Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
The present invention relates to certain new pyrimidyl-carbinols
which are useful as intermediate products ~or the preparation of benzyl-
pyrimidinylalkyl-ethers, and to a process for the preparation of the
pyrimidinyl-carbinols.
The present invention now provides, as new compounds, the
pyrimidinyl-carbinols of the general formula
HO - Cll - R
~ ~II)
N~N
in which
R represents isopropyl, isobutyl, tert.-butyl, n-pentyl, n-hexyl,
optionally methyl-substituted cyclopentyl or cyclohexyl, or phenyl which is
optionally substituted by fluorine, chlorine, methyl, methoxy or trifluoro-
methyl.
Formula (II) gives a general definition of the pyrimidinyl-
carbinols according to the inventionO
-1-
The pyrimidinyl-carbinols of the formula (Il) have not hitherto
been described in the literature. Ilowever, they can be obtained in a known
manner by a process in which pyrimidine halides of the general formula
~ (IV),
in which
Z represents halogen, particularly chlorine or bromine, are
reacted with aldehydes of the general formula
O = CH - R ~V),
in which
R has the meaning given above,
in the presence of a diluent and in the presence of an al~ali metal-organic
compound.
Inert organic solvents are preferred diluents for the preparation
of the pyrimidinyl-carbinols of the formula (II). These include, as
preferences, those solvents which have a low melting point, such as ethers, for
instance diethyl ether of tetrahydrofuran. The reaction is preferably carried
out using mixtures of these two ethers.
The preparation of the compounds of the formula (II) is
~'
~'7~'7~7
effec-ted in the presence of an alkali me-tal-organic compound.
Alkali metal-alkyls, such as n-bu-tyl-lithium, are preferably
employed for -this purpose; alkali metal~aryls, such as phenyl-
lithium, can also be used.
In carrying out this process, the reaction temperatures
can be varied within a particular range. In general the reaction
is carried out at temperatures between -150C and -50~C, preferably
be-tween -120C and -80C.
This process is preferably carried out under an inert
gas, such as, in particulax, nitrogen or argon.
In carrying out this process, 1 to 2 moles of aldehyde of
the formula (V) are preferably employed per mole of pyrimidine
halide of the formula (IV). The alkali metal-organic compound is
advantageously used in an excess of 5 to 75 mole per cent, pre-
ferably of 10 to 50 mole per cent.
The pyrimidine halides of the formula (IV) and the alde~
hydes of the formula (V) are generally known compounds of organic
chemistry.
The isolation of the compounds of formula (II) is
effected by hydrolysing, for e~ample with saturated ammonium
chloride solution or with water, the alkali metal alkanola-te (for
example lithium-alkanolate) which is first formed in the reaction.
The further working-up is then effected in the customary manner.
The pyrimidinyl-carbinols of the formula ~II) represen~t
generally interesting intermediate products, for example for the
preparation of the compounds of the formula (I), as shown below.
~ore particularly, the compounds of formula II according to the
present invention may be used for the preparation of benzyl-
pyrimidlnylalkyl-ethers oE the formula (I),
x2 ~ CH2 ~ O - CH - R
xl ~ (I)
~N
or acid addition salts or metal salt complexes thereof, by reaction
with a ben~yl halide of the general formula
~ CH2 - Hal (III),
in which
Xl, x2 and X3 are selected independently and each represent
hydrogen, halogen, alkyl, cycloalkyl, alkoxy, alkylthio,
halogenoalkyl, halogenoalkoxy, halogenoalkylthio, cyano,
optionally substituted phenyl, optionally substituted phenoxy,
optionally substituted phenylalkyl or optionally substituted
phenylalkoxy, and
Hal represents halogen,
in the presence of a solvent and, if appropria-te, in the presence
of a strong base or, if appropriate, in the presence of an acid-
binding agent, and, if required, a sui-table acid or a suitable
metal salt is added on-to the resultant compound.
The benzyl~pyrimidinyl-alkyl-ethers of the formula (I)
and the acid addition salts and metal salt complexes -thereof have
powerful plant growth-regulating and fungicidal properties.
-- 4 --
'78~
Example 1
HO - HC - C(CH3)3
~ (II-l)
N N
225 g of 5-hromopyrimidine were dissolved in 1.5 litres
of absolute tetrahydrofuran/l,000 ml of absolute ether, and the
solution was cooled to -120C. 250 ml of 50% strength n-butly-
lithium (in n-hexane) were added dropwise to the solution, during
the course of 2 hours, at an internal temperature of -105C to
-115C. The mixture was further stirred for 1 hour at this tem-
perature. 309 ml of trimethylacetaldehyde were then added drop-
wise during the course of 2 hours. ~he reaction mixture was then
further stirred for 4 hours at this temperature. The reaction
mixture was allowed to warm up to room tempera-ture overnigh-t, and
83 g of ammonium chloride, dissolved in a minimum quantity of
water, were then added to it. The aqueous phase was separated off,
and the organic phase was washed twice with saturated aqueous
sodium chloride solution, dried over sodium sulpha-te and concen-
trated. 155 g (S6% of -theory) of 5-(1-hydroxy-2,2-dimethylpropyl)-
pyrimidine of melting point 94 - 96C were obtained after recry-
stallisation of the residue from acetonitrile.
Converslon of the_ yrimidine-carbinol in-to a compound_of
formula (I)
. . . _ __
Cl ~ CH2 - O - CH- C(CH3)
(~ (1)
N~_,N
-- 5 --
~'7~77
200 ml of 33% strength aqueous sodium hydroxide solution
were added -to a solution of 16.6 g of 5~ hydroxy 2,2-dimethyl-
propyl) pyrimidine, 32.2 g of 4-chlorobenzyl chloride and 6 g of
tetrabu-tylammonium bromide in 200 ml of toluene. The reaction
mixture was stirred vigorously at room temperature for 18 hours.
The aqueous phase was separated off, and the toluene
phase was diluted with toluene~ washed four times wi-th water and
once with saturated aqueous sodium chloride solution, dried over
sodium sulphate and concentrated. The oleaginous residue was
dissol~ed in ether/hexane, and the solution was treated with
hydrogen chloride gas. The resulting crystalline precipita-te was
filtered off under suction and rinsed with ether, and ethyl
acetate/ lN sodium hydroxide solution was added to i-t, the free
base again being formed.
20.3 g (70% of theory) of 5-[1-(4-chlorobenzyloxy)-2,2-
dimethylpropyl] pyrimidine of melting poin-t 77 - 78.5C were
obtained after recrystallisation from hexane.
The following compounds oF the formula (II) were obtained
by methods analogous to that described in Exarnple 1
Table 2
H - O - CH - R (II)
N
-- 6 --
'7~7~
Example
No. R Physical constants
II-2 -CH(CH ) boiling point:
3 2 80-82C/0.02 mm Hg
II-3 ~ mel-ting poin-t:
85-87 C
II-4 ~ Cl
II-5 -(CH ) CH boiling point:
2 4 3 118 25C/0,005 mbar
