Note: Descriptions are shown in the official language in which they were submitted.
` \\ -- l --
UREA DERIVATIVE USEFUL IN_PRODUCTION OF 4-(2-FLUORO-
4_HALO_5-SUBSTITUTED P_ENYL)URAZOLS
The present invention relates to a novel urea
derivative which is an intermediate in the production of
4-(2-fluoro-4-halo-5-substituted phenyl)urazols bearing a
condensed hexahydropyridazine or hexahydrodiazepine ring
(hereinafter referred to as "the condensed phenylurazol(s)").
This a divisional of application Serial No. 411,694, filed
September 17, 1982.
The said condensed phenylurazols are representable
by the formula:
X ~ N ~ r (C1~)n (I)
wherein X is a chlorine atom or a bromine atom, Y and Z are
each an oxygen atom or a sulfur atom, R is a Cl-C3 alkyl
group, an allyl group or a propargyl group and n is an
integer of 4 or 5.
It is known that some 4-phenylurazols exhibit a
herbicidal activity. For instance, U.S. patent 4,249,934,
Japanese Patent Publication (unexamined) No. 44587/1978,
etc. disclose that 2-(4-chlorophenyl-5,6,7,8-tetrahydro-
lH-[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dione, 2-(4-
chloro-2-fluorophenyl)-5t6~7~8-tetrahydro-lH-[l~2~
triazolo[l,2-a]pyridazine-1,3(2H)-dione, 2-(4-chloro-
phenyl)-lH,5H-[1,2,4]triazolo[1,2-a]~1.2]diazepin-1,3(2H)-
dione, etc. show a herbicidal activity. However, their
2~5
herhicidal e~fect is not al~ays satisfactorv.
It has been found that the condensed phenylurazols
(I) show a strong herbicidal activity against a wide variety
of weeds including Graminaceous weeds, Cyperaceae weeds and
broad-leaved weeds at small doses and do not produce any
material phytotoxicity on various agricultural crops (e.g.
corn, soybean, cotton, wheat). EY.amples of Graminaceous
weeds against which the condensed phenylurazols (I) show a
herbicidal activity are barnyardgrass (Echinochloa
crus-galli), green foxtail (Setaria viridis), large
crabgrass (Digitaria sanguinalis), Johnsongrass (Sorghum
halepense), wild oat (Avena fatua),'black grass ~Alopecurus
myosuroides), goosegrass (Eleusine indica), annual bluegrass
(Poa annua), bermudagrass (Cynodon dactYlon), quackarass
(Agropyron repens), etc. Examples of broad-leaved weeds are
tall morningglory (Ipomoea purpurea), velvetleaf (Abutilon
theophrasti), sicklepod (Cassia obtusifolia), wild sunflower
(Helianthus annus), cocklebur (Xanthium pensylvanicum), wild
mustard (~rassica kaber~, common chickweed (Stellaria
media), common purslane (Portulaca olerecea), jimsonweed
(Datura stramonium), hemp sesbania (Sesbania exaltata), sun
spurge (Euphorbia helioscopia), black nightshade (Solanum
ni~rum), prickly sida (Sida spinosa), common ragweed
(Ambrosia artemisiifolia), smartweed sp. (Polvgonum sp.),
redroot pigweed (Amaranthus retroflexus), bedstraw (Galium
aparine), pineappleweed (Matricaria spp.), birdseye
speedwell (Veronica persica), wild buckwheat (Polyqonum
s
-- 3
convolvulus), beggarticks (Bidens spp.), com~on lambs-
quarters (Chenopodium album), bindweed (Calystegia
japonica), monochoria (~ionochoria vaginalis), Dopatrium
junceum, waterwort (Elatine triandra), false pimpernel
(Lindernia procumbens), toothcup (Rotala indica), arrowhead
(Sagittaria pygmaea), etc. Examples of Cyperaceae weeds are
nutsedge sp. (Cyperus microiria), purple nutsedqe (CYperus
rotundus), yellow nutsedge (Cyperus esculentus), hardstem
bulrush (Scirpus juncoides), nutsedge ~Cyperus serotinus),
water chestnut ( leocharis kuroguwai), slender spikerush
(Eleocharis acicularis~, etc. Accordingly, the condensed
phenylurazols (I) can be used as herbicides applicabl~ to
paddy field as well as agricultural plowed field. They are
also useful as herbicides to be employed for crop field,
orchard, tea garden, mulberry field, rubber plantation,
forest, lawn, pasture, non-agricultural field, etc.
The condensed phenylurazols (I) can be produced by
various procedures, among which typical examples are shown
below:
Procedure A
The condensed phenylurazols of the formula (I)
wherein at least one of Y and Z is an oxygen atom can be
produced by reacting a phenylurazol of the formula:
X ~ IH (II)
wherein X, ~, % and R are each as defined a~ove but at least
one of Y and Z is an oxy~en atom with a dihaloalkane of the
formula:
A-(CH2) -A' (III)
wherein A and A' are each a halogen atom (e.g. chlorine,
bromine) and n is as defined above, usually in an inert
solvent (e.g. dimethylformamide, dimethylsulfoxide,
acetonitrile, ethylene glycol monomethyl ether, tetrahydr~-
furan, diethyl ether) at a temperature of -80 to 200C.
Preferably, the phenyluraæol (II) is previously
metallized, and the metallized phenylurazol is subjected to
reaction with the dihaloalkane (III) The metallization may
be achieved by treatment of the phenylurazol (II) ~ith a
metallizing agent (e.g. sodium alkoxide, sodium hydride,
n-butyl lithium) in an inert solvent (e~g. methanol,
ethanol, diethyl ether, tetrahydrofuran) at a temperature of
-80 to 160C. The thus produced metallized phenylurazol can
be subjected to reaction with the dihaloalkane (III) as
above with or without its isolation from the reaction
mixture.
Procedure B
The condensed phenylurazols of the formula (I)
wherein Z is an oxygen atom and n is an integer of 4 can be
produced by treatment of a urea of the formula:
~2~9265
I` ~'
X ~ N~IC~- ~ (IV)
RO N\ j
R'OOC
wherein R' is a lower alkyl group ~e.g. methyl, ethyl,
n-propyl, isopropyl) and X, Y and R are each as defined
above with a base (e.g. sodium methoxide, sodium hydroxide,
potassium hydroxide) in an inert solvent (e.g. water, ~
toluene, benzene, methanol, ethanol~ at a temperature of 0
to 200C.
Procedure C
The condensed phenylurazols of the formula tI)
wherein Z is an oxygen atom and n is an integer of 4 can be
produced by reacting a urea of the formula:
X ~ NH ~ (V~
wherein X, R and Y are each as defined above with phosgene
in an inert solvent (e.g. toluene, tetrahydrofuran, 1,4-
dioxane) at a temperature of from 0C to the boiling temper-
ature of the solvent. When desired, a base (e.g. triethyl-
amine, pyridine, diethylaniline) may be present in the
reaction system.
Procedure D
The condensed phenylurazols of the formula (I)
wherein Z is a sulfur atom and n is an integer of 4 can be
produced by reacting a urea of the formula:
26Si`
fi
Y
X~ NHCN~\~ (V)
RO' 1~
wherein X, R and Y are each as defined above with carbon
disulfide in an inert solvent (e.g. methanol, ethanol,
tetrahydrofuran~ in the presence of a base such as an alkali
metal hydroxide (e.g. sodium hydroxide, potassium hydroxide)
or a tertiary amine (e.g. pyridine, triethylamine~.
Procedure E
. _
The condensed phenylurazols of the formula (I~
wherein Y and Z are each a sulfur atom can be produced by
reacting the corresponding condensed phenylurazol of the
formula (I) wherein Y and Z are each an oxygen atom with
phosphorus pentasulfide in an inert solvent ~e.g. xylene,
toluene, hexane) at a boiling temperature of the solvent.
The present invention relates to the above urea
derivatives of formula IV, which are novel compounds.
The production of the starting materials is
summarized in the following scheme:
2~
,F /F ,F
X ~ ~ X ~`-NO ~ Xi'~ ` NO
110 HO' RO
(VI) (VII) (VIII)
F Yl /F "F
X ~ NHCN ~ -- X ~ rNCY ~ X ~ NH2
RO /N RO RO
R'OOC (IVJ (X) (IX)
~/
X ~ NHCI ~ X ~ N ~ NH
(V) Z (II)
wherein X, Y, Z, R and Rl are each as defined above.
Namely, the phenol (VI) is selectively nitrated to
the nitrophenol (VII)~ which is subjected to alkylation,
alkenylation or alkynylation. The resultant nitrobenzene
(VIII) is subjected to reduction, and the resulting aniline
(IX) is reacted with phosgene or thiophosgene to give the
isocyanate or isothiocyanate (X), which is reacted with an
N-alkoxycarbonylhexahydropyridazine to give the urea ~IV).
Hydrolysis and decarboxylation of the urea (IV~ give the
urea (V). The above aniline (IX) is reacted with a 2-
alkoxycarbonylhydrazinecarbonyl chloride, followed by
32~S`
- e -
cyclization with a hase to give ~he phenylurazol (II).
Alternatively, the phenylurazol (II) can be produced by
reacting the isocyanate or isothiocyanate (X) with an
alkoxycarbonylhydrazine, follo~ed by cyclization with a
base.
Explaining the above conversions more in detail,
the nitration of the phenol (VI) to the nitrophenol (VII)
may be accomplished by application of a per se conven'ional
nitration procedure to the former. Usually, however, the
indirect nitration which consists of the following three
steps is favorable in achievement of the selective nitration
at the desired position:
J F F
x4 7 x~
HO (VI)H3COCO (XI)
/F /F
~- X-~ ~N02 ~ x~_NO2
H3COCOIXII) HO (VII)
wherein X is as defined above. Thus, the phenol (VI)
(Finger et al.: J.Am.Chem.Soc., 81, 94 (1959)) is converted
into its alkali metal salt by treatment with an aqueous
solution of an alkali metal hydroxide (e.g. sodium
hydroxide, potassium hydroxide), and the resulting salt is
reacted with an alkyl haloformate such as methyl chloro-
. ,:
~'
formate in water at a temperature of 0 to lO~C. The thusprepared carbonic estcr ~XI) is nitrated with a mixture of
conc. sulfuric acid and conc. nitric acid at room temper-
ature. Then, the nitrobenzene (XII) thus obtained is hydro-
lyzed with an aqueous alkaline solution such as an aqueous
sodium hydroxide solution at a temperature of 40 to 80C to
give the nitrophenol (VII~.
The alkylation, alkenylation or alky~ylation for
conversion of the nitrophenol (VII) into the nitrobenzene
(VIII) may be carried out by tre~tment of the former with an
alkali metal carbonate (e.g. potassiumm carbonate), an
alkali metal hydride (e.g. sodium hydride) or an alkali
metal alkoxide (e.g~ sodium methoxide) and reacting the
resultant alkali metal salt with a halide of the formula:
R-Q wherein Q is a halogen atom le.g. chlorine, bromine,
iodine) and R is as defined above in a polar solvent te.g.
water, dimethylformamide, acetonitrile, acetone, dimethyl-
sulfoxide), usually at a temperature of lO to 200C,
preferably of 30 to 100C. The use of a phase transfer
catalyst such as tetrabutylammonium bromide is favorable for
smooth accomplishment of the reaction.
Reduction of the nitrobenzene (VIII) to the
aniline (IX) may be achieved in various procedures. ~1hen,
for instance, R in the compound (VIII) is Cl-C4 alkyl, there
may be adopted a per se conventional reduction procedure for
converting a nitro group into an amino group wherein a
reducing agent such as sodium sulfide or iron powder or
i5
-- 10 --
catalytic reduction is employed. One of typical procedures
comprises introduc~ion of a 3 molar amount of hydrogen into
a reaction system comprising one molar amount of the
compound (VIII) and a 1/10 to 1/100 molar amount of platinum
dioxide at room temperature under atmospheric pressure.
Another typical procedure comprises admi~:ing an acetic acid
solution containing one molar amount of the compound (VIII)
with a 5 ~ acetic acid soluticn containing a 2.5 to 5.0
molar amount of iron powder such as reductive iron or
electrolytic iron and effecting the reaction at a temperture
of 80 to 100C. When R in the compound (VIII) is propargyl
or allyl, there may he adopted reduction with iron powder.
For instance, an acetic acid solution containing one molar
amount of the compound ~VIII) may be admixed with a 5 %
acetic acid solution containing a 2.5 to 5.0 molar amount of
iron powder such as reductive iron or electrolytic iron at a
temperature of 80 to 120C~ preferably of 90 to 110C, for a
period of 0.5 to 5 hours.
The aniline ~IX) is converted into the isocyanate
or isothiocyanate (X) by reacting the former with phosgene
or thiophosgene in an inert solvent (e.g. toluene, benzene,
ethyl acetate, tetrahydrofuran, 1,4-dioxane).
The isocyanate or isothiocyanate (X) can be
converted into the urea (IV) by reacting the former with an
N-alkoxvcarbonylhexahydropyridazine in an inert solvent
(e.g. benzene, toluene, hexane, tetrahydrofuran), preferably
in the presence of an organic base (e.g. pyridine, triethyl-
~Z~32~
11 --
amine), at a temperature from room temperature (ca. 20C) tothe boiling temperature of the solvent.
Hydrolysis and decarboxylation of the urea (IV) by
treatment Wit]l an aaueous alkaline solution at a temperature
of O to lOO~C affords the urea (V).
Alternatively, the phenvlurazol (II) can be
produced by reacting the isocyanate or isothiocyanate (X)
with an alkoxycarbonylhydrazine or alkoxythiocarbonyl-
hydrazine in an inert solvent (e.g. toluene, chloroform,
tetrahydrofuran) at a temperature of 0 to 100C, followed by
treatment of the resultant semicarbazide of the formula:
F Y
X~NE~CNHNHCOR" ( XI I I
RO
wherein ~" is an alkyl group and X, Y, Z and R are each as
defined above with an aqueous alkaline solution such as
potassium hydroxide solution and then with a mineral acid
(e.g. hydrochloric acid, sulfuric acid).
The above obtained aniline (IX) can be converted
into the semicarbazide (XIII) by reacting the former ~ith a
2-alkoxycarbonylhydrazinecarbonyl chloride in an inert
solvent (e.g. benzene, toluene, diethyl ether, tetrahydro-
furan, dioxane) at the boiling temperature of the solvent.
The above produced condensed phenylurazols (I) and
their intermediates are, when desired, purified by a per se
conventional procedure such as recrystallization or column
chroma~ography.
,, .
~2~ 6S
- 12 ~
Practical and presently preferred embodiments for
production of the c~ndensed phenylurazols (I) are shown in
the following Exc~mples.
Example 1
To a solution of metallic sodium (0.7 g) in
methanol (40 ml), 4-(4-chloro-2-fluoro~5-methoxy)urazol
(3.87 g) was added, and the resultant mixture was concen-
trated under reduced pressure. A solution of 1,4-di~romo-
butane (3.5 g) in dimethylformamide (40 ml) was added
thereto. The resulting mixture was stirred at 100 to 110C
for 4 hours. After allowed to cool to room temperature,
water was added to the mixture r whiich was then extracted
with ether. The ether layer was washed with water, dried
and concentrated to give crystals. The crystals were washed
with ether to give 1.26 g of 2-~4-chloro-2-fluoro-5-methoxy-
phenyl)-5,6,7,8-tetrahydro-lH-[1,2,4]triazolo[l,2-a]-
pyridazine-1,3(2H)-dione (Compound No. 1) as colorless
crystals- M.P., 131 - 132C. IR vmax (cm ): 1770, 1720.
NMR ~ (ppm): 1.9 (4H, m), 3.6 (4H, mj, 3.85 (3H, s), 6.85
(lH, d, J=6H~), 7.3 ~lH, d, J=lOHz).
Example 2
To a solution of metallic sodium (0.46 g) in
methanol (20 ml), 2-(4-chloro-2-fluoro-5-methoxyphenyl)-
urazol (2.6 g) was added, and the resultant mixture was
concentrated under reduced pressure. The residue was
dissolved in dimethylformamide (20 ml), 1,5-di~romopentane
(2.3 q) was added thereto, and the resulting mixture was
' ' '
2~S
stirred at 100 to 120C for 4 hours. ~.fter allowed to cool,
water was added to the mixture, which was then extracted
with ethyl acetate. The extract was washed with a saturated
sodium chloride solution, dried over anhydrous masnesium
sulfate and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography and
recrystallized from methanol to give 0.42 g of 2-(4-chloro-
2-fluoro-5-methoxyphenyl)-lH,5H-[1,2,4]triazolo[1,2-a]-
[1,2]diazepine-1,3(2H)-dione (Compound No. 3). M.P., 121.5
- 123C. IR vmax (cm ): 1750, 1680. NMR ~ (ppm): 1.8
(6H, m), 3.9 (3H, s).
Example 3
Ethyl 2-[(4-chloro-2-fluoro-5-(1-methylethoxy)-
phenyl1aminothioxomethyl]-3,4,5,6-tetrahydro-1(2H)-
pyridazinecarboxylate (0.66 g) was dissolved in toluene (20
ml), and several drops o~ sodium methoxide were added
thereto, followed by heating under reflux ~or 3 hours.
Water was added to the resultant mixture, which was then
extracted with toluene. The extract was washed with a
saturated sodium chloride solution, dried and concentrated
to give 0.3 g of 2-14-chloro-2-fluoro-5-(1-methylethoxy)-
phenyl]-5,6,7,8-tetrahydro-lH-[1,2,4]triazolo[1,2-a]-
pyridazine-3-thioxo-1(2H)-one (Compound No. 15). nD
1-5720- IR vmaX (cm ): 1740, lq90, 1250. NMR ~ (ppm)
1.4 (6H, d), 2.0 (4H, m), 3.65 (2H, m), 4.0 (2H, m), 4.45
(lH, m), 6.9 (1~1, d), 7.25 (lH, d).
Example 4
s
~ -(4-Rromo-5-ethoxy-2-fluorophenyl)-lTI,5H-[1.2.4]-
triazolo[1.2-a][1.21diazepine-1,3(2ll)-dione (0.63 g) was
dissolved in xylene (10 ml), and phosphorus pentasulfide
(0.46 g) was added thereto, followed by heating under reflux
for 8 hours. The reaction mixture was filtered to eliminate
insoluble materials, and the filtrate was concentrated under
reduced pressure. The residue was crystallized and washed
with methanol to give 0.65 g of 2-(4-bromo-5-ethoxy-2-
fluorophenyl)-lH,5H-[1,2,4]triazolo[1,2-a][1,2]diazepine-
1,3(2H)-dithione (Compound No. 9). M.P., 173.5 - 174.5C.
IR vmax (cm ): 1290. NMR ~ (ppm): 1.45 (3H, t), 1.9 (6H,
m), 4.07 (2H, q).
Some additional examples of the condensed
phenylurazol II3 produced in the same manner as above are
shown in Table 1.
2~;~
- 15 -
Tahle 1
y
~ ~ ~N (CH2)n (I~
RO ~ ~
¦Nompound X Y IZ n ¦ R I Physical property ¦
1 I C1¦ O ¦ 4-CH3 ¦ M.P. 131-132C
2 ¦ Cl~ S I 4-CH3 ' M.P. 146-147C
3 j C11 O ' 5 -CH3 i M.P. 121.5-123C
4 ¦ Cl¦ S j S 5 CH3 M.P. 229-231C
I Br¦ O O 4 3 M.P. 162.5-164.5C
6 j C11 O i 4 ~j -CH2CH3 I M.P. 116-117C
7 ¦ Brl i 4-CH2CH3 , M.P. 141-143C
8 ¦ Brl O ~ O S -CH2CH3 1 M P. 56-58C
g ~ Br SS 5-CH2C~3 ¦ M.P. 17305-174.5C
10j C1 O, O 4 -CH2CH2CH3I M.P. 97.5-99C
11I C1 SS 4 -CH2CH2CH3I M.P. 181.5-182.5C ¦
12¦ Cl OO 5 -CH2CH2CH3I nD ' 1-5310
13¦ Br OO 4 -CH2CH2CH3I M.P. 92-93C
14 Cl OO 4 -CH(CH3)2 , M.P. 140-142.5C
lS C1 SO 4 -CH(CH3)2 nD5 1.5720
16 Cl SO 4 -CH2CH=CH2 jM.P. 58-63C
, 17 Br OO 4-CH2CH=CH2 M.P. 109-111C
i 18 Cl SO 2C_CH M.P. 148-150C
_
.
,' ~: ' '':
.
. '
- lfi -
Ex~mPle 5
~ solution of 2-fluoro-4-chloro-5-n-propoxyphenyl
isocyanate (1.8 g) in benzene (10 ml) was added to a toluene
solution containing methoxycarbonylhydrazine (0.71 g), and
the resultant mixture was allowed to stand overnight. The
precipitated crystals were collected by filtration and
dissolved in a 4~5 aqueous sodium hydroxide solution (10 ml)
under heating. To the resulting solution, conc. hydro-
chloric acid was added, and the precipitated crystals were
collected by filtration to give 2.6 g of 4-(4-chloro-2-
fluoro-5 n-propoxyphenyl)urazol. M.P., 181 - 182C. IR
vmax (cm ): 3150, 1710, 1680. NMR ~ (ppm): 1.1 (3H, t),
4.0 (3H, q), 7.0 (lH, d), 7.3 (lH, d)
Some examples of the phenylurazol (II) produced in
the same manner as above are shown in Table 2.
- 17 -
able 2
y
~ / ~NH (II)
RO
l Y ¦ Z ~ R ~ Physical property
¦ Cl O -CH3 M.P. 223-224C
Cl S -CH3 Glassy, IR vmax
(cm~l): 316~, 1720
Cl O O -CH2CH2CH3 M.P. 181-182C
Br O O -CH3 M.P. 229-230C
Br O O C 2C~3 M.P. 215-216C
Br O O -CH2CH2CH3 M.P. 189-189.5C
Cl O O 2 M.P. 217-217.5C
Example 6
4-Chloro-2-fluoro-5-(1-methylethoxy)phenyl iso-
thiocyanate (2.8 g~ was added to a solution of 2-ethoxy-
carbony1-3,4,5,6-tetrahydro-(l~I,2H)-pyridazine (1.8 g) and
several drops of triethylamine in toluene (5 ml), and the
resultant mixture was stirred at 25C overnight. Water was
added to the mixture, which was then extracted with toluene.
The toluene layer was washed with water, dried and concen-
trated. The residue was purifiecl by silica gel column
chromatography to give 2 g of ethyl 2-(4-chloro-2-fluoro-
5-(1-methylethoxy)phenylaminothioxomethyl)-3,4,5,6-tetra-
hydro-1(2Hlpyridazine carboxylate. n27 5 1.5534. NMR ~
fppm): 1.3 (3H, t), 1.4 (611, d), 1.8 (4H, m), 4.35 (2H, q),
: ........
265
7.1 ~ , d), 8.0 (1~1, d), 8.45 (1~1, m, -~
Some examples of the urea (IV) produced in the
same manner as above are shown in Table 3.
Table 3
F Y
X ~ NHCN ~ (IV)
RO /N
R'OOC
_ . _ . _ , .,
X Y I R R' ¦ Physical property ¦
Cl 2CH3 n24 0 1 5751
Cl S -CH(CH3)22CH3 nD 1.5534
Cl O -CH2C-CH 2 3 M.P. 135.5-136.5C
Cl S -cH2c--cHCH2CH3 M.P. 105-109C
Br S -CE~2CH2CH32CH3 Glassy
Br S -CH2CH=CH2CH2CH3 M.P. 80-86C
Br O -CH2CH=CH22CH3 M.P. 77-80C
Cl O -CH2CH2CH32CH3 nD 1.5313
Example 7
A solution of ethyl 2-(4-chloro-2-fluoro-5-(1-
methylethoxy)phenylaminothioxomethyl)-3,4,5,6--tetrahydro-
1(2H)pyridazinecarboxylate (0.8 g) in a 5 % ethanolic
potassium hydroxide solution (10 ml) was heated under reflux
for 3 hours. After allowed to cool to room temperature,
ethanol was removed under reduced pressure. The residue was
dissolved in ether, washed with water, dried over anhydrous
magnesium sulfate and concentrated to give 0.3 g of 2-(4-
chloro-2-fluoro 5-(1-methylethoxy)phenylaminothioxomethyl)-
.
: ~ :
2~
- 19 -
3,4,5,6-tetrahydro-(lH,2~1)-pyridazine. ~I.P., 113 - 114.5C.
NMR ~ (pprn): 1.35 (6H, d~, 1.7 (4H, m), 2.95 (2TI, m), 3.45
(lH, t), 4.2 (2~1, m)~ 4.4 (lH, m), 6.95 tl~l, d), 8.25 (lH,
d), 9.85 (lH, m).
Some examples of the urea (V) produced in the same
manner as above are shown in Table 4.
Table 4
F Y
X ~NHC~ ( V )
X Y ~ R I Pjhysical property
.. , , . . ... __ .
Cl S -CH(CH3)2 M-P- 113-114.5C
Cl O -CH2CH2CH3 M.P. 120-122.5C
Cl O -CH2C-CH M.P. 89.5-91.5C
Cl S -CH2C-CH M.P. 96.5-99C
Cl O -CH2CH=CH2 M.P. 91-95C
Br ¦ O -CH2CH=CH2 M.P. 80-86C
Example 8
A solution of 4-chloro-2-fluoro-5-isopropoxy-
aniline (30 g) in toluene (100 ml) was added to a 1 M
phosgene/toluene solution (500 ml) at room temperature (ca.
20C), followed by heating under reflux. The mixture was
concentrated under reduced pressure, and the residue was
distilled to give 26 g of 4~chloro-2-fluoro-5-isopropoxy-
phenyl isocyanate as pale yellow crystals. M.P., 36 - 37C.
B.P., 90 - 91C/3 mmHg.
... ..
'
: . '
:
- 20 -
IR v~ (cm ): 2240.
Some examples of the isocyanate or isothiocyanate
(~) produced in the same manner as above are shown in Table
5.
Table 5
F
X ~ ~NCY (X)
RO
. . . _
X ¦Y ¦ R ¦ Physical property
Cl IO CH3~ P- ~2 - 44.5C
Cl iO 3 7 I M.P. 43 - 44C
Cl i O iso-C3H7- I M.P. 36 - 37C
Br 1 C2H5- ¦ M.P. 35 - 36.5C
Cl ,O I CH2=CHCH2- ¦ B.P. 107C/3 mmHg; nD 1.5481
Cl IO CH-CCH2- M.P. 61.5 - 62.5C
Cl I S CH3- M.P. 79-80C
Cl S I C~l-CCH2- M P. 105-109C
Cl S ~ CH2=CEICH2- nD 1.6228
Br S CH-CCE~- M.P. 71-74C
Br ~ _ _ nD 1.6421 _
Example 9
A mixture of 4~chloro-2-fluoro-5-isopropoxy-
nitrobenzene (13.5 g) and platinum dioxide (0.4 g) in
ethanol (300 ml) was subjected to catalytic reduction with
hydrogen at room temperature (ca. 20C) under atmospheric
pressure, whereby a designed amount of hydrogen was
'~ '.
,, :.
6~ii
- 21 ~
absorbed. The resultant mixture was filtered to remove
insoluble materials, and the ~iltrate was concentr~ted. The
residue was subjected to purification by silica yel
chromatography to give 5.6 g of 4-chloro-2-fluoro-5-iso-
propoxyphen~rlaniline. nD 1.5360.
N~R (CDC13) ~ (ppm): 1.3 (6H, d, J=6Hz), 3.7 (2H,
m, J=1.5Hz), 4.35 (lH, q, J=6Hz), 6.45 (lH, d, J=7Hz), 7.1
tlH, d, J=lOHz).
IR vmax (cm ): 3450, 3550.
Example 10
A suspension of electrolytic iron powder (3.5 g)
in a 5 % aqueous acetic acid solution (5 ml) was heated to
90C, and a solution of 4-chloro-2-fluoro-5-(2-propynyloxy)-
nitrobenzene (5.7 g) in acetic acid (40 ml) was dropwise
added thereto at the same temperature. The resultant
mixture was stirred at 90 - 105C for 1 hour and allowed to
cool to room temperature. Water (200 ml) was added thereto.
Insoluble materials were filtered off, and the filtrate was
neutralized, followed by extraction with ethyl acetate. ~he
extract was dried over anhydrous magnesium sulfate and
concentrated. The residue was washed with petroleum ether
and carbon tetrachloride to give 3.6 g of 4-chloro-2-fluoro-
5-(2-propynyloxy)aniline. M.P. 61.0 - 61.5C.
NMR (C~C13) ~ (ppm): 2.5 (lH, t, J=211z), 3.4 -
4.2 (2H, m, J=16Hz), 4.15 (2H, d, J=2~1z), 6.5 (lH, d,
J=8Hz), 6.95 (lH, d, J=lOHz).
IR vmax (cm ): 3460, 3360, 3280, 2100.
~ - 22 -
Some examples of the aniline (IX) produced in the
same rnanner as above are shown in Table 6.
Table 6
F
X ~ NH2 (IX)
X I R ¦ Physical property
! C2H5 nD 5 1.5503 ,
¦ C2 5 n25'0 1 5680
j Cl ¦ 3 7 nD 1.5386
¦ Br ! 3 7 nD j1.5618
Cl , iso-C3H7- nD ' 1.5360
Br ~ iso-C3H7- n25 0 1 5547
Cl ¦ CH2=CHCH2- nD 1-5598
Cl ¦ CH-CCE~2- M.P. 61.0 - 61.5C
Cl I CH-C-CEI- M.P. 67.0 - 68C
CH3 __ ___
Example 11
To a solution of 2-chloro-4-fluoro-5-nitrophenol
(19.1 g) in acetonitrile (100 ml~, there was added anhydrous
potassium carbonate (8 g). ~fter stirring at room temper-
ature (ca. 20C) for several minutes, isopropyl iodide (25
g) was added thereto, and the resultant mixture was heated
under reflux for 3 hours. After allowed to cool to room
temperature (ca. 20C), water was added thereto, and the
reaction mixture was extracted with ether. The ether
- 23 -
extract was washed with a 5 % aqueous sodium hydroxide
solution and water in order, dried over anhydrous magnesium
sulfate and filtered. The filtrate was concentrated under
reduced pressure, and the residue was recrystallized from
ethanol to give 13.5 g of 4-chloro-2-fluoro-S-isopropoxy-
nitrobenzene. M.P., 61.3 - 62.4C.
NMR (CDC13) ~ (ppm): 1.42 (6H, d, J=7~1z), 4.3 -
4.8 (lH, m), 7.28 (lH, d, J=lOHz), 7.48 (lH, d, J=6Hz).
Some examples of the nitrobenzene (VIII) produced
in the same manner as above are shown in Table 7.
~2~92~
- 24 -
! Table 7
. _
X ~ ~WO2 (VIII)
RO
, . _ _
X ¦ R j Physical property
. ---- _ ,
¦ Cl -CH3 M.P. 67.5 - 69.8C
¦ Br -CH3 M.P. 72.2C
Cl ~ 2CH3 M.P. 47 - 48C
Br 2 3 M.P. 46 - 46.5C
Cl -CH2CH2CH3 M.P. 46 - 47C
Br -CH2CH2CH3 M.P. 46.8 - 47.4C
Cl -CH¦CH3)2 M.P. 61.3 - 62.4C
Br -CH~CH3)2 M.P. 65.5 - 66.5C
Cl -CH(CH3)CH2CH3 M;P. 59.6 - 60.6C
Cl -CH2CH=CH2 nD 1.5601
Cl -CHCH=CH2 M.P. 41.0 - 41.5C
Cl ~CH2C-CH M.P. 88 - 89C
I Cl -CHC-CH M.P. 87 88~
Example 12
2-Chloro-4-fluorophenol (83.4 g) was added to a
solution of sodium hydroxide (27.7 g) in water (450 ml), and
methyl chloroformate (69.2 g) was dropwise added thereto at
a temperature below 10C. Precipitated crystals were
collected by filtration and washed with water to give methyl
:
- 25 -
(2-chloro-4-fluorophenyl)formate ~134.8 ~ I.P., 69 -
71C.
Methyl (2-chloro-4-fluorophehyl)formate (134.8 g)
obtained above was suspended in conc. sulfuric acid (50 ml).
To the suspension, a mixture of conc. sulfuric acid (SO ml)
and conc. nitric acid (50 ml) was added at about 30C, and
the mixture was stirred at this temperature for l hour. The
reaction mixture was poured into ice water, and precipitated
crystals were collected and washed with water to give methyl
(2-chloro-4-fluoro-5-nitrophenyl)formate (143 g). M.P~, 50
- 55C
The product obtained as above was combined with
sodium hydroxide (27 g) and water (300 ml), and the
resultant mixture was refluxed for 4 hours. Precipitated
insoluble materials were fil~ered using Celite~ and the
filtrate was acidified with conc. hydrochloric acid.
Precipitated crystals were collected by filtration and
washed with water to obtain 76.3 g of 2-chloro-4-fluoro-5-
nitrophenol. M.P., 106 - 107C.
NMR (CDC13, D6-DMSO) ~ (ppm): 7.2~ (lH, d,
J=lOHz), 7.64 (lH, ~, J=6Hz).
IR vmax (cm ): 3370.
Example 13
To a solution of 2-bromo-4-fluorophenol (28 g) in
a solution of sodium hydroxide (7 g) in water (100 ml),
methyl chloroformate was dropwise added thereto at a
temperature below 10C. The produced crystals were
2~5
2G -
collected by filtration and washed with water to give methyl
2-bromo-4-fluorophenylformate (41 a). M.P., ~0.7C.
The above product was suspended in conc. sulfuric
acid (13 ml), a mixture of conc. sulfuric acid (13 ml) and
conc. nitric acid (13 ml) was dropwise added thereto at
about 30C, and the resultant mixture of stirred for 30
minutes. The reaction mixture was poured into ice water.
The produced crystals were collected by filtration and
washed with water to give methyl 2-bromo-4-fluoro-5-nitro-
formate 138.3 g) as yellow crystals. M.P., 63.5 - 64.5C.
The thus obtained product was admixed with sodium
hydro~ide (6.2 g) and water (100 ml)' and heated under reflux
for 3 hours. The insoluble materials were eliminated by
filtration~ and the filtrate was acidified with hydrochloric
acid. The precipitated crystals were collected by filtr-
ation and washed with water to give 25 g of 2-bromo-~-
fluoro-5-nitrophenol. M.P., 126 - 127C.
NMR (CDC13, D6-DMSO) ~ (ppm): 7.~2 (lH, d,
J=lOHz), 7.65 (lH, d, J=6Hz).
IR ~ i (cm ): 3~50.
max
In the practical usage of the condensed phenyl-
urazols (I), they may be applied as such or in any composi-
tion form such as emulsifiable concentrates, wettable
powders, suspensions, granules or fine granules.
The concentration of the active ingredient in such
composition form is usually within a range of 0.1 to 90 % by
weight, preferably of 1 to 80 % by weight.
- 27 -
For formulation of those compositions, a solid or
liquid carrier or diluent may be used. ~s the solid carrier
or diluent, there may be employed mineral powders (e.g.
kaolin clay, bentonite, talc, diatomaceous earth, Sericite,
synthetic hydrated silicon dioxide)~ As the liquid carrier
or diluent, there may be employed aromatic hydrocarhons
(e.g. xylene, methylnaphthalene), ketones (e.g. cyclohexa-
none, isophorone~, chlorobenzene, dimethylformamide, cello-
solve, ethylene glycol, water, etc~
A surface active agent used for emulsification,
dispersion or spreading may be any of the non-ionic,
anionic, cationic and amphoteric type of agents. Examples
of the surface active agent include polyoxyethylene alkyl
ethers, polyoxyethylene alkylaryl ethers, polyoxyethylene
fatty acid esters, sorbitan fatty acid esters, polyoxy-
ethylene sorbitan fatty acid esters, oxyethyleneoxypropylene
polymers, polyoxyethylene alkyl phosphates, fatty acid
salts, alkyl sulfates, alkyl sulfonates, alkylaryl sulfo-
nates, alkyl phosphates, polyoxyethylene alkyl sulfates,
quaternary ammonium salts and the like. If necessary,
gelatin, casein, sodium alginate, starch, agar, polyvinyl
alcohol, ligninsulfonates, isopropyl ac d phosphate,
alginates or the like may be used as an auxiliary agent.
Practical embodiments of the herbicidal composi-
tion according to the invention are illustratively shown in
the following examples wherein part(s) and % are by weight.
The compound number of the active ingredient corresponds to
2~5
the one in Table 1.
Formulation Exam~le 1
Eighty parts of Compound NoO 10, 3 parts of alkyl-
sulfate, 2 parts of ligninsulfonate and 15 parts of
synthetic hydrated silicon dioxide are well mixed while
being powdered to obtain a wettable powder.
Formulation Example 2
Twenty parts of Compound No. 14, 10 parts of
polyoxyethylene alkylaryl ether, 50 parts of cyclohexanone
and 20 parts of xylene are well mixed while being powdered
to obtain an emulsifiable concentrate.
Formulation Example 3
0.1 Part of Compound No. 10, 1 part of synthetic
hydrated silicon dioxide, 35 parts of bentonite and 63.9
parts of kaolin clay are well mixed while being powdered.
The mixture is then kneaded with water, granulated and dried
to obtain granules.
Formulation Example 4
Three parts of Compound No. 1, 0.3 part of
isopropyl acid phosphate, 66.7 parts of kaolin clay and 30
parts of talc are well mixed while being powdered to obtain
a dust.
Formulation Example 5
Eighty parts of Compound No. 3, 5 parts of
polyoxyethylene alkylaryl ether and 15 parts of synthetic
hydrated silicon dioxide are well mixed while being powdered
to obtain a wettable powder.
. .
:.
.~ ,
2iE;S
- 29 -
Formulation E~am~le G
Ten par~s of Compound No. 10, 7 parts of polyoxy-
ethylene alkylaryl ether, 3 parts of alkylarylsulfate and 80
parts of cyclohexanone are well mixed while being powdered
to obtain an emulsifiable concentrate.
Formulation Example 7
One part of Compound No. 9, 1 part of synthetic
hydrated silicon dioxide, 5 parts of ligninsulfonate and 93
parts of kaolin clay are well mixed while being powdered.
The mixture is then kneaded with water, granulated and dried
to obtain granules.
Formulation ~xample 8
Three parts of Compound No. 3, 0.5 part of
isopropyl acid phosphate, 66~5 parts of kaolin clay and 30
parts of talc are well mixed while being powdered to obtain
a dust.
Formulation Example 9
Twenty parts of Compound No. 9 is mixed with 60
parts of an aqueous solution containing 3 ~ polyoxyethylene
sorbitan monooleate and pulverized until the particle size
of the active ingredient becomes less than 3 microns.
Twenty parts of an aqueous solution containing 3 ~ of sodium
alginate as a dispersing agent are incorporated therein to
obtain a suspension.
The dosage rate of the condensed phenylurazols (I)
may vary depending upon the application mode such as pre-
emergence treatment or post-emergence treatment, etc.
~L9Z~S
- 30 -
Generally, h~wever, the dosage rate is from 0.1 to 50 arams,
preferably from 0.2 to 30 grams, of the active ingredient
per are. sesides, the condensed phenylurazols (I) of the
invention may be used together with other herbicides to
improve their activity as herbicides, and in some cases, a
synergistic effect can be expected.
The application of the condensed phenylurazols (I)
as herbicides will be illustratively shown in the following
Examples wherein the phytotoxicity to crop plants and the
herbicidal activity on weeds were evaluated as follows: the
aerial parts of the test plants were cut off and weighed
(fresh weight); the percentage of the fresh weight of the
treated plant to that of the untreated plant was calculated
with the latter fresh weight taken as 100; and the
phytotoxicity and the herbicidal activity were evaluated by
the standard given in the table below.
Rating Fresh weight
value (percentage to untreated plot) (~)
Herbicidal activity Phytotoxicity
. ._ . __
0 61 - 100
141 - 60 90 - 99
221 - 40 80 - 89
311 - 20 60 - 79
4 1 - 10 40 - 59
0 0 - 39
The following compounds were used in the Examples
for comparison:
2~;
Compound
No.Structure Remarks
.
~a) O U.S. patent
il 4,249,934
C 1 ~N~N~
Il
o
(b) O Japanese Patent
F ~ Publn. (un-
~ / N examined) No.
C1 ~ 1~ 44587/78
(c) O j U.S. patent
O 4,249,934
(d) O Commercially
/ 2 5 1 1 available
CCH2Cl herbicide
,-N \ known as
0CH3 "Alachlor"
C2H5
(e) Cl Commercially
L available
N~A~N herbicide
I ll known as
(CE~3)2HCHN ~N~-~NHC2H5 "Atrazine"
(f) I Commercially
~ available
NC~/ ~OH herbicide
known as
~I "Ioxynil"
- 32 -
Compound
No. Structure Remarks
(g),Cl OC~13 Commercially
~ ~r< available
Cl~ \~~ \~NO2 herbicide
~==/ \~=~ known as "Chlor-
methoxynil"
Test Example 1
Plastic beakers (diameter, 10 cm; height, 10 cm)
were filled with upland field soil, and the seeds of
barnyardgrass, wild oat, tall morningglory and velvetleaf
and the seeds of soyben, cotton and corn were separately
sowed in the beakers. A designed amoun-t of the test
compound formulated into an emusifiable concentrate
according to Formulation Example 2 or 6 and dispersed in
water was sprayed over the top by means of a small hand
sprayer at a spray volume of 5 liters per are. After the
spraying, the test plants were grown for 20 days in tne
greenhouse, and herbicidal activity and phytotoxicity were
examined. The results are shown in Table 8.
, .
'''-
-- 3 3
3o
_ _ _ ~ .P w ~ ~ ro
O ~ ~ ~ o O
. _~ . I > 3
DJ
~ ~n ~ Ul ~ U~ ~ ut ~ ~n ~ ~n ~ u~ ~ ~n ~ u~ Ul ~ ~n ~ ~n ~n ~ Ul ~ ~n ~ ~ ~ O ~D
u~ Ul ~n U~Ul Ul ~n i~ c~
~3~
: ~.
~ W o S- u~ ~ ~ ~
O ~ i
O 1~ 0 ~~ O O Ul ~ ~ ~n ~ Ul ~ Ul ~ Ul ~n ~n ~ Ul ~n ~,n ~n Ul Ul Ul Ul ~n Ul Ul r~ ~-
. ~
~43~3 pJ
o o ~ ~ o o vl ~n ul U- Ul Ul U~ Ul ~ ~n ~n Ul I .P ~n Ul ~n ~ U~ ~n ~n ~ ul ul ~ 3 ~- O
~4 ~,
_ _._ ._~
__ O _
O I ~ I O I I I ) I I I ~ I 1-~0 1 001~ OOI~ 1 '
. O
O I W I 1~ 1 I I I I I I I I O 1~ 0 1 1 1 1 1_ 1 1 1 1 1 1 1 1 r X
__ _ . . _ .. _ _ _ I ~<
I I IJ I O I I I I I I 1 1_ 1 _ ~
s
- 3~ -
Test ExamDle 2
In plastic pots (diameter, 10 cm; height, 10 cm)
filled with upland field soil, the tubers of purple nutsedge
were transpl~nted and culti~ated in a greenhouse for ~
wee~s. Separately, the seeds of barnyardgrass, wild oat,
wild mustard and vèlvetleaf were sowed in the similar pots
and grown for 2 wee~s in the greenhouse. A designed amount
of the test compound formulated in an emulsifiable
concentrate according to Formulation~Example 2 or 6 and
dispersed in ~ater with a spreading agent was sprayed to the
foliage of the test plants by means of a small hand sprayer
at a sprav volume of 5 liters per are. ~fter the spraying,
the test plants were further grown for 3 weeks in the
greenhouse, and the herbicidal activity was examined. The
results are shown in Table 9.
Among the test plants, purple nutsedge was further
grown for 2 weeks in the greenhouse, and the number of
revived sprouts in the treated plot was compared with that
in the untreated plot. Evaluation was made on the following
criteria: A, no revival; B, 1 to 10 % revival; C, 11 - SO %
revival; D, more than 51 % revival. The results are also
shown in Table 9.
6~
.` . . ~ . _ _ .
,
h Q.~ ~3 1 1 1 ~ I I I ~ I fl I I ~ I ~¢ I m
h ~ ~ ~J
P~ O P~ ~
_~ . ~
~ r~ ~n m ~n In I m In u~ In ~n I m In I m In In I m In ~n ~n n In In m In m ~r ~ In r - ~r
~ ~, _~
~n ~r In ~n I In u~ u~ In r~ I In In I m In ~ r r~) m In In In In m In ~ o r~ o
~a ~ -- . .
.~1 3 ~n ~ In r~ r ~ r~ n I I In In ~ I ~r ~r r~l ~ r- ~r ~ In m ~ o o ~ o o
~C ~ _
m ~ ~ n I In m ~ i Ln I I In m ~ I u~ ~r ~ m r~ ~ m u~ u~ o o ~ o o
.. 0,1 ~ .
a) .c a.) ~ 'n 'n u~ u~ 'n m 'n m u~ m r~l r~l
a~ 0 3 ~ ~ In _~ ~n ~ o n ~1 ~n In ~ o In ~ o m In ~ o m n ,~ In ~ In ~ ~ n ,; In ~ In ~; In
R C~
E~ ~ ~
n. O ~ ~r ~D r c~ ~ _ _
_ . _ _ . _ . . . _ _ _ _ _ _ . _ _ _ _ _ _ . _ _ . _ _ . . . _ _ _ _ _ _ . _ _ _ _ .
~2~
- 36 -
Test Example 3
Plastic trays (35 cm x 25 cm ~ 15 cm) were filled
with upland field soil, and the seeds of tall morningglory,
velvetleaf, prickly sida, jimsonweed, black nightshade,
redroot pigweed, johnsongrass and green foxtail, and the
seeds of cotton and soybean were sowed therein. A designed
amount of the test compound formulated into a wettable
powder according to formulation Example 1 or 5 and dispersed
in water was sprayed over the top by means of a small hand
sprayer at a spray volume of 5 liters per are. After the
spraying, the test plants were grown in a greenhouse for 20
days, and phytotoxicity and herbicidal activity were
examined. The results are shown in Table 10.
;,, ' ~
'
~ 2
.
~ , , ~ o o C~J o , o
~X -c- _ .
vo ~~ '~'`'I
--C~
x ~ ~
a _
,c~ u~ t oc~looc~
0~o~,
~ ~0 ~ u~
~ ~r~ __
~,~ ~ c~ u~ c~ ~ ~t ~t ~
. .
~u ~ ~ u~ If~ u) It~ O r~ ~1 o o
X ~:~
~ u~ c~t~
:~ ~ u~ ~t U)~t u, o
.. .. I
~ F oo u~ o O ~ o o ~1
o ol ~
L) ~ ~U~U~
c) r ~ c) _~ . .
E~ o 3 t~ ~ ~ u~ v~ o
~ o, __ __
e ~ O o ~a u ~
3~
-
~,
. ,
216~
- 38 -
Test Example 4
Plastic trays (35 cm x 25 cm x 15 cm) were filled
with upland field soil, and the seeds of corn, wheat,
velvetleaf, cocklebur, tall morningglory, common lambs-
quarters, black nightshade, common chickweed and green
foxtail were sowed and grown for 2 to 3 weeks in a green-
house. Every two trays were placed in a frame ~50 cm x 100
cm x 40 cm) and a designed amount of the test compound was
sprayed thereover by means of a small hand sprayer. The
test plants were further grown for 3 weeks in the greenhouse
and herbicidal activity and phytotoxicity were examined.
The results are shown in Table 11. In this treatment, the
test compound was formulated into an emulsifiable concen-
trate according to Formulation Example 2 and applied by
diluting it in water (25 liters) with the addition of a
spreading agaent. At the time of application, the plants
were generally at the 1 to 4 leaf stage and in 1.5 to 20 cm
height.
2~5
'~, _
X ~ r r~) ~'\1 ~r t~l 1~1 O O O
E u ~ .
os: 3 ~rO~rr~J I I ~r~r~
~ X~ u~ llu~
~ ~:~
~ ~ I Q)
~ ~ ~ u~ I I ~n In
o ~r
E-,~O ou~u~o u~
X~ ,n.nu~m u~r~ll
~,~
~nl ~n.n,n~ u~r, ,
O O L ~1 0 ~ 1 i I O O
~1 .CO ~ ~ 1 0011 ..
~1 ~
~ c),c a~ ~ -- ~ ~ ~ ~r)
5~ ~ ~ ) Il
E~ 0 3 ~ ~ ") o o o o
o o o ~ ~ a~
~Q.Z _ .___
~9
6~;i
- 40 -
Test Exa~iple 5
Wagner's pots (1/5000 are) were filled with paddy
field soil and the seeds of annual weeds (e.g. barnyard-
grass, monochoria, broad-leaved weeds) were sowed to 2 to 3
cm depth, and water was poured therein. The tubers or buds
of perennial weeds (e.g. slender spikerush, hardstem
bulrush, arrowhead) were transplanted therein and grown for
5 days. At the time when the germination occured, a
desinged amount of the test compound formulated in an
emulsifiable concentrate according to Formulation Example 2
or 6 was applied to the pots by perfusion. Thereafter, the
test plants were grown for further 4iweeks and herbicidal
activity was examined. The results are shown in Table 12.
2~5
' ~
3~ o~o~r oooo~o~lo
h C) .
~S
h ~1 u~ ~ ~ O ~1 o ~ o _~ o
:~,a
.~ S
~) 'O Q) n G 11~ ~ ~ O ~I r~l ~1 0 ~
~ 11~ __
rl
o ~ ~ ~a u~) ~ 0 (~
,~ o ~ a
~ m ~ 3
5: 'o
S ~ f ~
'!
~1 .
~u~ ~ r oooooo~
_
~0
S ~ ~ Ir) LO U~ U~
a) ~ 1 'a h .... ... .....
U~O~O({) oOoo oOoooooo
3
a~
E~
o
~ ~r ~
O O a~ ~ _ _ _ _.
, _. ___ .._ _ _ _ _
., ~/
" ; - , ~ . , . ~
