Biocidal benzylbiphenyl derivatives

• US 6,440,440 B1
• Filed: 09/22/2000
• Issued: 08/27/2002
• Est. Priority Date: 04/02/1998
• Status: Expired due to Fees

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Van der Flaas, Mark Arthur Josepha, Heeres, Jan, Meerpoel, Lieven, Van Der Veken, Louis Jozef Elisabeth
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US09/647,015
• Time in Patent Office: 704 Days
• Field of Search: 424/405, 546/191, 546/223, 546/229, 546/316, 504/248, 504/326
• US Class Current: 424/405
• CPC Class Codes: A01N 33/04 Nitrogen directly attached to aliphatic or cycloaliphatic carbon atoms
• CPC Class Codes: A01N 33/12 Quaternary ammonium compounds
• CPC Class Codes: A01N 43/40 six-membered rings
• CPC Class Codes: C07C 211/27 having amino groups linked to the six-membered aromatic ring by saturated carbon chains
• CPC Class Codes: C07C 211/28 having amino groups linked to the six-membered aromatic ring by unsaturated carbon chains
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 211/70 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Abstract

This invention concerns compounds of formula.

stereochemically isomeric forms thereof, acid or base addition salts thereof, N-oxides thereof, or quaternary ammonium derivatives thereof, wherein the dotted line is an optional bond; X is a direct bond when the dotted line represents a bond, or X is hydrogen or hydroxy, when the dotted line does not represent a bond; R¹, R², R⁵ and R⁶ are each independently selected from hydrogen, halo, hydroxy, C_1-4alkyl, C_1-4alkyloxy, —SO₃H, and the like; R³ and R⁴ are each independently selected from hydrogen, halo, hydroxy, C_1-4alkyl, C_1-4alkyloxy, nitro, amino, cyano, trifluoromethyl, or trifluoromethoxy; L is a radical of formula

wherein A¹ is a direct bond or C_1-6alkanediyl; A² is C_2-6alkanediyl; and R⁷ to R¹¹ are hydrogen, C_1-6alkyl, aminoC_1-6alkyl and the like; having biocidal properties; their preparation, compositions containing them and their use as a biocide.

Claims

1. A compound of formula (I)

a stereochemically isomeric form thereof, an acid or base addition salt thereof, an N-oxide thereof, or a quaternary ammonium derivative thereof,

wherein

the dotted line is an optional bond;

X is a direct bond when the dotted line represents a bond, or

X is hydrogen or hydroxy, when the dotted line does not represent a bond;

R¹ and R² are each independently selected from hydrogen, halo, hydroxy, C_1-4alkyl, C_1-4alkyloxy, nitro, amino, cyano, trifluoromethyl, trifluoromethoxy, C_1-6alkylcarbonyl hydroxycarbonyl, C_1-6alkyloxycarbonyl, aminocarbonyl, di(C_1-4alkyl)aminocarbonyl, C_1-6alkylsulfinyl, C_1-6alkylsulfonyl, aminosulfonyl, di(C_1-4alkyl)aminosulfonyl, or —

SO₃H;

R³ and R⁴ are each independently selected from hydrogen, halo, hydroxy, C_1-4alkyl, C_1-4alkyloxy, nitro, amino, cyano, trifluoromethyl, or trifluoromethoxy;

R⁵ and R⁶ are each independently selected from hydrogen, halo, hydroxy, C_1-4alkyl, C_1-4alkyloxy, nitro, amino, cyano, trifluoromethyl, trifluoromethoxy, C_1-6alkylcarbonyl, hydroxycarbonyl, C_1-6alkyloxycarbonyl, aminocarbonyl, di(C_1-4alkyl)aminocarbonyl, C_1-6alkylsulfinyl, C_1-6alkylsulfonyl, aminosulfonyl, di(C_1-4alkyl)aminosulfonyl, or —

SO₃H,

L is a radical of formula

 

wherein

A¹ is a direct bond or C_1-6alkanediyl;

A² is C_2-6alkanediyl;

R⁷ is hydrogen, C_1-4alkyl, phenyl or benzyl;

R⁸ and R⁹ are each independently hydrogen, C_1-6alkyl, aminoC_1-6alkyl or mono- or di(C_1-4alkyl)aminoC_1-6alkyl;

R¹⁰ is hydrogen, C_1-6alkyl, aminoC_1-6alkyl or mono- or di(C_1-4alkyl)aminoC_1-6alkyl; and

R¹¹ is hydrogen, C_1-6alkyl, amino, aminoC_1-6alkyl or mono- or di(C_1-4alkyl)aminoC_1-6alkyl;

provided that when L is a radical of formula (a-9) then R11 is other than hydrogen.

2. A compound as claimed in claim 1 wherein L is a radical of formula (a-1), (a-2), (a-3), (a-5), (a-7), (a-8), or (a-10), wherein R¹⁰ is hydrogen, C_1-6alkyl, or di(C_1-4alkyl)aminoC_1-6alkyl.

3. A compound as claimed in claim 1 wherein L is a radical of formula (a-3) or (a-9) wherein R¹¹ is hydrogen, C_1-6alkyl, amino, aminoC_1-6alkyl or di(C_1-4alkyl)amino-C_1-6alkyl.

4. A compound as claimed in claim 1 wherein wherein L is a radical of formula (a-4) or (a-6) wherein R⁸ and R⁹ are each independently hydrogen, C_1-4alkyl, or aminoC_1-6alkyl.

5. A compound as claimed in claim 1 wherein the compound is

4-[[(1,1′ -biphenyl)-4-yl]phenylmethyl](1,4′

-bipiperidine),

4-[[(1,1′

-biphenyl)-4-yl]phenylmethyl]-1-piperidinepropanamine,

N-[3-[(1,1′

-biphenyl)-4-yl]-3-phenylpropyl]-1,3-propanediamine, and

the acid or base addition salts, the stereoisomeric forms, the N-oxides, or quaternary ammonium derivatives thereof.

6. A compound as claimed in claim 5 wherein the acid addition salts are 1,2-benzisothiazolone (BIT) salts.

7. A biocidal composition comprising one or more inert carriers and, if desired, other adjuvants, and as active ingredient a biocidally effective amount of a compound as claimed in claim 1.

8. A biocidal composition as claimed in claim 7 further comprising one or more other active ingredients selected from bactericides, fungicides, insecticides, acaricides, nematicides, and herbicides.

9. A method of controlling micro-organisms by the application of one or more compounds as claimed in claim 1 to said micro-organisms.

10. A composition comprising a compound as claimed in claim 1, and another active ingredient, in quantities producing a biocidal synergistic effect, and a carrier.

11. A composition according to claim 10 wherein the other active ingredient is a fungicide or a bactericide.

12. A process for preparing a compound of formula (I) wherein

a) an organometallic derivative of an intermediate of formula (II), wherein halo'"'"' represents chloro, bromo or iodo, is reacted with an intermediate of formula (III), yielding compounds of formula (I-a), defined as compounds of formula (I) wherein X is hydroxy and the dotted line does not represent a bond;

b) an intermediate of formula (V) is N-alkylated with an intermediate of formula (IV) in a reaction-inert solvent and, optionally in the presence of a suitable base, yielding compounds of formula (I-c-1), defined as compounds of formula (I) wherein X is hydrogen and the dotted line does not represent a bond and L¹ represents a radical of formula (a-2), (a-3), (a-6) to (a-10) wherein A¹ is a direct bond;

c) an intermediate of formula (VI) is reacted with an intermediate of formula (VII) in a reaction-inert solvent, yielding compounds of formula (I-d), defined as compounds of formula (I) wherein L² represents a radical of formula (a-6) to (a-10) wherein A¹ is C_1-6alkanediyl;

said intermediate of formula (VII) has one of the following structures;

wherein in the above reaction schemes the radicals L, R¹ to R¹⁰ are as defined in claim 1 and W is an appropriate leaving group;

d) or, compounds of formula (I) are converted into each other following art-known transformation reactions;

or if desired;

a compound of formula (I) is converted into a pharmaceutically acceptable acid addition salt, or conversely, an acid addition salt of a compound of formula (I) is converted into a free base form with alkali; and

, if desired,