Note: Descriptions are shown in the official language in which they were submitted.
5-13321/=
Halomethyltriazoles
The present invention relates to novel l-halomethyl-lH-1,2,4-triazoles
and to a process for their production. The invention further relates
to a novel process for obtaining the starting compound, l-hydroxy-.
methyl-lH-1,2,4-triazole.
The l-halamethyl-lH-1,2,4-triazoles have the general formula I
,N=
: 2 \ ~
wherein Hal is chlorine, bromine and iodine.
.
The compounds of formula I are employed as starting compounds for
obtaining triazolylmethyl phosphonates of the formula II
~ ~ CH2 ~ N\ ~ (II),
wherein each of the radicals Rl independently of the other is phenyl
or Cl-C~alkyl, or triazoly].methyl phosphonium compo~mds of the
~ormula -.LII
2 ~ C~12 N\ I ~lal ~ (.tII),
wherein each of the radicals R2 independent:Ly o:t one another is
yhenyl or CL-C4aLkyl which i8 msul)stituted or subst:;tuted by hydroxyl,
and Hal is as definecl for formula I.
5-l3321/=
: Abstract of the Disclosure
: Halomethyltriazoles
. . . _ .
The invention discloses halomethyltria~oles of the formula I
,N=-
Hal - CH2 - ~
. =
wherein Hal is chlorine, bromine and iodine.
.
The compounds of formula I are important intermediates for obtaining
highly active plant fungicides.
These compounds are used in turn for the production of fungicidal
phenylethylenyltriazoles of the formula IV
Ar\ /N=.
~ C -- CH - N ¦ (IV),
R \.=N
wherein Ar is phenyl which is unsubstituted or subs-tituted by Cl-C4alkyl, Cl-C4-
alkoxy, cyano, nitro, trifluoromethyl, or by one to three halogen atoms, and R
is hydrogen, Cl-ClOalkyl, C2-C5alkenyl, C3-C8cycloalkyl, Cl-C4alkyl which is
unsubstituted or substituted by C3-C8cycloalkyl or phenyl which is ~msubstitutedor substituted by halogen, Cl-C~alkyl or Cl-C4alkoxy, ancl plant fungicidal 1-(2-
phenylethyl)triazoles of the formula V
N=.
Ar - CH - CH2 - N\ ¦ (V),
R .=N
wherein Ar and R are as defined for fo-rmula IV.
The compounds II, III and IV, as well as the method of preparing the
compounds V, form the subject matter of Canadian Patent Application No. 397,945.
The compounds of formula V are described in Canadian Patent No. 1,133,492.
The preferred compound of the formula I according to this invention is
l-chloromethyl-lH-1,2,4-triazole.
The compounds of the formula I are obtained by the process of this
invention by reacting l-hydroxymethyl-lH-1,2,4-triazole of the formula VI
/N=.
HO - CH - N l (VI),
wlth a h~logenating agen~, and treatlng the resultant hydrohal:ldes ol the
fo~mul~ VII
/N=~ .
2 \ ~N (VII),
~,
wherein Hal is as defined for formula I, with a base.
Suitable bases are strong inorganic hydroxides such as sodium and
potassium hydroxide.
Suitable halogenating agents are: phosgene, thionyl chloride, thionyl
bromide, phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride,
phosphoroxy chloride or hydriodic acid. Preferred halogenating agents are
thionyl chloride and thionyl bromide, as the by-products formed are gaseous
and therefore do not influence the reaction. The iodine compounds are
conveniently obtained from already halogenated compounds by reacting these latter
with hydriodic acid.
A further method of obtaining corresponding chlorides, bromides and
iodides comprises reacting compounds of the formula VI with the corresponding
trialkyl silyl halides.
The halogenation reaction is normally carried out in inert solvents,
e.g. hydrocarbons such as hexane, cyclohexane, benzene, toluene or xylene, or
ethers such as diethyl ether, tetrahydrofurane, dioxane or xylene or dimethoxy
ethane. When using liquid halogenating agents, it is frequently possible to
dispense with a solvent entirely. The reaction is then carried out in an
excess of reagent, e.g. thionyI chloride or thionyl bromide.
The l-halomethyl-lH-1,2,4-triazoles of the formula I are compounds
; which are unstable at room temperature and also at 0C. Surprisingly, however,
it has been found that solutions of l-halomethyl-lM-1,2,4-triazoles Oe the
Eorm~lla I ln acetonltrLle can be s~ored Eor months without clecomposltion.
The start:Lng compound oE the eormllla VL Is known erom Kllim~
Geterosikl. Soedl., 1980~ 251 (English translfltion: Chem. ~leterocycl. Comp.
_.
1980, 189). In the process descrlbed thereln, the hydroxymethyl
,~,.
triazole is prepared using aqueous formalin solution.
Surprisingly, it has now been found that higher yields can be obtained
by carrying out the synthesis using paraformaldehyde in a non-aqueous
rnedium. This process also cons~itutes an object of the invention~
In the process of this invention, l-hydroxymethyl-lH-1,2,4-tria~ole
is prepared by reacting lH-1,2,4-triazole in a non-aqueous medium, in
the presence of catalytic amounts of a base9 with paraformaldehyde.
The reaction may be carried out in the presence or absence of an
inert solvent.
Suitable solvents for this process are inert organic compounds, e.g.
ethers, preferably containing 2 or more oxygen atoms, such as dioxane
or dimethoxy ethane. The reaction is carried out by boiling the
reaction mixture under reflux. It is particularly advantageous~ how-
ever, to carry out the reaction without a solvent in the melt of the
reactants. The temperature is in the range from 40 to 150C~ with
the preferred range being from 60 to 100C.
Suitable bases are: hydroxides such as sodium or potassium hydroxide,
carbonates such as sodium or potassium carbonate, or amines such as
triethylamine, quinoline and pyridine.
The following Examples illustrate the invention in more detail.
Pressures are given in milllbars tmb).
.xam ~ 1: Preparation of l-chlormethyl-lH-1,2,4-triaæole
hydrochlorLde
A melt of 195.3 g (1.74 moles) of l-hydro~ymethyl-lH-1,2,~-triaxole
is added dropwise over 1 1/2 hours to 600 ml oE thionyl chloride.
Vigorous evolution of gas ensues and the reaction mixture begins to
boil. After the melt has been completely added, the reaction
mixture ls stirred under reflux for a further 2 hours and then cooled.
-- 5 --
The precipitated yellow l-chloromethyl-lH-1,2,4-triazole hydrochloride
is isolated by filtration and washed with two 300 ml portions of
diethyl ether. Yield: 272 g (93.5 %). Melting point: 120-127C.
C H ClN ~ HCl (154)
cal.: C 23.40 %; H 3.27 %; N 27.29 %
found: C 23.40 %; H 3.5 % ; N 27.30 %,
H-NMR (CD30D): ~= 9.77 (s; lH, 5-CH); 8.55 (s; lH, 3-CH);
5.9 (s; 2H, CH2-Cl) and 5.06 (s; lH, HCl) ppm.
Example 2: Preparation of l-chloromethyl-lH-1,2,4-triazole
With efficient stirring, 80 g of sodium hydroxide in 250 ml of water
are added dropwise to 240.6 g (1.44 moles) of 1-chloromethyl-lH-1,2,4-
triazole hydrochloride in a mixture of 600 ml of water and 400 ml of
chloroform. The reaction mixture is saturated with sodium chloride
and extracted three times with chloroform. The chloroform extracts
are dried and concentrated. Fractional distillation of the residue
yields 156.2 g (83.05 %) of 1-chloromethyl-lH-1,2,4-triazole w;th
a boiling point of 52-54C/0.27 mb.
H-NMR (CDC13): S = 8.8 (s; lH, 5-CH); 8.3 (s; lH, 3-CH)
and 6.3 (s; 2H, CH2Cl) ppm.
~xample 3- Preparation oE 1~ ~ roxymethy'1.-1~1~1,2,4-~riazole
__ __ _ _ _
mlxture o~ 140 g (2 mo'Les) oE lH-1,2,4-triazole, 60 g oE parn-
~ormaldehyde and 'L.5 ml oE triethylamine is hea~ed Eor ~ hours to
Eorm a clear melt, which congeals on cooling. Recrystallisa~ion
from acetone aEEords 195.3 g (98.5 %) oE l-hydroxymethyl-lH-1,2,~l-
triazo'le with a melting point of 65-67C.
C3H5N30 (99.1)
cal.; C 36.3 %; H 5.0 %; N 42.4 %
found: C 36.0 %; H 5.0 %; N 42.4 %.
H-NMR (CDC13): d = 8.47 (s; lH~ 5-CH); 8.0 (s; lH, 3-CH);
7.35 (s; lH, OH) and 5.67 (s; 2H, CH20) ppm.
