2) is obtained.

The reaction between the compounds of formulas 1 and 2 is preferably carried out in the presence of a solvent and a polymerization inhibitor. As the solvent, for example, ethanol, ingropanol, butanol, ethylethanol, etc. are used, and as the polymerization inhibitor, for example, hydroquinone, catechol, etc. are used.

The reaction temperature is 60 to 130'C, preferably the boiling temperature of the reaction mixture. The reaction is completed in 5-6 minutes. After the reaction is complete,
When the deposited precipitate is collected, the compound of formula (1) or its acid addition salt is obtained.

The compounds of formula I have excellent antimicrobial activity and are useful as medicines and as disinfectants and preservatives for industrial water, textile oils, metal working oils, paints, etc.

The antibacterial spectrum of the compound of formula I against various microorganisms is shown in the table below. The values in the table indicate the minimum inhibitory concentration (ppm) determined by the agar dilution method. In addition, the symbol Bs in the table is Bacillus subtilis, Ec is Nijierisia coli, and Aa
indicates Aerobacter-Aerobacter, Pa indicates Pseudomonas aeruginosa, and Mp indicates Micrococcus pyogenes perle aureus. The antibacterial activity test was conducted using a bouillon agar medium and cultured at 67°C for 48 hours.

Synthesis example of compound of formula (■)-Aminophenethyl alcohol 51.9 (0゜6
After dissolving 7 mol) in 550 ml of dioxane and passing hydrogen chloride gas through it at room temperature for 60 minutes, the precipitate was isolated, p-aminophenethyl alcohol hydrochloride 5
09 is obtained. This p-aminophenethyl alcohol hydrochloride 17.4. ! 9 (0.1 mol) and sodium dicyanimide 90.9 (0.1 mol) in 200 m of water.
4-(2
-Hydroxyethyl)phenyldicyandiamide16.
819 (yield 68%, melting point 172-174
”C).

NMi' ((DMSOdo, δ) 2.70 (2H, t, -CH2-) 3.67 (2H1t, -CH20H-) 6.92 (
2H,s, proton of dicyandiamide group) Z25 (
4H, s, proton of aromatic nucleus) 9.02 (proton of IH1S1 dicyandiamide group) Elemental analysis value C, HN Calculated value: 58.80 5.92 27.44 Actual value: 58.78 5.98 27.45 Formula Synthesis Example of Compound IV 15.0 g (0,074 mol) of -(2-hydroxyethyl)phenyldicyandiamide was dissolved in a mixed solvent of 82 ml of tetrahydrofuran and 9 me of water, and 48 mg of acrylic acid chloride was added dropwise in a water bath. The precipitate deposited after being left at room temperature overnight is collected to obtain 4-(2-acryloylethyl)phenyldicyandiamide 1Zag (yield 94%, melting point 157-159°C).

N1vH ((DMSO-d6, δ) 2.90 (2H, t, -c 曵-) 4.30 (2H, t, , -C ○-) 5.9 to 6.4
(3H, m, proton of vinyl/l/ group) 6.95 (
2H,s, proton of dicyandiamide group) 7.30 (
4H,s, proton of aromatic nucleus) 9.05 (IH,s, proton of dicyandiamide group) Example 1 4-(2-7 chloroylethyl)phenyldicyandiamide 8.7.9 (0,034 mol) and p-/ /o
/L/ 7 = IJ-HCl tm5.5 g ((1,0
54 mol) in Ingropil Alcohol #60ml
Heat at reflux for 0 minutes. After cooling, the deposited precipitate was collected, and 1-(2-acryloylethyl)phenylene, /l/-
5-'-Ll //lorphenylhycuanito hydrochloride +y
, <9.7 g are obtained (yield 69%, melting point 204
~206°C, decomposition).

Group love (Cr]3or+) 4, 33 (2+1, t, -cr(2-oco-)
4.77 (6H5E, biguanide group proton) 5
．． 8-6.4 (3H1S, vinyl group o-l-n)
7.30 (4H1J1, aromatic nucleus proton) 7.35 (
41-L s, proton of aromatic nucleus) Example 2 4-(2-acryloylethyl)phenyldicyandiamide 3.0.9 (0,0
12 moles) and aniline hydrochloride 1°6.9 (0,012
mol) in 10 ml of impropanol in the presence of a small amount of polymerization inhibitor (hydroquinone) for 15 minutes under reflux. After cooling, the number of precipitates deposited is 1-(2-
Acryloylethyl) phenyl-5-phenyl biguanide 2, 3,! 9 (yield 49%, melting point 182
~185°C1 decomposition).

NMR (CD, OD) 2.90 (2H, t, -CH2-) 4,50 (2H, t, -cry2-o -) 4.7
7 (6H,s, proton of biguanide group) 5.8-6
．． 4 (3H, m, vinyl group proton) 7.20 (5
H, s, proton of aromatic nucleus) 7.25 (4H, s, proton of aromatic nucleus) Example 6 4-(2-acryloylethyl)phenyldicyandiamide 3, Og(o ,01
2 mol) and 6,4-dichloroaniline hydrochloride 2.3.
! 9 (0,012 mol), Impropatool 10me
When treated in the same manner as in Example 2, 2.4 g of 1-(2-acryloylethyl)phenyl-5-(3,4-si/lorphenyl)hyphanide hydrochloride is obtained (yield 45%).
, melting point 186-189°C, decomposition).

1R(CD30D) 2,95 (2H,,t, -cI(2-)4,65
(2H, t, -c■〕2-〇=)4.80 (6HSs
, proton of biguanide group) 5.8 to 6.4 (3I-
L m, vinyl group proton) 71-7.7 (7H,
m, proton of aromatic nucleus) Agent: Masao Kobayashi, patent attorney

Claims (1)

[Scope of Claims] A biguanide derivative represented by the general formula (wherein R3 and R2 represent a hydrogen atom or/and a rogen atom).