Note: Descriptions are shown in the official language in which they were submitted.
3~ii7
. .
This application is a division of Canadian Patent
application n 291,003 filed on November 16, 1977.
: The present invention relates to new derivatives of
;. 1,2,~-triazole that can be used as intermediate compounds in
~- the preparation of the new esters disclosed in the parent ap-
- plication n 291,003, which esters contain a phosphorus atom in
their acid part and are derived from 5-hydroxy ~or 5-mercapto~)-
1,2,4-triazoles.
~ The invention also relates to a process for the pre-
. paration of these new derivatives of 1,2,4-triazole.
. The esters of pentavalent phosphorus derived from new
5-hydroxy (or 5-mercapto)-1,2,4-triazoles which are disclosed
in the parent application are substituted or unsubstituted
in position 1 and substituted in position 3 of their nucleus.
These esters can be used for cQmbatting pests such as orthoptera,
aphides, diptera, coleoptera, lepidoptera, acari and nematoda.
Amongst the thiophosphates derived from 3-hydroxy-1,
~,4-triazole variously substituted in positions 1 and 5 of the
ring, many have proved to develop an insecticidal activity.
.; 20 Amongst these., two products have been commercialized for the
fight.against insect pests: ~
:~ Triazophos: ~ ~ (C2Hs)2
<N
. N /
~ 16H5
.~ an insecticide which acts by contact and ingestion, commer-
cialized by the HOECHST Company and described in South African
Patent No. 6.803.471; and
Diethyl-(l-isopropyl-5-chloro-1,2,4-triazo].e-3-yl)
Phosphoro-thionate ~MiFal) ~ produced by 'Ciba-Geigy':
;~
.. . . ~
`. ' , : .
`~;`
:
- P - (OC2H5)2
Cl ~ ~ ,
CH tCH3)2
and described in German Patent No. 2,260,015, and which is
effective against insects in the soil..
- Lesser attention has been given to the derivatives of
5-hydroxy-1,2,4-triazole, such as diethoxy-phosphoro~thioate of
1-methyl-3-phenyl-5-hydroxy-2,2,4-triazole of the formula:
(C2H5O)2 ~P-O ~ 6Fl5
CH3
claimed in U.S. Patent No. 3,6~9,500.
The new esters of pentavalent phosphorus which Eorms
the subject ma~ter of the parent application are of the general
formula ~
: Rlo R4
~ _-P-X ~ / (I)
., ~ ,
: R
` wherein
R = alkyl with ~rom 1 to 5 carbon atoms;
R2 = oRll R1, C6H5, NHRl, N (Rl)2;
X = O,S;
R3 = H, alkyl with from 1 to 5 carbon atoms, C6H5,
.~
benzyl, alkenyl with from 2 to 6 carbon atoms,
alkenyl with from 2 to 6 carbon atoms; and
R4 = halovinyl, polyhalovinyl, vinyl, vinyl substituted
with phenyl, alkyl with Cl-C4, O-alkyl with C1-C4,
or S-alkyl with Cl-C4
--2--
~, ,
.-. ~ : " . .
~:
: ` -
': ~
haloalkyl, acetyl, cyclohexenyl, benzoyl,
-CH-R5 ~wherein R5 = OH, 0-C-R1, 0-3-vinyl, -o-~-
~poly)-halovinyl,
~...................... O
~ -0-C-haloalkyl, Cl, S-Rl, 0-R , N(Rl)2, NHRl~,
: 1l' ~5
: : - -C-CH2-SR , -CH- H2SR
These new esters exert an insecticidal action over a wide action
1~ spectrum, since they are very active against orthoptera, aphides,
diptera, coleoptera, lepidoptera, developing as well an acaricidal
and nematocidal action, and at the same time havlng a low toxicity
for warm-blooded animals. In some of the most active compounds
thls toxicity is far much lower than that of Triazophos or
analogous commercial compounds.
,. . .
The object of the present invention is to provide new
derivatives o~lj2,4-triazole that can be used as starting or
intermediate compounds in the preparation o~ the above defined,
.
new esters.
. 20 The new derivatives of 1,2,4-triazole according to
the present invention are of the general formula:
, . :
.~.~ .
~ R
X=<~
~. 3
; R
wherein:
, . .
X = 0 or S;
. ~ R3 = H, alkyl containing from 1 to 5 carbon atoms,
C6H5, benzyl, alkenyl containing from 2 to 6 carbon
atoms, or alkynyl containing from 2 to 6 carbon atoms;
and
-3-
, :. ,
~6~
; R4 - vinyl, halovinyl, polyhalovinyl, vinyl substi-
tuted by phenyl, alkyl containing ~rom l to 4 carbon
: ~ atoms, O-alkyl containing from 1 to 4 atoms, S-alkyl
containing from 1 to 4 carbon atoms, haloalkyl, acetyl,
cyclohexenyl, benzoyl, or a radical of the formula
-CH-R5, -CO-CH2-SRl or -fH -CH2-SR in which Rl=
CH3 ~ R
. alkyl containing from l to 5 carbon atoms and
R5 = OH, O-~-Rl, O-l-vinyl, O-I_(poly)-halovinyl,
O-~-haloalkyl, Cl SRl, ORl, N(Rl)2 or NHRl.
. .
The derivatives of 5-hydroxy (or 5-mercapto)-1,2,4-
triazole according to the invention, in which R3 is a phenyl
can be prepared starting from the ~ chloro ~ substituted
~formyldidenphenylhydrazines described in Italian Patent
No. 998,314. By treatment with ammonia and subsequently con-
~ densing the reuslting amino-derivative with phosgene or thios-
;~ : phosgene, according to the reactions:
-~ 20 C6H5-NH-N=f-R4+2NH3 ~ ~ C6H5-NH-N=f-R +NH4Cl
~ Cl NH2:
i ,
C6H5-NH--N=f -R4+CC12 ' ''~
:. NH2 N
.- C6E15
: one obtains the desired triazole which, in an alkaline medium, is
converted to the salt.
;. In the cases where R4 contains~a functional group, it
is possible to exploit various reactions per se well known in
organic chemistry for introducing other groups into the side
-3a-
. - . ,
.. . . .
: .
chain of ~he triazol-one (or thione) itsel~ ~see Ex~ 6 below).
Thus, from l-phenyl-3-acetyl-1,2,4-triazol-5-one, by exploiting
the typical properties of the acetyl group, by reduction o~ the
CO group, there was prepared the corresponding alcohol which,
by treatrnent with thionyl chloride, allowed the preparation of
the following compounds:
''
: CH3 IH3
CO CH-OH
N O ~ N /
: I I
C6H5 C6H5
: (3) (4)
.
CH3 ICH3
~ CH-Cl CH-Cl
0 ~~
; 20 6 5 C6H5
(5) (5)
. ' .
`' CH2 . , CH2-Br
: CH CH-Br
HN ~ Br2 ~ HN - <
< N / ~, ~ / N
t 1 H
6 5 C6H5
(6) (7)
6~
CH
1 3
CH-OCH3
.- HN
(~)OCH 3
, - -~O
;: . C6H5
(O,
,.:
CH
. . . 1 3
:` 10 CH-S-CH
(~) ~` 3
. 1~ 0 ~ ~N
~ fH3 N
C6~15
CH-Cl
HN / CH
C~E15 CU ,~.~ CH-N
`- (5) ~ O N/
: 20 ~6H5
~: . (10 )
: ~ f 3 - CH
~ ~ CU3
,' . C6H5
(11 )
.
:' .
--5--
.' ~ . . .
,, . , , -
. . ' ' ~
~7
; The derivatives of 1,2,4-triazole according to the
present invention in which R3 i5 an alkyl can be prepared
by condensing an aldehyde R4-CHo with 2~alkyl-(thio)-semicar-
bazide, followed by -treatment o~ -the (-thio)-semicarbazone
thus obtained with bromine in glacial acetic acid in order to
obtain the triazole which, in its turn, is -treated in an
;. alkaline medium as previously described, according -to the
reactions:
10R4-C~I=N-N - C-N~2 -~ Br2 ~ ~ R -f=N-N-C-N~l2 1 -~ r~
.. ~r
: . .
Y N ~R4
~N~ MaX
N _ NaOH _~
. X N
R
- The (supposed)mechanism of -the above-described
reactions is reported in Tetrahedron Le-tters 28 (1971) on
pages 2669 and following, in the cases in which R4= aryl
, and X = O.
~ It has been Eound thatif, on the con-trary, R4 is
: a vinyl group, this latter may also be attacked by bromine,
giving place to a sequence of addition and elimination reac-
tions. More particularly, when the starting aldehyde contains
. halogen atoms different from bromine in ~ position, these
may be substitu-ted by bromine atoms during the cyclization
reaction through a possible sequence of stages, as hereunder
indicated purely for exemplification:
..
--6--
! ~. `,
:
Cl~ ~ ~Br2 Cl `R3
C.CN-CH N-N-CO-NHz~ C=C~I C n L_CO_N
2 -HBr
-HBr
,.", ~ 3~
H C 1
¦ N~ \Cl
:- O N ~Br
Cl~ I ~ ~3 R -HBr
C-C-CH=N-N-CO-NH 2 ~ ~
Cl ~ H C-C '''
. N._ < - C.l
: ~ N /
~HBr R3
-HCl
,' '. ~ ~
. . t H~r
. -NCl
~ '"'` ,
Br R3 ~ .
C,C-~ 'H=N-N-CO-NH ~ Br2 Br ~ Br
C Br -HBr ~ N ~ ~ Cl
. ~ HBr // < , / N
-HCl R3
.
~ HBr
~ ~ .
-?- ~ -HCl
.. ,
:
~: ~
: ~HBr . ~HBr
. -HCl -HC1
'~, ~ ~ ~
Br ~r
::: Br Br R3 H I /
C~C-CH=N-N-CO-NH2 ~B~ N Br
~: 10 l3
.. : R
. Depending on the temperature conditions, the reaction
may be oriented (directed) towards the formation predominately of
one single cyclization product containing the sarne (halo) vinylic
. group of the starting aldehyde, or towards the formation of
: products or mixtures of products containing bromine atoms in the
vinylic positions of the derived triazole, as evidenced by
Examples a and 9 below.
The vinyl group may also be introduced into
position 3 of a 1-phenyl-1,2,4-triazole (5)-one (or thione) by
:
starting from l-phenyl-3-acetyl-1,2,4-triazole-$-one (or thione),
: as described in the first sequence of reactions performed on an
acetyl group tsee page 5, compound ~6)).
., :
In a more general manner, the derivatives oE 1,2,4-triazole accor-
cling to the present invention can be prepared by cyclisation of the semi-
,,, ~ .
. carbazones of the general formu].a;
. R3X
R -CH=N-N-C-NH2
wherein:
R3 - H; alkyl with from 1 to 5 carhon atoms; C6H5,
~ 30 benzyl, alkenyl, alkynyl;
.' R4 _ halovinyl, polyhalovinyl, vinyl, vinyl substituted
. with phenyl, alkyl, o-alkyl or S-alkyl; haloalkyl,
.' ~ ~i .
~ . -8-
; ~ ~
: , ,
. ~
3~7
` .
. CI13
. cyclohexenyl, acetyl, ben~oyl groups; - C~IR5
O O O
~wherein R5 - OH, O-C-alkyl, O-C-vinyl, O-~-(polyj-
, 11
halovinyl, -O-C-haloalkyl, Cl, S-alkyl, O-alkyl,
Pl . R5
N~I-alkyl, N(alkyI)2] ; -C-CI~2-S-a1kyl, -CI~-CH~-S-
alkyl;
~ 10X- O, S,
The cyclisation may be carried out in the presence of the ferric
chloride according to the reaction: R4
R3X
¦ R4-CH-N-N-C-N~I ~ 2FeC13 ~ X _ ~ N t2FeCl
: R3 +2HCl
The cyclization reaction herein descrihed allows one to obtain
directly the .triazolone ~or thione) in a state of high purity
even in cases wherein the R~ group contains olefinic double bonds
; 20 that may be attacked by bromine, and:so proves to be superior to
: ~ the other methods described above.
The reaction is carried out in a polar solvent, pre-
ferahly acetic acid, at boiling temperature.
- The characteristics of the 1,2,4-triazol-5-ones pre-
pared by one of the above descrihed methods, are reported in
Table I. ~ .
:~ ~
t
'
.
_g_
~ . ~
3~3
.:, ,
.,
TABLE I
1,2,4 triazol-5-ones prepared by means of the processes
described in the present invention and having the general
formula:
i~ H \ R
~' ~ / <`
.~, . ' ~ 0/ /
~ R3
',, 10
,.,. ... .... _.
Identifi- 3 ,m.p. Elemental analysis
,~, cation R R4 (C)
mark (*) C ~I
M theor. found theor. ~ound
.. . . .. __
7476 C6H5 COCH3 174-6 20.68 20.57
7478 C6H5 COC6H5 220-1 15.84 16.03
8262 C6H5 CH-CH3 149-50 20.47 20.08
, OH
8085 C6H5 CH-CH3 159-60 la. 78 18.77
. 1
8263 C6H5 CH=CH2 200 22,44 22035
208264 C6H5 ICH-CH2Br 177-8 12.11 11.47
' - Br
8265 C6H5 bCH-CH3 140-1 19.16 19.10
CH3 ~
8266 C6H5 ~CsH-C~I3 130-2 17.70 17.23
CH3 ~
- -8268 C6H5 CH-CH3 _ 20.85 20.56
~(CH3)2 HCl
8267 C6H5 ICH-CH3 140-2 22.75 22.57
- NH-CH(CH3)2
8269 C6H5 CO-CH2-S-CH 189-90 16.85 16.76
8254 C6H5 1CH-CH2-S-CH3 102-4 16.72 16.39
~' '
..
.` - -10-
.
i3
`'
,:.: ` ., ;
~ TABLE I (Cont'd)
:
Identifi- ~ ~..... Elemental allalysls
cation R R (Pc; -
: ~ (*) theor. found theor. found
8256C6H5 CH-CHz-S-CH3 145-6 _ __ 15.58 15.35
8255C6H5 COOC2H5 195-6 18.02 17.76
8258C6H5 CH2H 178-80 21.48 22.20
8259C6H5 CH2Cl 154-6 20.04 19.90
8260C6H5 CH2-OCH3 126-8 20.47 20.15
i 8270C6H5 OEIO 164-6 22.21 21.57
Br
CH3 C-C
8309 151-3 13.71 13.74
CH3 ~ Cl ture
Br 56%)
8088 CH3 ~r \Br 181-4 11.61 12.1-3
~ Cl
8310 CH3 CH=C \ 215-6 21.65 21.66
~ Br
8307 CH3 CH=C\ 211-4 18.85 13.99
. . Br .
CH3 CH=CH2 161-2 47.99 47.92 33.58 33.35
CH3 CH=CH-CH3 167-8 51.79 50.91 30ul9 30.01
CH3 CH=C(CH3)2 144-6 54.88 56.27 27.40 28.54
CH3 C(CH3)=CH2 168 9 51.79 50.85 30.19 29.33
CH3 C(CH3)=CC12 197-8 34.64 34.87 20.20 20.12
CH3 C(Cl)=CC12 201-2 26.29 26.64 18.40 18.42
` CH3 CH~C(OCH3)Cl 198-9 38.00 37.62 22.16 22.15
CH3 C( Br)=CH-CH3 188-9 33.05 33.96 19.27 19.38
CH3 C(Cl)=CH-CH3 191-2 41.51 40.89 24.20 23.49
,
. ., . .:
37
~ ` , ,
'.':
TABLE I (Cont'd)
. .
Iden- A _ _ __ . ___.. _____ . ~ ._.. ._
tifi- m.p~ Elemental analysis
cation R3 R4 (C)
mark (*) _ _
- M theor. found theor. found
.~. . - __
CH3 C(C2H5)=CH 146-7 61.51 51.6921.52 21.74
CH(CH3)2 CH=CC12 164-5 37.8638.70 18.92 19.30
2)3 3 CH=CC12107-8 40.70 40.73 17.80 17.90
, ~CH2)3-CH3 OEI=CH-CH3 90-1 59.6458.82 23.18 23.04
-CH(CH3)2 CH=CC12172-3 40.69 41.69 17.79 18.25
(*) The melting points are not correc-ted.
The 1,2,4-triazol-(5)-ones (or thiones) in the presence
of a base are converted into their alkaline salts which, by react-
ing with the wuitable (thio)-phosphoryl chloride, give the
triazolyl-(thio)-phosphate of the general formula (I):
H R4 R4
~ 20 X ~ ~ + Na OH - ~ Na X
:' . 1 1~,
~ R3
:, , .
~ ~aX- ~ ~ + P-Cl / P-X ~ NaCl
R3 R3
(I)
~ .
According to this procedure, the 0,0-dialkyl-0-(1-R3-
30 3-R4-1,2,4-triazol-5-yl)-thiophosphates reported in Table 2 were
prepared-
-12-
3E~7
,' ` :' `
~ ~ _ABLE 2
R4
~lo - p _ o ~ M
^ R2 l3
R
, _ _ _ __ ,, __ , _,_ _~,_ . . .....
identi-
fica- 1 2 3 4 _ El~ ENTAL_ANALY ,IS
Mark R R R R C H N S
M heor.found theor.found -theor.found theor.found
_ _ , _ , .
7490 C2H5 C2H5 C6H5CC-C6H5 54.6 53.6 4.8 4.6 10 9.9 7.69 8.00
; 7650 C2H5 C2H5 C6H5CC-CH3 9.O 9.1
7852 C2H5 C2H5 CH3C(Br)-
; C~r2 23.3 24.6 2.8 2.9 9 9.1 6.9 6-.9
Mre 44X( C2H5 /X2H5 CH3 C¦Br)~
see ~ ~C12
; 7853 \ C2~l5 C2H5 & H5 ,OEI-CH3 47.1 47.15.6 5.8 11.7 10.2 8.9 8.4
~H
8084 C2H5 ~X2H5 C6H5 ,H-CH3 48.1 48.1 5.65.5 10.5 10.8 8 7.7
XOCH3
8086 C2H5 C2H5 C6H5 _H-CH3
~-- }CO- 42.5 38.8 4.1 3.98.7 7.1 6.6 5.6
. ~H-CC12 .
8089 C2H5 C2H5 OEl3 3r2 21.1 21.5 2.62.5 8.2 8.1 6.2 6.5
8167 C2H5 C2H5 C6H5 ,H-CH3 48.5 48.4 6.05.9 11.3 11.4 8.6 8.3
XH3
8169 C2H5 C2H5 C6H5 CH3CH2 44.9 45.2 5.0 5.1 10.5 10. 5 16.0 L5.0
8170 C2H5 C2H5 C6H5 ~HCH33 46.5 45.8 5.7 5.7 10.8 10. 6 16. 6 15.5
8171 C2H5 C2H5 C6H5 ,H-CH3 49.9 48.8 6.6 7.0 14.6 13.4 8.3 7.3
l (CH3)2
~8173 ¦C2 5 ¦CC~H5 C6H5CH-CH~- ~44. 13.1 ~5.5 ¦ .5 11.4 ¦ 0.4¦1;.9 ~4.0
-13-
, ~ , , '' , .
' ~ ~
3~7
. .
.
1~1 ~1~I C~ ~' N r~ co ~ ~ cO
~ ~~r o ~co r~ o ~1 o ~ o ,~
r~r~co r~ coco r~co o cn o ~ co o r~ co
~1 ~1 ~1
:. .
o,1 ~ r~ r~ r~ o ~D
r cnr~ ~ ~o ro u~ o u) cn ~
.
o~cocn r~ coo~ coo~ 1 ~I cn o o~ cn
____ .
nco ~ r~ N ~O O ~D t~
O O00 ~U~ CO O ~D ~ ~ ~ r~
.. ... .. . . . . . . . . .
,
~ ~ ~ r o n ~ o~
cn~r r~~o r~ o cn r~) ,1 ~r oo
~1 0 N cn
' _,~r)
. . .
O ~ U~ ~ ~
-- q~co ~ ~ N LO ~D ~O ~O
CO ~ ~
cn l~co n ~ ~ co ~- N 10 ~0 O ~ N
~I
e~ co ~ CCI r~
~ NcoU~ ~ ~)r~ ~r ~ ~ ~I cn N cn N
:. ~~ocn ~r ~ N CO10 .-1 In cn ,1 o
~1 ~ ~ N ~ ~ N t~
: m
:, ~ ~ C)
N N _ 111 N
: ~, ~1 -1 N ~ 1`'1 m ~
C~ o
NU) ~ ~)N ~ Nt~C ) C) O m N
~1 x ~ ~ 11~ ll~1 11 o N I I C) ~1
N m m ~ ~ x -- o
m o m ~ -- m -- m -- m m m m m m m
.. . . _ .
N
m~'
O ~ ~ m $ $ $ m m ~ m ~ ~N X
r~
m
m m m ::q m ~ m I $ m m m m m m
N N N N N m N ~I N N N N N N N $
~ ~J N C.) I C~ ~) C ) C_) O U
O O O O O O O O O O O O O O O O
- r~
5:
$ m m m m m m c~ m m m m m m m .
N N N ~ N N N I N N N N N N N $
~ r~ ,I co o cn o co ~ f~l ~o cn N r~ cn o cn
r~ In ~ o Lt~ o ~r cn cn r~ ~r ~ co ~ ~ ~r
CO CO CO CO CO Co Co CO CO CO CO CO CO CO
.... ... _ . _ ,.__
--14--
~,,
---- . _
o~ o0 ~ ~r oo ~ O O ~
I' a~ ~ ~~ ~ ~, ~ o
. ~ r O~ O N~D ~1I D ~r
.
I~ I_ O~D ~C'~ ~
~ In O ~
~o o ~o
.
~D ~ ~O ~ ~ Ln
:; ~D CO O~ 0
~ o o ~ o
:
...
-- .
, o ~u~ a~ ul ~ oo ~
;
o ~
co ~ ~ ~r
~I` O ~D 1`
.1 ~ ~ ~ ~~ ~ e:r
. m x ~
E~ ~ m ~3
U ~ C) U U~ U U U
- U O UU ~ U~ ~
Il 11 11 11 11 11 11 P~ 11 11 11
xm
u c~ u u ~ c) -o m - c) u - o
~ . . .. .
~ .
~ U U ~
~ _ U
U U
U U U
~~ U U U
U I U U I ~ U
- o o o o o oo o o o
. .
u ~ 1u o u ~ u
,
o o r-- ~ Lr) I` co ~ cn ~r
-- - - - - ; - - - - - - -
f~ -15-
;3~
The compounds of this invention are endowed with a wide
~ action spectrum with respect to numerous species of parasitic
; arthropods, as clearly evidenced below in TABLE 5. Because of
:`. this important property they offe;r a practical advantage over
- most known insecticides. Moreovex, they are scarcely toxic to
warm-blooded animals in spite of their activity against the arthro-
pods. The LD on albino rats administered orally, proved to be,
for compound M 8174, greater than 1200 mg/kg. By way of exarnple,
:,
: the absolute harmlessness verifided in rats with a representative
mixture M 7852, in a dose of 800 mg/kg, has been shown in Table 3
.`. ~y comparison with values of LD 50 characteristic for two com-
mercial triazolyl-phosphoric insecticides.
For a still more intensive comparison of the insecti-
cidal activities of the new compounds of the present invention,
we have synthesized the material claimed in V.S. Patent No.
3,689,500, also endowed with a low toxicity towards mammals. Of
this material ~M 8172) we have estimated the effects on various
arthropods at decreasing doses, together with effects shown by a
. representative compound of the class described by us in this in-
vention (M 817~). The results, recorded below in TABLE 4, indicate
a significantly better activity of compound M 8174 on representa-
tive species of the orders of orthoptera, lepidoptera, coleoptera,
diptera as well as against nematoda and acari, especially at
lower dosages.
From the results reported in TABLES 4 and 5, it is
. evident that the compounds of the present invention are very
effective as insecticldes against orthoptera, aphides, diptera,
coLeoptera, lepidoptera as well as being effective as acaricides
and nematocides. Moreover they are far less toxic toward warm-
blooded animals than Triazophos and Miral (cf. Table 3).
-16-
:
.
T A B L E 8
~ 10 Mortality % per ge on rat (administered by mouth) at the
: indicated doses.
- --~
Compound Dose mg/kgMortality % ge
~ M 7852 (mixture, see Table 2) 800 0
; Triazophos
~; (reference compound) 8~ 50
: Miral ~
(reference compound) 60 50
,,~ ,
, ~ : .
. ~ ,
.~
t ` ' .
30
-17-
- - . : .. ~ :
,
. ' - '
`~
R ~ oO co
",, ~
'" ~ ~ g
., ~ ~ ,1
'.' ~ ~
o
~_ ~1
~o~
,., ~o
:'. ,~
:' .. ~
a) .~ ~.
O O o o
., ~o ~1 ~
. ~ ~ o
~: . o` ~1
.''' ~ . ~ o g
~ o
~ o
';~ ' o ~ .
o
~ o~
. ~ ~Lr) o
.'' ' O ~\Oo
~ o` ~o ~o
,`.' '~ ~
o~ o o
.: O O ~ O N
1~) ~
.' o\O ~ ~ O O
'. ~:1 O` ~l r-l
.'~
~N~`i
~:~ ~ ~8~
o
--18--
::
~ .
:~ o
`p
- . ~ ~ ~ ~ ~' + + + + I+ -~ I+ I I +
~ dP U r-l O
~ a~ ~ ~ . ... ._ .... __ _ ,.
U~ I ~ 1~
n~ o h--
. h--I ~ O + + + + + + + + + +
n~ O 0~,O
~+l E~ ++++++++++
4~ ~
O ~ .. ___._. _ .... _._
u~ h
~ O ~ O
~ + +1~-+ I +1+1+ + +1
.:: a) ~u~ o + + -~ +
Q. O h
U~ (1~ o
. ~P~ . ._.. _
~a cn O
~ a~
O ~~1
~rl o IJ
h ~ ~ O+ + + + + I + + +
~1 O o\
11 ~ r-lI + + + + + -1- + + +
+
~ . ~
- ~rl >~ ~
t~ ~~1 0
rl OP
t~ + + + + + 1_
t~l ~)h o + + 1+ ¦+ + + ~ I ~ +~ ¦
h .IJ o
a~ o ~ . __.... _ _ _ _ ...... __ _ _
~
. ~ ~1 O O + -1- + + + + +
E~ O Q, o\O + + I
~o\ U~ ~1 + + -~ + + + +
1:'1 o
11 O
m u, 0,0
: ~ ,¢ ++ m ''. ++1+1+ +1+ + ~ +
~ o
r~ .~ ~1 _ - ....
rd h
O ++++++++++
. o`P ++++++++++
~ ~ .
'. O ~
. U ~I h . _ .. . ___
Ei
~ + + + +
,, u~ O ~ ~ + -1-1+ +1+11 +1
: ~1 0 o ~ + + + +
., o ~ o\ O
C~ ._ ____ .
; a) ~ I rd ~
~ Q) o ~ E3
~ ~ + + +
;~ u ~1 +1 + + +
' loH ~ l m ~
. . ~ ~ ~ .. _ __
h
O
.. . _
:~ t) ~ 4-1 ~ O ~, ~ o
O ~ E; (d o~
. ~ . E~ O
O o r~) ~ ~ o ~ ~ ~ ~ o' oo 1~ er
0 ~1 ~1 ~1 ~1 0~ 0 ~
. -19-
:
6~
- . , .. ., .~
'~, .~ o~O + + ~ + + + +
~ ~ ~ + + + + ~
. .. . . . . . ~
: m
~ ~ ~ +++++++I++
. ~
~ ~ `0~' 1 +l ~+-~1 + +
~ ... .... _ ._
, .
,~, 0~l
.'` ~1 :~ +1+++++1++++
.. ~ . .. ... .... ... _
. ~ ~
E~ . ~ \o +++I+++ +++
~ - .. . .. _
: ~ , ~ +'+++++++++++,
_ . ... .. .
:: ~
' ~ ' ~ ++11 +1++1++ ~ + ~ .
._ O
a)
+++++++++t
'~ . ~ ++++++++++
. ~ ~ . _ ... ,. _ ..
~ ~ ~ ' ~r '
~ o r7 ~D ~9 0 a~ ~ ~ ~ ~ o co ~
Q u:~ co o ~ ~ ~ co o ~ ~ r n),
. ~ . - . ..... .. ._ .. _ _ .
-20- .
,
r ~ 31L 1~ 6 3 ~
` In order still better to illustrate the present inven-
tion a number of examples are given below.
EXAMPLE l
Preparation of l-phenyl-3-acetyl-l,2,4-triazole(5)-one:
-N}l4
C6H5-NH-N=f-CO-CH3l 2NH3 _ _
Cl
(1~
.- ~ COC12
10` C Hs-NH-N~f-cocH3
- NH - 2HCl
(2) CH
CO
HN ~
_ ~ N
N / (M7476)
C6H5 '
(3)
80 ml of an aqueous solution of NH3 (32% b.w.) (1~32
moles) were admixed with 500 ml of ethanol. To this solution
60 g (0.305 moles) of ~-chloro-~-acetyl-formylidene-phenyl-
hydrazine~ were added in small portions. Once the addition
was accomplished, the mixture was stirred for 2 hours at room
temperature. The insoluble ~-amino~-acetyl-formylidene-
phenylhyarazine (2) (48 g) was filtered and washed with 200 ml
of water (yellow solid, m.p. l82-l84C).
-~ - 42.5g (0.24 moles) o ~-amino-~-acetyl-formylidene-
phenylhydrazine were suspended in 300. ml of benzene. To the
suspension were added 57 ml (0.72 moles) of pyridine and then,
dropwise, 40 ml of a benzenic solution of COCl~ at 10 % concen-
tration (% b. vol.: 0.36 moles), while maintaining the tempe-
rature at 15-20C.
-21-
~ , :
1~ 3
:, . .
Once -the addition had ~een accomplished, the mixture was
stirred for 30 minutes at room temperature, and then 100 ml of
H2O and 10 ml of concentrated }ICl were added to it. The whole
was stirred ~or 2 hours at room temPerature. The insoluble
material was filtered on a Porous diaphrAgm and washed with ll2O.
25 y of 1-phenvl-3-acetvl-1,2,4-triazole~5)-one (3) were
o~tained. (m.p. 17~-176C).
EXAMPLES 2 - 4_
By operating as described in Example 1:
-- starting from ~-chloro-~-benzoyl-formylidene-phenyl-
hydrazine, l-phenyl-3-benzoyl-1,2,4-triazole(5)-one was prepared:
\\
O = ~ / N
IN (M 747~)
C6H5
-- startinq from ~-chloro-~-methylthio-acetyl-~ormyli-
dene-phenylhydrazine, l-phenyl-3-(methYlthio-acetyl)-1,2,4-tri-
azole(5)-one was ~repared:
~; I
\ N
~ / (M ~269)
O N
~ ! C6H5
-- starting from ~-chloro-~-carhoethoxy-formylidene-
phenylhydrazine, l-phenyl-3-(carboxyethylj-1,2,4-triazole(5)-one
was prepared
1.~ .
I~` 22
~ i3~3
': '
H ~ COOC2H5
.: ~< /
O N (M 825$)
C 6H
,~ `
' '
... EXAMPLE 5
.~
' 10 Reaction:
.~
~, HN CO-CH -S-CH
/ \\ 2 3
N t NaBH . _ _
, O
.. l
~ C6H5
. ,~
,~.
:.
~ OH
;:
~ H~ j\ CH CH2-~-CH3 (M al73)
:, //~ ,,Y '
O ¦ .
C H
6 5
~ 2.3 g of 1-phenyl-3-methylthioacetyl-1,2,4-triaZole(St-
: one, suspended in 40 ml of methanol, were treated dropwise with
~ a solution of 0.3 g of NABH4 in 5 ml of water.: The reaction
`- mixture was stirred for 1 hour, then was additioned with 0.5 ml
: of concentrated HCl and the soIvent removed.
The residue was collected with 20 ml of water and 0.5 ml
of concentrated HCl, the aqueous solution was extracted with
ethyl acetate ~3x30 ml) and the organic phase was dried with
anhydrous Na2SO4.
;~ The solvent was removed in vacuum and the solid residue,
crystallized from-benzene (10 ml), yielded 1 gram of 1-phenyl-3-
:
-23-.
,~ ~
(1- hydroxy-~-methyl-mercapto)-ethyl -1,2,4-triazole~5)-one
(ivory colored solid, m.p. = 102-104C). (M 8173).
EXAMPLE 6
Operating in the same way as described above in Example
5, but starting from 70 g of 1-phenyl-3-acetyl-1,2~4-triazole(5)-
one, 56 g of 1-phenyl-3-(1-hydroxyethyl)-1,2,4-triazole(5)-one
were obtained (m.p. - 14~-150C).
', , .
OEI
CO-CH3 CH-CH3
H ~ NaBH4 HN ~
N/ ~ ~ (M 8262)
C H C6H5
, .
.. ''~ ' .
EXAMPLE 7
To 16 g of the product obtain~d as described in the
preceding Example 6, dissolved in 350 ml of CHC13, 7.6 ml of
SOCl were added dropwise, under stirring.
The solution was stirred at room temperature for 2 hours,
and then poured into 150 ml of water. The chloroformic phase
was separated and dried. After removal of the so~vent, 17 g of 1-
phenyl-3-(1-chloroethyl)-1,2,4-triazole(5)-one were obtained
(m.p. - 15~-160C). (M 8085).
5.5 g of the last-mentioned product thus obtained,
~ dissolved in 150 ml of benzene, were dehydrochlorinated by
; slightly refluxing in the presence of 7.5 g of triethylamine.
Once the reaction was accomplished, 40 ml of water and 10 ml of
concentrated HCl were added to the reaction mixture.
The benzenic phase was separated, washed with water
and dried with anhydrous Na2SO4. The solvent was removed in
vacuum up to a volume reaching 50 ml. By slight cooling, 2 g of
-24-
~ l-phenyl-3-vinyl-1,2,4-triaæole(5)-one were separated (m.p.
.-: . . .
200C). (M 8263).
EXAMPLE R _
Preparation of l-methyl-3-tribromovinyl-1,2,4-triazole
(5)-one and 1-methyl~3-(d -bromo-~ ,~ -dichlorovinyl)-1,2,4-
triazole (5)-one.
CH
3 -HBr
CC12-CH-CH=N-~-CO-NH2~2Br2 -HCl
.
1 n Br Cl Br Br
HN ~\ C~C\ HN ~ C-C
/ N Cl~O = < N Br
O N N
CH 3
~3) - (2)
, . .
~MW= 273) (MW_ 361.7)
3 g (0.0153 moles) of 1-(~,~-dichloroacrylidene)-2-
methyl-semicarbazide (1) were dissolved in 15 ml of glacial
acetic acid, and then 1.6 ml of bromine (0.031 moles) were
slowly added to this solution. The mixture was then heated (with
slight reflux) for 30 minutes, and then it was cooled and 150 ml
of H20 were added. It was then extracted with ethyl acetate
(50 ml two times). ~he ethyl acetate solution was washed with
50 ml of H20 and with a saturated solution of NaHC03 (40 ml three
times). Then it was dried with anhydrous Na2S04, filtered, and
the solvent evaporated.
The residue was recovered with 50 ml of 10 % aqueous
NaOH and the whole heated up to inciPient boiling. Thereupon
the mixture was cooled and filtered. The filtrate was acidified
with concentrated HCl. A yellowish solid separated which was
extracted with ethyl acetate (2xSOml).
The organic solution was then washed with water t50 ml~
-25-
.
.
6~
dried with anhydrous Na SO , and the solvent removed. 1.9 y of a
yellowish solid were obtained which crystallized from benzene (30
ml), yielded 1 gram of an almost white crystalline solid (m.p. -
~- 161-163C).
~- This solid consists of a mixture of compouncls (2) and
^~ (3), as evidenced by its mass spectrum in which two molecular
peaks of almost equal intensity are present ~-(2): M~ = 3fil.7,
(3): M~ = 273~. From the data upon elemental analysis, it was
calculated that the mixture is composed of 56 % of compound (3)
- 10 and 44 % of compound (2)
- EXAMPLE g
Preparation of l-methyl-3-(~ dichlorovinyl)-1,2,4-
` triazole(5)-one:
HN CH~CCl
CH3 ~ r / ~ 2
CCl -CH-CH=N-N-CO-NH ~ Br ~ ~ /
2 2 2 O N (M 8310)~
CH
~1) (2,
~20
-~ 9.7 g (0.0494 moles) of 1-(~ ,~ -dichloroacrylidene)-2-
methyl-semicarbazide (1) were dissolved in 50 ml of glacial acid.
The solution was slightly refluxed while 2.8 ml (0.054 moles) of
.~
; ~ bromine were very slowly added dropwise. On completion of the
dropwise addition, the solution was alIowed to cool down spon-
taneously.
The ac:etic acid solution was slowly added dropwise to a
suspension of 120 g of NaHCO3 in 300 ml of H2O. Once the effer-
vescence had subsided, 250 ml of ethyl acetate were added and the
whole was stirred.
The organic phase was separated, dried with anhydrous
Na2SO4 and the solvent evaporated. When the volume had been
'
-26-
._
.
reduced to 40 ml, thé evaporation was interrupted and the solu-
tion wa.s cooled down to about 0C. The yellowish precipitate
. was filtered on a porous diaphgram.
.` 2 grams of l~methyl-3-(~ ,~ -dichlorovinyl)-1,2,4-
triazole (5)-one (2~ were obtained (m.p. - 215-216C after re-
crystallization from ethyl acetate).
EXAMPLES 10 - 11
Starting from the appropriate l-(polyhaloacrylidene)-2-
- methyl-semicarbazide and proceeding as described above in Example
.; 10 9, the following 1,2,4-triazole-~5)-ones were prepared:
~ methyl-3-(~ -dibromovinyl )-1,2,4-triazol-(5)-
,! ~ ' one
: H ~ CH=CBr2
N \\
/j< / N (M 8307)
''' O
. H3
-- l-methyl-3-(tribomovinyl)-1,2,4-triazol-~5)-one
:'
Br .
. \ C-CBr
-\< 2
. ~ ~'\ N
O \N / (M 8088)
~3
EXAMPLE 12
.
Preparation of l-methyl-3~ dichlorovinyl)-1.,2,4-
triazol-(5)-one by using ferric chloride:
~ 30
-27-
~ 63l9'^~
~. `.
CH H
¦ 3 \ CH=CCl
C12 C=CH-CH=N-N~CO-NH2-~ 2FeCl ~ N - ~ 2
O / ~ 2FeCl
- N 2
¦ ~ 2HCl
CH
(1) ~2)
A solution of 49 g ~0.18 moles) of hexahydrated ferric
chloride ~FeC13.6H2O), in 100 ml oE water, was added to a
solution of 17.5 g ~0.089 moles) of 1-(~ ,~ -dichloroacrylidene)-
2-methyl-semicarbazide ~1) in acetic acid (50 ml). The resulting
solution was heated at reflux temperature for 3 1/2 hours, and then
left to cool spontaneously following which it was additioned with
150 ml of water. The solution was then cooled at about 0C
(water and ice bath).
12 g of 1-methyl-3-(~ ,~ -dichlorovinyl)-1,2,~-triazole-
5- one (2) precipitated (m.p. - 215-216C, crystallized from
ethyl acetate).
EXAMPLE 13
;20 - Preparation of l-methyl-3-(~ ,~ -dimethylvinyl~-1,2,4-
triazol-5-one.
A H3C\ 3
C-CH-CHo ~H2N-N-CO-NH ~ FeC13 _ _
H C
(1) (2)
CH
H CH=C /
\
CH
- I
CH
(3)
-2~
,:
. .
To a solution of 10.6 g (0.119 moles) of 2-methyl-semi-
carbazide (2) in acetic acid (100 ml), 10 g (0.119 moles) of
-dimethyl-acrolein (1) were added dropwise. I'he reaction
mixture was stirred at 50C for 15 minutes, and then a solution
of 64.2 g (0`.237 moles) of FeC13.6H2O in 60 ml of water was added
to it. The whole was stirred at 75C for 3 hours, and then it was
poured into water ~400 ml) and extracted with ethyl acetate
(2x150 ml). The organic phase was separated, washed with water
and with a saturated solution of ~aHCO3, and dried with anhydrous
; 10 Na2SO4,
By removing the solvent, 4 g of 1-methyl-3-(~ , ~-dime-
thylvinyl)-1,2,4-triazol-5-one (3) were obtained tm.p. - 144-
146C).
EXAMPLE_14
Preparation of l-methyl-3-(~-chloro- ~-methoxyvinyl)-
1,2,4-triazol-5-one.
' '
:
Cl
~ CH-C H Cl
N Cl \~H-C
/ ~ CH OH~KOH ~ / N ~ 3
O N 3 O N IKcl~H2o
CH
3 CH
(1) (2)
Into a round-bottomed flask fitted with a reflux con-
denser, 6.8 g ~0.035 moles) of 1-methyl-3-(~ ,~ -dichlorovinyl)-
1,2,-4-triazol-5-one (1), 50 ml of methanol, and 8 g of KOH were
introduced. The reaction mixture was stirred at reflux
temperature for 5 hours, then Poured into water (150 ml) and
concentrated HCl ~20 ml) and extracted with ethyl acetate
-29-
.
.:
6~
, . , ~
(3xlO0 ml). The organic phase was dried with anhydrous Na SO
and the solvent removed.
3 g of 1-methyl-3-(~-chloro-~ -methoxyvinyl~-1,2,4-
triazol-5-one t2) were obtained (m.p. - 198-199C).
EXAMPLE 15
Preparation of l-methyl-3-(2-chloro-1-cyclohexenyl)-
1,2,4-triazol-5-on~:
H3 /r--~
CH-N-N-CO-NH2 H ~ Cl
Cl ~ FeCl --~
N
(1) CH3
: '
. ' ' .
To a solution of 27 g ~0.1 moles) of FeC13.6H2O in 30 ml
o~ water, 50 ml of acetic acid were added. The resulting solution
was stirred at 100C while a solution of 10.8 g ~O.OS moles) of
the semicarbazone (1) in 50 ml of acetic acid was added dropwise
20 in 2 hours. The heating was maintained for one additional hour,
then the solution was cooled, additioned with 300 ml of water,
and extracted with chloroform (2x200 ml). The chloroformic
extract was separated, washed with a saturated solution of NaHCO3
and dried with anhydrous Na2SO4. By removing the solvent 4.5 g
of an oil were obtained. The oil le$t to stand solidi$ied, and
the solid raw substance upon washing with diethyl ether yielded
4 g of 1-methyl-3-~2-chloro-1-cyclohexenyl)-1,2,4-triazol-5-one
(3) (m.p. - 183-185C). Elemental analysis: Cl theoretical,
16.60%, found, 16.76%.
EXAMPLE 16
Preparation of 0,0-diethyl-0-(1-methyl-3-tribromovinyl-
5-triazolyl)-thiophosphate:
-30-
v~
., ` ,' .
`~ Br Br S OC H
~ / 2 5 -NaCl
N ~ C=C ~ Cl-P
-~ ~\ / Br ~ C2H5
NaO N
CH3
(1) (2)
~ Ir Br
P _ _ O _ /Y - C-C Br
C H / \
- C~3
(3)
'
3.82 g (0.01 moles) of 1-methyl~3~tribromovinyl-5-
hydroxy-1,2,4-triazole (1) (sodium salt) were dissolved in 100 ml
of acetone. To this solution were added 1~6 ml (0.01 moles) of
0,0-diethyl-chlorothiophosphate t2)~ The solution was then
heated to 55-60C for 2 hours. Thereupon the acetone was
evaporated and the residue was collected with 100 ml of diethyl
ether and 50 ml of H2O. The whole was then stirred. The
organic phase was separeted, dried with anhydrous Na2SO4 and the
solvent evaporated. Thereby were ohtained 4.7 g of a yellow oil,
which was purified by chromatography on silica gel, using benzene
as an eluent: yield 3.5 g of 0,0-diethyl-0-(1-methyl-3-
tribromovinyl-5-triazolyl)-thiophosphate (3): (white solid m~p.
=45-50C).
In a similar way the other 0,0-diethyl-0-triazolyl-
thiophosphates reported in TABLE 2 were prepared.
EXAMPLE 17
By operating as described in Example 16, but starting
- from l-methyl-3~ -dichlorovinyl) 5-hydroxy-1,2,4-triazole
(sodium salt) and from 0,0-dimethyl-chlorothiophosphate, the
-31-
63
~;
; 0,0-dimethyl-thiophosphoric ester of 1-methyl-3-(~,~-dichlor-
vinyl)-5-hydroxy-1,2,4-triazole was prepared ~M 8373), (m.p. -
; 102-103C). Elemental analysis: Cl (theor.) : 22.30%; (found):
22.~5%.
XAMPLF. 18
An investigation of the biological activities of the
compounds of the present invention was made as ~ollows:
` 1) Biologlcal activity on Macrosiphum euphorbiae (Aphides):
Potato plants grown in pots were infested with adult
females o aphides and, after several hours, were sprinked
-- with an aqueous dispersion of the products under examination
(see TABI,E 5).
; The percentage of mortality was assessed after 24 hours
after the treatment (untreated plants - 0).
2) Biological activity on Pieris brassicae (Lepidoptera):
Cut-off cauliflower leaves were sprinkled~with an
aqueous clispersion of the products under examination (see
TABLE 5~.
After drying, the leaves were infested with 5-day old
larvae. The percentage of mortality of the larvae (untreated
leaves - 0) was determined after 48 hours from treatment.
3) Blological activity on Leptinotarsa decemlineata (Coleoptera).
Small potato plants grown in pots were infested with
, . .~ 4-day old larvae, and were then sprinkled with an aqueous disper-
i~ sion of the products under examination (see Tables 4 and 5j.
~ The mortality percentage (untreated small plants - 0)
.~ .
was determined after 48 hours from treatment.
4) Biolo~ical activity on Culex p~piens ~Diptera?
; ~ Into glasses containing an aqueous dispersion of the
products under examination (see Tables 4 and 5) there were
introduced mosqulto larvae of third and fourth age.
`~ ~ The mortality percentage of the larvae (glasses
, -
,' ~ ...
~ -32-
. .
.
. i,
containing pure water - 0) was determined after 24 hours from
treatment.
5) Biological activity on adults of Tetranychus urticae tAcari).
Discs of bean leaves were infested with adult acari and
then sprin]cled with an aqueous dispersion of the products under
examination (see Tables 4 and 5).
The mortality percentaye was determined after 24 hours
from treatment ~untreated leaf discs, mortality = 0).
6) Biological activity on Tetranychus urticae ~Acari).
Small discs of bean leaves were inEested with Acari eyys
- and were then sprinkled with an aqueous dispersion of the products
under examination (see Table 5).
The mortality percentage was determined after 6 days
from treatment (untreated leaf discs, mortality - 0).
7) Biological activity on Spodoptera littoralis (Lepidoptera).
Cut tobacco leaves were sprinkled with an aclueous dis-
persion of the products under examination (see Tables 4 and 5).
After drying, the leaves were infested with 5-day old
larvae.
The percentage of mortality of the larvae was determined
after 49 hours from treatment (untreated leaves, mortality = 0).
8) Bioloqical activity on Meloidogyne icognita (Nematoda).
r .___
A 1:1 mixture of filed soil and sand, infested with
newborne larvae and eggs of Nematocla, were treated, by uniform
admixing, with an aqueous dispersion of the products under
examination (see Tahles 4 and 5). The soil was then distributed
into plastic pots, and -after 5 days in each pot there were planted
5 small tomato plants about 20 cm high.
The results were recorded 21 days after the transplant-
ing. The roots of the plants extracted from the soil were observed
in order to ascertain the degree of infestation by counting the
galls that had formed.
-33-
.
: '
The nematocidal activity was expressed as the percentage
reduction of infestation with respect to the witne~s (small plants
transplanted into a non-treated soil, activity - 0).
9) Bioloqical activity on Flil~ia brassicae (Dip~era~,.
Samples of 50il were treated by uniform rnlxing with an
aqueous dispersion of th~ products under examination tsee Tables
4 and 5). The soil was then divided into two pots and in each
of these 4 small radish plants were transplanted. The plants
- .
-, were subsequently infected by putting to the soil 50 Diptera eggs
,' 10 in the middle of the surface of the pots.
The results were recorded 10 days after treabment by
extractin~ the plants from the soil and by counting the number of
, larvae present on the roots and on the surrounding soil.
The insecticidal activity was expressed as percentage of
, reduction of th~ infestation in comparison with the witness plants
(plants transplanted into untreated soil, activity = 0).
10) Biological activity on Blatta orientalis (Ortoptera).
The bottom and walls of qlass crystallizers were treated
,, uniformly with an acetonic solution of the products under exami-
- 20 nation (see Tables 4 and 5). After evaporation of the solvent
,~ into each crystallizer were introduced ten 80-100 days old
,,,~ neanides. The crystallizers were then closed with a metal net
cover. After 24 hours from the start of the treatment, the
r~ insects were transferred to similar untreated crystallizers, and
"~'!'' there were appropriately nourished in conventional manner.
The percentage of martaIity (untreated insects - 0)
;:
~ was determined after 48 hours from the start of the treatment.
' ~
, "
.~ ' .
-34-
.
. . .
