CA2005740A1 - Substituted semicarbazone arthropodicides - Google Patents

Substituted semicarbazone arthropodicides

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Publication number
CA2005740A1
CA2005740A1 CA 2005740 CA2005740A CA2005740A1 CA 2005740 A1 CA2005740 A1 CA 2005740A1 CA 2005740 CA2005740 CA 2005740 CA 2005740 A CA2005740 A CA 2005740A CA 2005740 A1 CA2005740 A1 CA 2005740A1
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Canada
Prior art keywords
optionally substituted
ocf2h
alkyl
co2me
ocf3
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
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CA 2005740
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French (fr)
Inventor
John Powell Daub
George Philip Lahm
Bradford Senn Marlin
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EIDP Inc
Original Assignee
EI Du Pont de Nemours and Co
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Filing date
Publication date
Application filed by EI Du Pont de Nemours and Co filed Critical EI Du Pont de Nemours and Co
Publication of CA2005740A1 publication Critical patent/CA2005740A1/en
Abandoned legal-status Critical Current

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Abstract

TITLE
SUBSTITUTED SEMICARBAZONE ARTHROPODICIDES

ABSTRACT OF THE DISCLOSURE

Substituted semicarbazones, including all geometric and stereoisomers thereof, of the following formula, are useful as arthropodicides:
1. A compound of the formula wherein:
Q is , , , , , , , A is (CH2)t, O, S(O)q, NR7, OCH2 or S(O)qCH2, wherein, each carbon individually can be substituted with 1 to 2 substituents selected from 1 to 2 halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C7 alkylcycloalkyl, C2-C4 alkoxycarbonyl, or phenyl optionally substituted with 1 to 3.
substituent independently selected from w;
R1 and R2 are independently R8, halogen, CN, NO2, N3, SCN, OR8, SR8, SOR8, SO2R8, NR8R9, C(O)R8, CO2R8, C(O)NR8Rg~ OC(O)R8, OC02R8, OC(O)NR8R9, NRgC(O)R8, NR9C(O)NR8R9, OSO2R8, NR9SO2R8, or when m is 2, R1 is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O OR CH2CH2O

each of which is optionally substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups, or when n is 2, R2 is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O or CH2CH2O
each of which can be substituted 1 to 4 halogens or 1 to 2 methyl groups; R2 being other than CH3 when R1, R3 and R4 are H and A is CH2;
R3 is H, C1-C6 alkyl, C1-C6 haloalkyl, C4-C6 alkylcycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 cyanoalkyl, C3-C8 alkoxycarbonylalkyl, OR8, S(O)qR8, NR8R9, CN, CO2R8, C(O)R8, C(O)NR8R9, C(S)NR8R9, C(S)R8, C(S)SR8, phenyl optionally substituted with (R10)p or benzyl optionally substituted with 1 to 3 substituents independently selected from W
or R3 is C3-C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3;
R4 is H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 cyanoalkyl, phenyl optionally substituted with (R10)p or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R5 and R6 are independently H, C1-C22 alkyl, C2-C22 alkoxyalkyl, C2-C22 alkylcarbonyl, C2-C22 alkoxycarbonyl, C2-C22 haloalkyl carbonyl, C2-C22 haloalkoxycarbonyl, SR11, CHO, C1-C4 alkylsulfonyl, phenylsulfonyl optionally substituted with 1 to 3 substituents independently selected from W;
C7-C15 phenoxycarbonyl optionally substituted with 1 to 3 substituents selected from W; C7-C15 phenylcarbonyl optionally substituted with 1 to 3 substituents independently selected from W;
C(O)CO2C1 to C4 alkyl, C8-C12 benzyloxycarbonyl optionally substituted with 1 to 3 substituents independently selected from W; or R5 and R6 are independently phenyl optionally substituted with 1 to 3 substituents independently selected from W, or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R7 is H, C1-C4 alkyl or phenyl optionally substituted with W; SR8, SOR8, SO2R8, C(O)R8, CO2R8, C(O)NR8R9, C(S)NR8R9, C(S)R8, C(S)OR8, P(O)(OR8)2, P(S)(OR8)2, P(O)(R3)OR8 or P(O)(R8)SR8; provided that when R7 is other than COR8, C(C))NR8R9 or C(S)NR8R9 then R8 is other than H;
R8 is H, C1-C6 alkyl, C1-C6 haloalkyl, C4-C7 cycloalkylalkyl, C4-C7 halocycloalkylalkyl C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 alkylthioalkyl, C1-C6 nitroalkyl, C2-C6 cyanoalkyl, C3-C8 alkoxycarbonylalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, phenyl optionally substituted with 1 to 3 substituents independently selected from W

or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R9 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or R8 and R9 is optionally taken together as (CH2)4, (CH2)5 or (CH2CH2OCH2CH2);
R10 is R8, halogen, CN, NO2, N3, SCN, OR8, SR8, SOR8, SO2R8, NR8R9, COR8, CO2R8, CONR8R9, SO2NR8R9, OC(O)R8, OCO2R8, OC(O)NR8R9, NR9C(O)R8, NR9C(O)NR8R9, OSO2R8, NR9SO2R8 or when p is 2, R10 is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O, or CH2CH2O each of which is optionally substituted with independently, 1 to 4 halogen atoms or 1 to 2 methyl groups;
R11 is C1-C22 alkyl, C1-C22 haloalkyl, phenyl optionally substituted with 1 to 3 substituents independently selected from W, or R11 is NR12C(O)R13, NR12S(O)aR13, C(O)R13, N12R16, SR14, , or ;

R12 and R16 are independently selected from C1 -C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, C2-C6 cyanoalkyl, C2-C6 alkoxyalkyl, C3-C6 alkoxycarbonylalkyl, C4-C8 dialkylaminocarbonylalkyl, phenyl optionally substituted by 1 to 2 substituents selected from W, benzyl optionally substituted by 1 to 2 substituents selected from W and phenethyl optionally substituted by 1 to 2 substituents selected from W, or R12-R16 is optionally taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2, each ring optionally substituted with 1 to 2 CH3;
R13 is F, C1-c20 alkyl, C1-C6 haloalkyl, C2-C8 dialkylamino, piperidenyl, pyrrol-idenyl, morpholinyl, phenyl optionally sub-stituted with 1 to 3 substituents selected from W, or R13 is C1-C20 alkoxy C1-C6 haloalkoxy or C1-C4 alkoxy substituted with cyano, nitro, C1-C4 alkoxy, C4-C8 alkoxyalkoxy, C1-C2 alkylthio, C2-C3 alkoxycarbonyl, C3-C5 dialkylaminocarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W, or R13 is phenoxy optionally substituted with 1 to 3 substituents selected from W;
R14 and R15 are independently selected from C1-4 alkyl, C2-C4 haloalkyl, phenyl optionally substituted with 1 to 3 substi-tuents independently selected from W or R14 and R15 is optionally taken together as (CH2)2, (CH2)3 or CH2C(CH3)2CH2;
W is halogen, CN, NO2, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio, C1-Cz haloalkylthio, Cl-C2 alkylsulfonyl or C1-C2 haloalkylsulfonyl;
m is 1 to 5;
n is 1 to 4;
t is 0 to 3;
q is 0 to 2;
p is 1 to 3;
a is 0 to 2;
V is O or S;
X is O or S;
Y is O or S; and Z is O or S.

Description

7'~

~I~L~ ~A-8780-~
SU~STITU~ SE~IÇARBAZONE AR~ROPODICIDE~

BACKGROUND OF THE INVENTION
U.S. 4,547,524 discloses benzoyl hydrazone derivatives as insecticides.
WO 8800197 discloses as part of a broader scope substituted semicarbazones derive~ from chromanones and thiochromanones as intermediates used in the preparation of insecticides.
EP-3,913 discloses substituted oenzophenone hydrazones to be useful as insect.icides.
EP-26,040 discloses a broad scope of substituted hydrazones to be useful as insecticides.
~P~254,461 discloses N--substituted hydrazones to be useful as insecticides~
J. Ind. Chem. Soc. 37, pages 99~ to 50 (1960) discloses a compound o~ the lormula:
2 5 CH3 /~

N- NHCNH

but no utility therefor.

S~MMARY OF ~E INvENTION
This invention pertains to compounds of Formula I, including all geometric isomers, stereoisomers, and agronomically and nonagronomically suitable salts :
.

2~)~)57~

thereof, compositions containing them, and their use as agronomic and nonagronomic arthropodicides:

X ~ R, ~ m Q--N--C--N~
R5 ~6 I

wherein:
~ is tR~ )n .

(~?z)n R4 N~
~R2)n N- N-Q-3 Q_4 ' . . :

( R2 ~ n~ ~ R2 ) ~ IJ
Q~5 Q-6 ~ ~z ) n ~ ~ Q~ ~ n~

Q~7 Q-8 A is (CH2)t~ , S(O)q~ NR7, OCH2 or S(o~qcH2, wherein, each car~on individually can be substituted with 1 to 2 substituents : selected from 1 to 2 halogen, Cl-C6 alkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C7 alkylcycloalkyl, C2-C4 alkoxycarbonyl, or phenyl optionally substituted with 1 to 3 substituent independently selected from W;
R1 and R2 are independently R8, halogen, CN, NO2, N3, SCN, OR8, SR8, SOR8, SO2R8, NR8R9, C(O)R8~ C02R8, C(O~NR8Rg~ OC~O)R8, OC02R8, OC(O~NR8Rg, NRgC(O)R~ NRgC(O)NRaR9, OSO2R8, NRgSO2R~, or when m is ~, Rl is optionally taken together to form a 5 or 6 membered fused ring as OCH20, OCH2CH20 OR CH2CH20 :~ .
: , , 7D~

each of which is optionally substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups, or when n is 2, R2 is optionally taken together to form a ~ or 6 membered fused ring as OCH2O, OCH2CH2O or CH2CH2O
each of which can be substituted 1 to 4 halogens or 1 to 2 methyl groups; R2 being other than CH3 when Rl, R3 and R4 are H and A is CH2;
R3 is H, Cl-C6 alkyl, Cl-C6 haloalkyl, C4-C6 alkylcycloalkyl, C2-C6 alkenyl, C2-C6 : haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C~-Cs cyanoalkyl, C3-C8 alkoxycarbonylalkyl, OR8, S~O)qR8~ NR8Rg, CN, CO2R8, C(O)R8, C(O)NR8Rg~ C(S)NR8Rg~ C(S)R8, C(S)SR8, phenyl optionally substituted with (Rlo)p or benzyl optionally substituted with 1 to 3 substituents independently selected ~rom W
or R3 is C3-C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3;
R4 is H, Cl-C6 alkyl, Cl-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2~C6 alkoxyalkyl, C2-C6 cyanoalkyl, phenyl optionally substituted : ~ith (Rlo)p or benzyl optionally substituted with 1 to 3 substituents independently `: selected from W;
R5 and R6 are independently H, Cl-C22 alkyl, C2-C~2 alkoxyalkyl, C2-C22 alkylcarbonyl, C2-C22 alko~ycarbonyl, C2-C22 haloalkyl carbonyl, C2-C22 haloalkoxycarbonyl, SRll, CHO, Cl-C4 alkylsulfonyl, phenylsulfonyl optionally substituted with 1 to 3 . ~
~, :

., , ~ , . .
.
,. ~ . ~ . ~ - .

S7~

substituents independently selected from W;
C7-C15 phenoxycarbonyl optionally substituted with 1 to 3 substituents selected f rom W; C7-C15 phenylcarbonyl optionally substituted with 1 to 3 substituents independently selected from W;
C(O)CO?Cl to Cg alkyl, C8-C12 ben~yloxycarbonyl optionally substituted with 1 to 3 substituents independently selected f rom W; or R5 and R6 are independently phenyl optionally substituted with 1 to 3 substituents independently selected f rom W, or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R7 is H, Cl-C4 alkyl or phenyl optionally substituted with W; SR8, SOR8, SO2R8, C(O)R8, CO2R~, C(O)NR8Rg, C~S)NR8Rg, C(S)R8, C(S)OR~, P(o)(OR~3)2, P(S)~R8)2' Pt)(R8)R8 or P(O) (R8)SR8; provided that wh~n R7 is other than COR8, C(O)NR8Rg or C(S)NR8Rg then R8 is other than H;
2S R8 is H, Cl-C6 alkyl, Cl-C6 haloalkyl, C4-C7 cycloalkylalkyl, C4-C7 halocycloalkylalkyl C:2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 ha lo a l kyny l , C2-C 6 a lkoxya l ky l , C2 -C 6 alkylthioalkyl, Cl-C6 nitroalkyl, C2-C6 cyanoalkyl, C3-C8 alkoxycarbonylalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, phenyl optionally substituted with 1 to 3 substituents independently selected from W

2~7'1~) or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
Rg i5 H~ C1-C4 alkyl, C2-C4 alkenyl~ C2-C~
alkynyl, or R8 and Rg is optionally taken together as ~CH2)4~ (CH2)5 or ~CH2c~2OcH2cH2);
Rlo is R8, halogen, CN, NO7, N3, SCN, OR8, SR8, SOR8, S02R8~ NRaRg~ COR8, C02R8, CONR8Rg~
S2NR8R9~ OC(O)R8~ 0C02R8~ OC(O)NRBRg, ; NRgC(O)R8~ NRgC(O)NR8Rg, OSO2R8, NRgSO2R8 or when p is 2, Rlo is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O, or CH2CH20 each of which is optionally substituted with - independently, 1 to 4 halogen atoms or 1 to 2 methyl groups;
Rll is Cl-C22 alkyl, CL-C22 haloalkyl, phenyl optionally substituted with 1 to 3 substitu~nts independently selected from W, or Rl1 is NR12C(~))R~3~ NRl2s(o)aRl3~

ZR14 ~R14 / R14 C(O)R13, N~12~16, S~lg, ~R12P\ , NR12P\ or P\
¦¦ZR15 IIR1S ¦¦ OR15 Y Y o R12 and R16 are independently selected from C
-C6 alkyl, Cl-C~ haloalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, C2-C6 : cyanoalkyl, C2-C6 alkoxyalkyl, C3-C~
alkoxycarbonylalkyl, C4-C~
dialkylaminocarbonylalkyl, phenyl optionally substituted by 1 to 2 substituents selected from ~, benzyl optionally substituted by 1 to 2 substituents selected from W and phenethyl optionally substituted by 1 to 2 .

7~

substituents selected from W, or R12-R16 is optionally taken together as (CH2~4, (CH2)5 or (CH2)20(CH2)2, each ring optionally substituted with 1 to 2 CH3;
R13 i5 F~ Cl-C20 alkyl, Cl-C6 haloalkyl, C2-C8 dialkylamino, piperidenyl, pyrrol-idenyl, morpholinyl, phenyl optionally sub-stituted with 1 to 3 substituents selected from W, or R13 is Cl-C20 alkoxy Cl-C6 haloalkoxy or Cl-C4 alkoxy substituted with cyano, nitro, Cl-C4 alkoxy, C4-C8 alkoxyalkoxy, Cl-C2 alkylthio, C2-C3 alkoxycarbonyl, C3-C5 dialkylaminocarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W, or R13 is phenoxy optionally substituted with 1 to 3 substituents sel~cted from W;
R14 and Rl~ are independently selected from Cl-C4 alkyl, C2-C4 haloalkyl, phenyl optionally substituted with 1 to 3 substi-tuents independentl~r selected from W or R14 and R15 is optional:ly taken together as (CH2)2, (CH2)3 or C1~2C~CH3)2CH2;
W is halogen, CN, N02, Cl-C2 alkyl, Cl-C2 haloalkyl, Cl-C2 alkoxy, Cl-C2 haloalkoxy, Cl-C2 alkylthio, Cl-C2 haloalkylthio, Cl-Cz alkylsulfonyl or Cl-C2 haloalkylsulfonyl;
m is 1 to 5;
n is 1 to 4;
t is O to 3;
q is O to 2;
p is 1 to 3;
a is O to 2;
V is O or S;
X is O or S;

.
:
. - . .;
.
, .. , . . : . ~ ::
,. . :

~o~

Y is O or S; and Z is O or S.

Preferred Compounds (A) are those compounds of Formula I wherein;
when R3 or R4 is H and A is oxygen then the remaining R3 or R4 is other than phenyl or phenyl optionally substituted with W and when t is 0 then R3 or R4 are other than Ph or phenyl optionally substituted with W.

Preferred Compounds (B) are Compounds of Formula I wherein;
Rl, R2 and Rlo are R8, halogen, CN, NO2, OR8, SR8, SOR8, SO2R8, NR~Rg, CO2R~, SO2NR8Rg, or when m, n or q is 2, then Rl, R~ or Rlo respectively is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O or CH2CH2O each of which is optionally substituted with 1 to 4 halogens or 1 to 2 methyl groups;
R8 is H, Cl-C6 alkyl, Cl-C6 haloalkyl, C3-C~ cycloalkylalkyl, C3-C6 halo-cycloalkylalkyl, C2-C6 alkenyl, C2 C6 haloalkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, phenyl optionally substituted with 1 to 2 substituents independently selected from W or benzyl optionally substituted with 1 to 2 substituents ~ independently selected from W;
- R5 and R6 are independently H, Cl-C3 alkyl, C2-C~ alkylcarbonyl, C2-C~
alkoxycarbonyl, CHO, SRll, phenyl optionally substituted with 1 to 2 substituents independently selected from W, or benzyl optionally substituted with .. ' : .. : ' ~.

X~Si~

1 to 2 substituents independently selected from W;
Rll is Cl-C3 alkyl, phenyl optionally substituted with 1 to 2 substituents independently selected from W, NR12C()R13, NR12S(O) aR13 ~ C(O)R13, NR12R16;

~ R14 ~ Rlg NR12~ or NR12P\
¦¦ ZRl5 llRl5 Y Y
R12 and R16 are independently selected from C1-C6 alkyl, Cl-C6 haloalkyl, C5-C6 cycloalkyl, C3-C8 alkoxycarbonylalkyl, phenyl, benzyl and phenethyl or each phenyl, benzyl and phenethyl optionally substituted with 1 to 2 substituents independently selected from W, or R12 and R16 can be taken together as (CH2)4, (CH2)s or (CH2)20(CH2)2;
R14 and R15 are independently selected from Cl to C3 alkyl or phenyl;
m is 1 to 2;
n is 1 to 2;
p is 1 to 2;
q is 0;
V is S; and a is 2.

Preferred Compounds (C) are Compounds B wherein:
R3 is H, Cl-C4 alkyl, Cl-C4 haloa]kyl, C2-C4 alkenyl, C2-C9 alkynyl, CN, phenyl optionally substituted with ~Rlo)p or benzyl optionally substituted with 1 to 2 `'~
. .
-, :

2~5t7~

substituents independently selected from W;
R4 is H, Cl-C3 alkyl, C3-C4 alkenyl or C3-C4 alkynyl;
R5 is H, Me, CO2Me, CO2Et, SRll or phenyl optionally substituted with 1 to 2 sub-stituents independently selected from W;
R6 is H, Me, C(O)Me, CO2Me or SRll;
Rll is Cl-C3 alkyl, NR12C~O)R13~
NR12~()aR13~ C(O)R13, or phenyl optionally substituted with Cl, NO2 or ~H3;

R12 is Cl-C9 alkyl or phenyl optionally substituted with Cl or CH3;
R13 is Cl-C12 alkyl, Cl-C12 alko~y~
Cl-C6 haloalkyl, dimethylamino, phenyl optionally substituted with Cl or CH3, or R13 is Cl-C9 alko~y substituted with C2-C4 alkoxy or 1 to 6 halogens;
A is CH2, CH2CH2, O, S, OCH2~ NR7 or SCH2 wherein, each carbon is optionally substituted with Cl-C3 alkyl or phenyl, wherein, the phenyl is optionally substituted with W; and;
R7 is H~ Cl-C4 ~lkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 alkylcarbo*yl, C2-C4 alkoxycarbonyl or Cl-C4 alkylsulfonyl.
Preferred Compound ~D~ are Compounds C wherein:
Rl and R2 are independently selected from F, Cl, Br, CN, NO2, OMe, CF3, OCF2H, OCF2CF2H, SMe, SO2Me, SCF2H or when m or n is 2 Rl or R2 respectively is : optionally taken together as CH2C(CH3)2O
or CF2CF2O;

: , , , '- '`: :

'7~

R3 is Cl to C4 alkyl, allyl, propargyl, or phenyl optionally substituted with F, Cl, Br, CF3, OCF2H, OCF3, SCF2H, CN, NO2, CH3, OMe or CO2Me;
R4 is H or CH3;
R5 is H, CH3 CO2CH3, CO2Et, or phenyl optionally substituted with F or Cl;
R6 is H, CH3, C(O)CH3 or CO2CH3; and A is O, S or CH2, optionally substituted with Cl-C3 alkyl or phenyl which may also be optionally substituted with W.

Preferred Compounds (E) are Compounds D wherein A is CH2; and R3 is optionally substituted phsnyl or Cl to C4 alkyl. Preferred Compounds (F) are compounds of Formula I wherein Q is Q-l. Preferred Compounds (G) are compounds of Formula I wherein Q is Q-2. Preferred Compounds (H) are compounds of Formula I wherein Q is Q3. :Preferred Compounds (I) are compounds of Formula I wlherein Q is Q4.
Preferred Compounds (J) are compounds of Formula I
wherein Q is Q5. Preferred Compounds (K) are compounds of Formula I wherein Q is Q6. Preferred Compounds (L) are compounds of Formula I wherein Q is Q7. Preferred Compounds ~M) are compounds of Formula I wherein Q is Q8. Preferred Compounds (N) are Compounds (E) wherein Q is Q-l.
3~
Specifically preferred are thQ compounds:
O~ 2-[5-fluoro-2-(4-fluorophenyl)-2,3-dihydro-lH-inden-l-yl-idene]-N-[9-(trifluoromethoxy)pllerlyl]hydrazine carbo~amide;

- ; ,.
. :

i '.. :

5'7~

P) 2-[6-chloro-2,3-dihydro-2-methyl-2 (2-propenyl)~3-benzo-furanylidene]-N-[4-(trifluoromethoxy)phenyl~hydrazine carboxamide;
Q) 2-(5-fluoro-2,3-dihydro-2-methyl -lH-inden-l-ylidene)-N-[4-(trifluoro methyl)phenyl]hydrazine carboxamide;
R) 2-[5-chloro-2,3-dihydro-2-(1-methylethyl) -lH-inden-l-ylidene]-N-~4-~trifluoro-methyl)phenyl]hydrazine carboxamide;
S) 2-(5-chloro-2,3-dihydro-2-methyl-lH
-inden-l-ylidene)-N-[9-(trifluoromethyl) phenyl]hydrazine carboxamide; and T) 2-[5-fluoro-2-(4-fluorophenyl)-2,3-dihydro -lH-.inden-l-yl-idene]-N-[4-(trifluoro-methyl)phenyl]hydrazine carboxamide.
DETAILS OF THE INVENTIQ~
The compounds of Formula I, where Q is Q-l, can : be prepared by the reaction of hydrazones of Formula II with an aryl isocyanate of Formula III. Compounds of Formula I, where Q is Q-2 through Q-8, can be prepared by procedures which are analogous to those : 25 for compounds where Q is Q-l; therefore, for brevity : only the Q-l compou~ds are described. Typical reactions involve combination of equimolar amounts of II and III in a suitable solvent at temperatures generally in the ran~e of -10 to 100C. Although the reaction can be run neat, a solvent is generally preferred. Suitable solvents typically have sufficient polarity to effect solution of the Formula II hydrazone and include, but are not limited to, ethers such as diethyl ether, tetrahydrofuran and dioxane; halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride;

', ~ , .

- , , ' -~ ~)Or~7~0 aromatic hydrocarbons such as benzene, toluene and xylene; esters such as ethyl acetate and polar aprotic solvents such as dimethylformamide and dimethylacetamide.

( R2) n~ I ~NCO 3~ I
N- NH
R5 (Rl)m II III

Compounds of Formula I include both geometrical and optical isomers as well as syn and anti isomers around the nitrogen-nitrogen bond. These isomers may vary in their biological activity. In some instances, it mày be desirable to obtain compounds which are geometrically and/or optically pure or which are enriched in one or more of the possible isomers. A11 such isomers are included within the scope of this invention.
For the sake of simplifying the description of this invention, the generic formula (Formula I) encompasses certain compounds that may have long term stability problems and/or are difficult to prepare.
For e~ample, when Rl is an OCO2R8 group and R8 is hydrogen the Rl substituent is OCO2H which will decompose to the corresponding phenol and carbon ~ dioxide. SimilarlY, haloalkylamines when Rl is NR8Rg ;~

~ ~ , and R8 is Cl to C6 haloalkyl are unstable when the halo substituent is directly adjacent to nitrogen.
These generally decompose to the corresponding hydrogen halides and imine. These compounds, however, are relatively few; their identity would be obvious to one skilled in the art, and their excision from the scope would unduly complicate and lengthen the description of the invention.
The hydrazones of Formula II can be obtained by processes known in the art involving condensation of a ketone of Formula IV with either hydrazine or a substituted derivative t'nereof (Formula V). This reaction is typically conducted with equimolar amounts of IV and V although greater than stoichiometric amounts of hydrazine (V) can be used.
Suitable solvents include the alcohols such as methanol, ethanol, propanol, butanol and the like at temperatures in the range of 0 to 150C, with the reflux temperature of the solvent generally being a convenient reaction temperature. Acid catalysis can also be useful, particularly for some of the more sterically hindered Formula IV compounds. Typical acid catalysts include sulfuric, hydrochloric and p-toluene sulfonic acid.

~1~2)n~?<~ ~ R5NHNH, ' II

IV V

.

X~ S7~1~

An alternate process useful for the preparation of compounds of Formula I involves condensation of a phenyl substituted semicarbazide of Formula VI with a ketone of Formula III. Preferred conditions for this reaction include an acid catalyst such as hydrochloric, sulfuric or p-toluene sulfonic acid.
Reaction temperatures can range from 0 to 150C with the reflux temperature of the solvent used generally preferred. Suitable solvents include, but are not limited to, ethers such as tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene and toluene; and especially preferred are alcohols such lS as methanol, ethanol and isopropanol.

HzN-7-C-MH ~ ,CRl)m ; 25 Compounds of Formula I where R5 and R6 are other than hydrogen can generally be prepared from the corresponding compounds where R5 and R6 are hydrogen by reaction with electrophilic reagents such as alkyl halides, acyl halides, alkyl chloroformates and sulfenyl halides. The use of a base is generally preferred in these reactions but is dependent upon the specific nature of the reactants. For example, ~0~57~

when the electrophilic reagent is selected from an alkyl halide, acyl halide or alkyl chloroformate, then metal hydrides such as sodium hydride or potassium hydride in solvents such as tetrahydrofuran or dimethylformamide are preferred. When ~ulfenyl halides are used then amine bases such as triethylamine in solvents such as diethyl ether or tetrahydrofuran are generally preferred. Of course, many of the compounds where R5 is oth~r than H can also be prepared by use of the appropriate hydrazine V in Scheme 2. For example, methyl hydrazine and methyl carbazate will produce compounds where R5 is methyl and carbomethoxy, respectively.
The starting ketones of Formula II are known or can be obtained by processes analogous to known ones. Those skilled in the art will recognize the Formula II compounds to include indanones, tetralones, chromanones, thiochromanones, benzofuran-3-ones, thiobenzofuran-3-ones, isochromanones, isothiochromanones and others.
The following Examples illustrate the invention.

Example 1 Step A: 3-chloro-a-(4-chlorophenyl)benzenepr~panoi~

To a solution of 6.8 g ~0.17 mol) of 60% sodium hydride in 150 ml of dimethylformamide under nitrogen was added 30.0 9 (0.162 mol) of methyl 4-chlorophenyl-acetate dropwise such that hydrogen evolution was moderate and the temperature of the reaction was maintained at less than 50C. Once hydroyPn evolution had ceased, a solution of 3-chlorobenzylbromide in 30 ml of dimethylformamide was added very cautiously such that the reaction temperature was maintained at less than 60C. The reaction was maintained at 50 to 60C with stirring 2~S7~0 overnight after which time it was partitioned between 5% aqueous NaHCO3 and diethyl ether, the aqueous e$.tracts were washed twice with ether and the combined organic extracts were then washed with water. The ether extracts were dried over MgSO4, filtered and concentrated to afford 48.0 g of a brown oil.
The crude product was combined with 300 ml of methanol, 40 ml of water and 20 ml of 50% aqueous sodium hydro~ide and reflu~ed overnight. After this time the reaction was concentrated and the crude residue partitioned between water and ether. The aqueous extracts were acidified with conc.
hydrochloric acid and extracted several times with ether. The ether extracts were dried over MgSO4, filtered and concentrated to 48.8 g of a yellow, oily solid.
lH NMR (CDC13) 6 3.0 (dd, lH), 3.3 (m, lH), 3.84 (t, lH), 6.77 (d, lH), 6.9-7.4 tm).

Step B: 5-chloro-2-(4-chlorophenyl!-2.3-dihydro-lH-inden-l-one The crude product from Step A was combined with S0 ml of thionyl chloride and then heated at reflu~
for 2 hours. Thionyl chloride was removed by concentration at reduced pressure and then the mixture was concentrated several times from carbon tetrachloride. The residue was combined with 200 ml of dichloroethane, cooled under nitrogen to 0C, and 24.5 g of aluminum trichloride was then added. After stirring overnight the reaction was poured onto a mixture of ice in lN hydrochloric acid, extracted three times with ether and chromatographed on silica gel ~10% ethyl acetate/hexane) to afford 18.6 g of a yellow oily solid~

.

2~ 0 H NMR (CDC13~ ~ 3.Z0 (dd, lH), 3.68 (dd, lH), 3.90 (dd, lH), 6.9-7.6 (m), 7.75 (d, lH).

Step C: 2-r5-chloro-2-(4-chlo{ophenyl)-2,3-dihydro lH-ind~en-l-ylidenel-N-r4 (trifluorome~hyl~-phenyllhydrazinecarboxamide A mixture of 1.5 9 of the indanone from Step B
and 0.75 ml of hydrazin~ hydrate in 10 ml of ethanol was refluxed under N2 overnight. The mixture was then partitioned between 5% Na~CO3 and ether, the aqueous extracts were washed with chloroform and the combined chloroform/ether extracts were washed with water. ~he organic extracts were dried over magnesium sulfate and concentrated to 1.54 9 of a yellow oil. To 0.45 g of th;is oil was added 10 ml of THF and 0.29 g of 4-trifluoromethylphenyl isocyanate. The mixture was then stirred under nitrogen overnight. Concentration at reduced pressure and then trituration with ether provided 0.27 g of the title compound as a yellow solidl m.p.
214 to 216C.
H NMR (CDC13~ ~ 2.95 (dd, lH), 3.74 tdd, lH), 4.30 (dd, lH), 7.1-7.8 (m), &.33 (s, lH); IR (nujol) 1~80, 3190, 3360 cm~l.

Ex~mple 2 Step A: eth~l 2r5-fluoro-2-(4-fluor~Ehenyl)-2.3-~i~y9~ L=l=ylidenelhydrazine car~oxylate To a mixture of 1.5 9 o~ 5-fluoro-2-(4-fluoro-phenyl)-2,3-dihydro-lH-inden-l-one (prepared by a procedure analogous to Example 1, Step ~) and 0.63 9 of ethyl carbazate in 20 ml of methanol was added 1 drop of conc. H2SO4 and the reaction was refluxed 2~ 7~L~

under nitrogen overnight. The reaction was then partitioned between ethyl acetate and 5% aqueous 5 NaHC03, the aqueous extracts were washed with ethyl acetate and the combined organic e~tracts were dried over MgS04. Concentration of the organic extract afford~d 1.9 g of a yellow oil, which was triturated with ether to afford 1.27 g of a white solid, m.p.
139-141C.
H NMR (CDC13) ~ 1.26 lt, 3H), 2.91 (dd, lH), 3.70 ~dd, lH), 4.2 (m, 3H), 6.9-7.3 (m, 6H), 7.52 (bs, lH), 7.93 ~dd, lH).

Step B: Q~hyl 2-~S-fluoro-2-(4-fluorophenyl)-2,3-dihydro-lH-inden-l-ylidenel-l- r rLs- ttri-fluoromethyl!phenyllami~olcarbonyll-hydrazine carboxylate To a solution of 1.0~ 9 of the ethyl carboxylate from Step A and 0.62 9 of 4-trifluoromethylphenylisocyanate in 10 ml of THF was added 0.26 ml o triethylamine and the mixture was stirred under nitrogen overnight. The reaction was then partitioned between ethyl acetate and ~% aqueous ` 25 NaHC03 and the aqueous extracts were washed twice with ethyl acetate. The organic extracts were dried over MgS04 and concentrated to 1.67 g o~ a yellow oil. Chromatography on silica gel afforded 0.37 g of a yellow solid m.p. 144-146.
lH NMR (CDC13) ~ 1.16 ~t, 3H), 3.00 (dd, lH), 3.65 (dd, lH), 3.8-3.9 (m, lH), 4.0-4.1 (m, lH), 4.32 (dd, lH), 6.85-7.2 (m, 6H), 7.60 (s, 4H), 8.05 (dd, lH), 10.66 (s, 1~).

~0~57~D

~xam~
Step A: N-r4-trifluoromethyl)phenyllhydrazine carboxami~
To a 0C solution of 10 ml of hydrazine hydrate and 75 ml of THF was added dropwise a solution of 6 g of 4-trifluoromethyl phenyl isocyanate in 20 ml of THF. After 1 hr TLC indicated the reaction was complete. The reaction was partitioned bet~een ether and water, the ether e~tracts were washed twice with water, dried over MgSO4, and concentrated to 6.34 g of a white solid, m.p. 168 172C.
lH NMR (CDC13) ~ 3.9 (bm, 2H), 6.1 (bs, lH), 7.56 (d, 2H), 7.61 (d, 2H), 8.4 (bs, lH).

Step B: m~Yl 5-chloro-2.3-dihydro-2-methyl-1-oxo-lH-indene-2-carboxY,l ~
To a mixture of 8.0 9 of S-chloroindanone and 4.2 ml of dimethylcarbonate in 60 ml of THF was added 4.0 g of 60% NaH and the mixture was heated to reflux under N2 overnight. After this time the reaction was cooled to room temperature alld 4.0 ml of methyl ; iodide was added and the mix~ure was reheated to 2$ reflux overnight. The reaction was then cooled and partitioned between ether and 5% aqueous NaHCO3 and the aqueous e~tracts were washed twice with ether.
The combined aqueous extracts were dried over MgSO4 and concentrat~d to 11.24 9 of a brown oil.
Chromatogrpahy on silica gel (10% ethyl acetate~hexane) afforded 4.25 9 of the title compound as a brown oil.
lH NMR (CDC13) ~ 1.52 (s, 311), 2.96 (d, lH), 3.S8 (s, 3H), 3.69 td, lH), 7.40 (d, lH), 7.47 (s, lH), 7.71 (d, lH~.

57fl~

Step C: mçthyl 5-chloro-2.3-dihYdrO-~-mÇthYl-l~
r ~ r r 4-~trifluorom~thyl)phenyl1aminol carbonyllhydrazin~J-LH-indene=2-carbQxyla~
To a mi~ture of 0.92 9 of the compound from Step A and 1.0 g of the compound from Step B in 10 ml of methanol was added 1 drop of conc. H2SO4 and the mi~ture was heated to reflux under N2 overniyht. The reaction was then cooled to 0C and the precipitate filtered, rinsed with cold methanol and dried to 0.39 9 of a brown solid, m.p. 192-194C.
lH NMR (CDC13) S 1.70 ~s, 3H), 3.00 (d, lH), 3.82 (s, 3H), 3.87 (d, lH), 7.3 (m, 2H), 7.6-7.8 (m, 5H), B.38 (s, lH), 8.98 (s, lH).

Exampl~. 4 Step A: 3-(4-fluorophenyl)-1-phenyl-2-propen-1-one To a mechanically stirred solution of 5.0 g NaOH in 35 ml H2O and 25 ml EtOH at 15C was added 12.0 9 (0.100 mole) of acetophenon~ and 12.4 g `` (0.100 mole) of 4-fluorobenzaldehyde. After a brief exotherm to 25C, the temperature returned to 15C, and the cooling bath was removed. The reaction mi~ture was stirred at room temperature for 1.5 hour, and the thick slurry was transferred to a beaker to cool overnig}~t at 10C. This mi~ture was filtered, and the solids were washed with distilled H?O until the washin~s were neutral to litmus. Upon drying in ; 30 vacuo, 20.8 9 of a pale yellow solid was obtained, m.p. 86-87C.
IR (Nujol)~: 1660, 1605, 1590, 1580 cm~l.
H NMR ~200 MHz, CDC13): 6 7.12 (d, J~16 Hz, lH), 7.42-7.68 (m, 7H), 7.78 (d, J=16 Hz, lH), 8.02 ~m, 2H)-~ trade mark for a mineral oil.

,~ '~ ' `
. , , , ' ~ ' ~

Step B: 3-t4-fl_Q~Q~heny1)-2 3-dihydro-lH-indene-l-onç
The title compound of Step A, Example 4, 11.3 g (0.50 mole), was added to 250 ml of mechanically-stirred polyphosphoric acid at 135~C, under a nitrogen atmosphere. This mixture was heated at 135C for 2 hours and then allowed to cool to 90C.
Ice water was added at such a rate as to maintain a temperature below 12SC. Once the material had become fluid, it was poured over ice and extracted with ether. The ether extracts were washed twice with saturated aqueous NaHCO3 and once with brine.
The ethereal solution was dried over MgSO4 and concentrated at reduced pressure. The resultant residue was recrystallized from he~ane/chlorobutane to afford 5.90 g of the title compound as a brown powder, m.p. 117-120C.
I~ tNUjol): 1705 (s), 1600 (br, m) H NMR (200 MHz, CDC13): ~ 2.64 (dd, lH), 3.22 ~dd, lH), ~.57 (dd, lH), 6.96-7.1~5 (m, 4H), 7.25 ~m, lH), 7.49 (m, lH), 7.58 (m, lH), 7.81 (m, lH).

Z5 Step C: 2-r3-(4-fluorophenylL-2~3-dihydro-lH-inden l=Ylidene~ 4-(trifluorometh~l~phen hy~lL__ e carboxamide The title compound of Step B, Example 4, 2.26 9 ~0.010 mole), was combined with 0.60 ml of hydrazine monohydrate (0.012 mole) in 30 ml of methanol and heated at reflux for 2 to 2.5 hours. The reaction mixture was concentrated at reduced pressure, and the resultant residue was dissolved in ethyl acetate and washed with saturated aqueous NaHCO3, H2O, and brine. The or~anic phase was dried over MgSO4 and concentrated in vacuo to afford 2.37 9 of crude material. This material was dissolved in 30 ml of 57~

dry THF, and a 10 ml aliquot of this solution was added to a solution of 0.62 g (0.0033 mole) of S 4-(trifluoromethyl)phenyl isocyanate in 20 ml of dry THF. After this mixture was stirred overnight under a nitrogen atmosphere, it was concentrated in vacuo.
The resultant residue was triturated with hexanes and filtered to obtain 1.23 g of an off-white product, m.p. 253-255~C.
H NMR ~200 MHæ, d6-DMSO): 6 2.74 (dd, lH), 3.38 (dd, 1~, 4.65 (dd, lH), 7.0-7.16 (m, 5H), 7.33-7.37 ~m, 2H~, 7.63-7.67 (m, 2H), 7.91-7.95 (m, 2H), 8.08 ~m, lH), 9.30 (s, NH), 10.00 (s, NH).
Example 5 Step A: ethyl 9-fl~Ls~c~ benzençacetate Sodium ethoxide solution was prepared by portionwise addition of sodium pieces ~1.5 9, 0.06~ mol) to ethanol (50 ml~. To this solution was added first, 8.9 ml (0.065 mol) of diethylo2alate in one portion and second, 10 g ~0.059 mol) of methyl 4-fluorobenzeneacetate dropwise at such a rate as to keep the reaction mixture at 25C. After stirring at room temperature for 2 hrs, the ethanol was concentrated and the residue taken up in toluene.
The toluene solution was concentrated and the solid residue was taken up in ether and 10% aqueous acetic ; acid. After stirring at room temperature for 1 hr the mixture was separated and the aqueous phase extracted twice with ether. The combined ether phases were washed once with saturated aqueous NaHCO3 solution, dried (MgSO4), and concentrated. The NMR
of the crudP product was complicated by a mixture of methyl and ethyl esters.

~5~

2~

The crude diester was combined witll 25 ml of water and 8 ml of 37% formalin solution. To this somewhat heterogeneous mixture was added 3 solution of 6.5 9 of K2CO3 in 36 ml of water, dropwise as such a rate as to maintain a temperature of about 25C.
The reaction was stirred vigorously for three hours to mix the fine ernulsion. Ether was added and the aqueous phase was separated and e~tracted three times with ether. The combined ether phases were dried (MgSO4) and concentrated to a colorless oil (11 g, 96% yield).
H NMR (CDC13) ~: 7.41 (2H, m), 7.03 (2H, m), 6.34 (lH, s), 5.8S (lH, s), 4.28 (2H, q, J=7 Hz~, 1.32 (3H, t, J~7 Hz).

Step B: ethyl 4-fluoro-a-L r (2-fluQroP~ l)thiol-~Q~Iyllbenzeneac~te The crude product from Step A (3.9 9, 20 mmole) was taken up in 20 ml of ethcinol. To this solution, being stirred at room temperature, was added 2-fluorothiophenol (2.5 g, 20 mmole) and 50 mg of solid sodium etho~ide. After stirring for eight hours the etllanol was concentrated and the residue taken up in ether. The ether mixture was washed twice with 15% NaOH solution, dried (MgSO4) and concentrated to a colorless oil ~5.3 9, 82% yield).
lH NMR ~CDC13) ~: 7.Z8 (9H, m), 7.06 (4H, m), 4.13 30 (2H, m), 3.72 (lH, m), 3.55 (lH, m), 3.20 (lH, dd, J=6, 12 Hz), 1.21 ~3H, t, J-6 Hz).

;i7~

Step C: 4-fluoro-a-ri(2-fluorophenyl~thiolmethyll-k~__eneacetic acid The crude ester from Step B (5.3 9, 16 mmole) was combined with 20 ml of 88% formic acid and 2.1 ml (33 mmole) of methane sulfonic acid. The emulsion was reflu~ed for five hours during which time it gradually became homogeneous. After cooling, water and methylene chloride were added and the aqueous phase was separated and extracted twice with methylene chloride. The organic phases were combined, dried (MgS~g) and concentrated. The crude residue was taken up in 4% ethyl acetate/he~ane and filtered through a plug of silica gel to remove nonpolar impurities. The product acid was then rinsecl rom the silica gel with ethyl acetate and the solvent concentrated. The acid was a colorless solid (9.5 g, 95% yield).
lH NMR (CDC13) ~: 10.05 (lH, br s), 7.20 (5H, m), 7.03 (3H, m), 3.81 ~lH, dd, J~6, 8 Hz), 3.57 (lH, m), 3.23 (lH, dd, J=6, 12 Hz).
;

Step D: 8-fluoro-~ fluorop~çnyl)-2 3-dihydro-4H-1-benæothiopyran-4-Q~
The acid from Step C (4.5 9, 15 mmole) was dissolved in 30 ml of thionyl chloride and reflu~ed for four hours. After cooling the thionyl chloride was concentrated and the residue taken up in carbon tetrachloride. The carbon tetrachloride was concentrated and the residue was taken up in 30 ml of dichloroethane. To the dichloroethane solution being cooled in an ice bath, was added aluminum trichloride (total of 2.1 9, 16 mmole) in three portions every 15 min. After stirring the black solution for an additional 30 min at 0C, a 5% aqueous HCl solution was added. The aqueous phase was separated and ' : ' ~' ' ' :' ~: ' ' Z~7~L~

2~

extracted twice with methylene chloride. The organic phases were combined, dried (MgSO~), and concentrated to give the crude product as a yellow oil (3.9 9, 82%
yield).
H NMR (CDC13) ~: 7.97 ~lH, dd, Js3~ 9 Hz~, 7.19 (6H, m), 4.12 (lH, dd, J-4, 12 Hz), 3.58 (lH, m), 3.32 (lH, ddm J=4, 12 Hz).
Step E: 2-L~-fluorQ-3~(4-fluo~Q~henyl)-3.4-dihydrQ-2H-l-benzothiopyran-4-ylidenel~M-t4,-~,tri-~l~oromethYl~phenyll-hydrazinecarboxamide Tlle thiochromanone from Step D ~1.1 9, 4.0 mmole) was treated according to the procedure in Example 1 Step C to give the desired procluct as a white powder (0.32 g, 17~ yield). m.pO , 217-219C.
lH NMR (CDC13) ~: 8.33 (lH, s), 7.98 (lH, d, J~9 Hz), 7.69 (lH, s) 7.60 (4H, AB, JAB-8 Hz), 7.15 (6H, m), 4.42 (lH, t, J~4 Hz), 3.44 (lH, dd, J=4, 12 Hz), 2.99 (lH, dd, J~4, 12 Hz).

Exampl,Q_~
Step A: methyl 6-fluoro-1.2.~ 4-tetrahydro-1-oxo-2-naDhthalenecarbo2YL~
Hexane washed sodium hydride ~3.5 9 of 60%, 88 mmole~ was covered with 75 ml of tetrahydrofuran and 5.4 ml (64 mmole) of dimethylcarbonate was added in one portion. The solution was heated to reflux and 6-fluoro-3,4-dihydro~1(2~)-naphthlenone ~7.2 9, 44 mmole) in 25 ml of tetrahydrofuran was added dropwise while maintaining reflux. After the addition was complete, the reaction was refluxed for 1.5 hours.
The reaction was then cooled in an ice bath and 10%
~5 aqueous ~Cl solution was carefully added. The solution was diluted with ether and the aqueous phase was separated and extracted twice with ether. The 2~57~

combined organic phases were dried (MgSO~) and concentrated. The crude product was a pale yellow solid (9.6 g, 98% yield).
lH NMR ~CDC13) ~: 7.99 (lH, dd, J=6,8 Hz), 6.95 (2H, m) 3.83 (3H, s), 3.B2 (lH, m), 2.81 (ZH, m), 2.58 (2H, m). NMR complicated by signals from enol tautomer.
Step B: methyl 6-fluoro-1 2 3 4-tetrahydro- _oxo-2-phenyl-2-naphthalenecarb~oxylate The tetralone from Step A (2.4 g, 10.8 mmole~
and triphenylbismuth dichloride (5.8 g, 11.3 mmmole) were dissolved in 50 ml of benzene. 1,8-Diazabicyclo-[5.4.0]-undec-7-ene (1.8 ml, 11.8 mmole) was added and the pale yellow solution was heated at reflux for 12 hours. The benzene solution was decanted from the gray sludge. The sludge was in turn triturated twice with ether and twice with acetone. The combined benzene, ether, and acetone phases were washed once with water, dried (MgSO4), and concentrated. The resulting residue was flash chromatographed on silica gel eluting with 10% acetone~hexane. Purifi~d product was obtained in 90~ yield (2.9 9~ as a YiscOuS oil which solidified on ~tanding.
H NMR (CDC13~ 6: 8.17 (lH, dd, J-8,10 Hz~, 7.31 (5H, m) 7.02 (lH, dt, J~3,8 Hz), 6.85 ~lH, dd, J=3,9 Hz~, 3.75 (~H, s~, 2.94 (2H, m), 2.B9 (2H, m).
Step C: 6-fluoro-~.4-dihxd~o 2-phenyl-1(2H)-naphthalenone The tetralone from Step B (2.B g, 9.4 mmole) was dissolved in 45 ml of dimethylformamide. To this solution was added lithium chloride ~2.0 g, 47 mmole) . , . ~: , 2~5~

2~

and water (0.42 ml, 23 mmole). The reaction mixture was heated to 150C for 2.5 hrs and then cooled and partitioned between ethex and water. The agueous phase was separated and e~tracted three times with ether. The combined organic phases were washed once with water, dried (MgSO4), and concentrated (1.96 g, 87% yield).
lH NMR (CDC13) ~: 8.13 ~lH, dd, J=6,10 Hz), 7.31 t5H, m) 6.99 (2H, m), 3.80 (lH, m), 3.07 (2H, m), 2.43 (2H, m).

; Step D: 2-(6-fluoro-1 2.3 4-tetrahydro-2-phenYl-l-naPhthalenYlidene)-N-r4-(trifluoromethYl) phenyllhydrazinecar~oX~mi~
The crude product from Step C (0.65 9, 2.7 mmole) was treated according to the procedure in Example 1, Step C. The product was obtained as a white powder ~0.26 9, 22% yield). m.p. ~ 158-160C.

lH NMR (CDC13) 6: 8.45 ~lH, s), 8.15 ~lH, d, J~9 Hz), 7.98 (lH, s), 7.61 (SH, m), 7.29 (2H, m), 7.18 (2H, m), 6.92 (lH, dd, J~3,9 Hz), 6.75 (lH, d, J,3 Hz), 4.18 ~lH, m), ~.64 ~2H, m), 2.31 (lH, m), 2.10 (lH, m).

~mEl~ 7 Step A: 4-Chloro-2-(2-me~hoxy-1-methyl-2-oxoethoxy)-~enzoic acid, methyl ester A solution of methyl 4-chlorosalicylate (S.0 9) in dimethylformamide (10 ml) was treated sequentially with methyl 3-bromopropionate (4.0 g) and potassium carbonate (6.0 9). The mixture was stirred at room temperature for 18 hrs and diluted with water. The mixture was extracted with ether and the organics ~ .

2~ 7~L~

were washed with water. The organic l~yer was dried and evaporated to give the desired material (6.7 9) S as a low melting solid.
NMR: 7.8 (d, lH), 7.2 (m lH), 6.9 (m, lH), 4.8 (q, lH), 3.9 (s, 3H), 3.8 (s, 3H), 1.7 ~d, 3H).

Step B: ~_chloro-2-methyl-3t2H!-benzofuranone `~ 10 A mixture of the compound of Example 7, Step A, (6.7 g) and sodium hydride (60% in oil, 1.5 9) was heated to reflu~ in tetrahydrofuran (50 ml). It was then allowed to cool to room temperature over 1.5 hrs. The cooled mixture was treated with aqueous ammonium chloride solution and ether. The ether solution was dried over magnesium sulfate and then evaporated. The oil was subjected to chromatography on silica gel with he~anes/ethyl acetate (25:1) as ; the eluent. The desired product (1.99 9) was obtained as a low melting solid.
NMR: 7.6 (d, lH), 7.1 (m 2H), 4.7 (q, lH), 1.5S (d, 3H).

Step C: ~ b~ hDl~2=2:methyl-3(2H~-~enzofuran 'dene)-N-~4-(tri~luoromethyl)phenylL-hydraæinecarboxamide The compound of Example 7, Step B, (1.9 9) was dissolved in ethanol (15 ml) and degassed with nitrogen. Then hydrazine hydrate (1.2 mlj was added and the mixture was heated at reflux for 1.5 hrs and evaporated to dryness. The residue was chromatographed on silica in hexanes~ethyl acetate (2:1). The first product eluted was the hydrazone syn to the methyl group S0.5 9). The ne~t fraction (o.g 9) was mixed syn and anti. Pure anti hydrazone was eluted last (0.5 9). l`he syn hydrazone was treated with p-trifluoromethylphenylisocyanate , .. .. ~ .

~, LO

(0.9 ml) in ether (10 ml). The desired material began to crystallize soon after mixing. The mi~ture was filtered and washed with ether to provide a solid (0.8 g). m.p.: 196-198C. NMR: 10.0 ~br/ lH), 9.4 (br, lH), 8.2-7.0 (m, 7H), 5.35 (m, lH), 1.6 (d, 3H).

Step D: ~E)-2-~6-chloro-2-methyl-3(2H~-benzofuranyl-idene)-N-[4-(~rifluoromethyl!phenyl)-hydrazinecarboxamide Treating the anti hydrazone (0.5 9) obtained in Step C with p-trifluoromethylphenylisocyanate (0.4 ml) in the same manner as in Step C resulted in the isolation of the desired product as a solid (0.8 9).
m.p. - 205-207C. NMR: (10.4 (br, NH), 9.4 (br, lH), 8.2-7.0 (m, 7H), 5.8 (m, lH), 1.47 (d, 3H).
By the general procedures described herein and obvious modifications known to one skilled in the art, one can prepare the compounds of Tables 1 to 16. The compounds of Tables 1 through 10 are listed along with their melting points.
In Tables 1 through 16 the following notations have been used:

1. 3,4-CF2CF2O is ~
~ F
F ~ F

2. 31 4-OCF2CFz 1~ --~F

O

3. 3, 4-CHaC~M~)aO is ~_0 4- 3, 4-OC(Me)2CH2 iS ~--~t--~0 ' ':' ' , ~ ;j i7~

5. ~en A i9 OCH2 or SCH2, the corrpound~ of ForJrula I are. rcRpQcti~rely, R2~_R3 or R2 ~R--4R3 N~

N~

6~ When A is CH20 or CH2S, t he cortpounds of Fornula I are, raspsctlvely, R2~
N~R4 c: r Rz -~R3 N~

5i74 [) ; 4 3 Z~ ~t R
N--N--R5 21 ~ ~

` R6 . .

~A = CH2, X = O) 20 CMPD Rl R2 ~ ~ ~ R6 m~

1 4-CF3 5-C1 4-Cl-Ph H H H 214-216 2 4-Br 5-C1 4-Cl-Ph H H H 230-232 3 4-OMe 5-C1 4-Cl-Ph H H H 202-204 : 25 4 4-C1 5-C1 4-Cl-Ph H H H 231-233 4-CF3 5-Cl Ph H H H 226-228 6 4-Br 5-Cl Ph H H H 237-238 7 4-OCF3 5-Cl Ph H H H 198-200 a 4-CF3 5-C1 4-F-Ph H H H 223-225 9 4-C1 5-C1 4-F-Ph H H H 224-226 : 10 g-Br 5-Cl 4-F-Ph H H H 230-232 11 4-CF3 5-F 4-Cl-Ph H H H 214-216 12 4-C1 5-F 4-Cl-Ph H H H 218-220 13 4-Fr 5-F 4-Cl-Ph H H H 223-225 1~ 4-CF3 5-F 4-F-Ph H H H 224-226 4-C1 5-F 4-F-Ph H H H 212-214 , ~5~7~

CMPD Rl ~ ~ ~ ~ R m.p.C

16 4-Br 5-F 4-F-Ph H H H 219-221 17 4-OCF3 5-F 4-F-Ph H H H 201-203 18 4-CF3 5-F Ph H H H 230-232 19 4-C1 5-F Ph HHH 233-235 4-Br 5-F Ph HHH 236-238 21 4-OCFj 5-F Ph HHH 187-190 22 4-CF3 5-OMe Ph HH H 219-221 23 4-OCF3 5-OMe Ph H H H 189-191 24 4-CF3 5-OMe 4-F-Ph H H H 197-199 4-CF3 S-OCH2CF3 4-F-Ph H H H 217-219 26 4-OCF3 5-OCH2CF3 4-F-Ph H H H 204-206 27 4-CF3 5-O-i-Pr 4-F-Ph H H H 198-201 28 4-CF3 5-OPh 4-F-Ph HHH 224-226 29 4-CF3 5-OEt 4-F-Ph HHH 206-208 4-OCF3 S-OEt 4-F-Ph HH H 195-197 31 4-Cl H Ph H H H 220-221 32 4-9r H Ph H H H 231-232 33 4-CF3 H Ph H HH 223-224 34 4-Cl H 4-F-Ph H H H 197-201 4-CF3 5-OH Ph H H H 240-242 36 4-CF3 5-Br 4-F-Ph H H H 218-220 37 4-9r 5-9r 4-F-Ph H HH 227-229 38 4-CF3 5-F 3-CF3-Ph H H H 225-227 39 4-~r 5-F 3-CF3-Ph H ~ H 221-223 4-CF3 5-F 2-F-Ph H H H 218-220 ql 4-9r 5-F 2-F-Ph HHH 231-233 42 4-CF3 5-F 3-F-Ph HHH 210-212 43 4-9r 5-F 3-F-Ph H H H 218-220 44 4-CF3 S-F 2,4-di-F-Ph H H H 219-221 4-~r 5-F 2,4-di-F-Ph H HH 214-216 46 4-CF3 5-F 4-OEt-Ph HH H 184-186 CMPD ~1 ~2 R3 B4 ~ ~ m.p.C

47 ~-CF3 5-F 4-Me-Ph H H H 219-221 48 4-Br S-F 4-Me-Ph H H H 227-229 49 4-CF3 S-F 2-naphthyl H H H 229-230 4-~r S-F 2-naphthyl H H H 230-232 Sl 4-CF3 S-F 3,4-di-Cl-Ph H H H 214-216 S2 4-CF3 4-F Ph H H H 214-216 53 4-Br g-F Ph H H H 222-224 S4 4-CF3 4-F 4-Cl-Ph H H H 236-238 4-OCF3 4-F 4-Cl-Ph H H H 209-211 56 2,4-di-C1 5-Cl Ph H H H >250 57 H 5-Cl Ph H H H 209-211 58 4-NO2 5-Cl Ph H H H >2S0 59 3,4-di-C1 5-F 4-F-Ph H H H 132-136 2,4-di-F 5-F 4-F-Ph H H H 213-215 61 4-F 5-F 4-F-Ph H H H 216-218 62 4-CF3 6-F 4-Cl-Ph H H H 237-239 63 4-C1 6-F 4-Cl-Ph H H H 236-238 64 4-Br 6-F 4-C1-Ph H H H 238-240 4-CF3 7-Cl Ph H H H 124-125 66 4-CF3 4,5-di-F 4-F-Ph H H H 233-235 67 4-OCF3 4,S-di-F 4-F-Ph H H H 224-226 68 4-8r 4,5-di-F 4-F-Ph ~ H H 229-231 69 4-CF3 5-C1 4-Cl-Ph Me H H 16S-169 4-~3r 5-C1 4-Cl-Ph Me H H 149-153 71 4-OMe S-Cl 4-Cl-Ph Me H H 187-190 72 4-CF3 5-F 4-F-Ph Me H H 85-89 73 4-Br S-F 4-F-Ph Me H H 70-74 74 4-CF3 S-Cl H H H H 240-242 7S 4-~r 5-Cl H H H H 244-246 76 4-Cl S-Cl H H H H 248-249 77 4-CF3 5-Cl Me H H H 208-210 :

, ~ '' . :

Z0~7 '~0 CMP~ ~1 R2 B~ R4 ~ ~ ~.p.C

78 4-C1 5-Cl Me H H H 221-223 79 4-~r 5-Cl Me H H H 228-230 4-CF3 7-Cl Me H H H ~250 81 4-CF3 5-F Me H H H 218-220 82 4-C1 5-F Me H H H 219-221 10 83 4-~r 5-F Me H H H 224-226 84 4-CF3 5-OMe Et H H H 191-193 4-OCF3 5-OMe Et H B H 178-180 86 4-CF3 5-Cl CO2Me H H H 242-244 ~7 4-CF3 5-F CO2Me H H H 238-240 15 88 4-CF3 5-Cl CO2Me Me H H 192-194 89 4-CF3 5-F CO2Me Me H H 203-205 4-CF3 5-Cl i-Pr H H H 216-218 91 4-OCF3 5-Cl i-Pr H H H 204-206 92 4-CF3 5-OCH2CF3 Me H H H 212-214 20 93 4-OCF3 s-OCH2CF3 Me H H H 189-191 94 4-C1 5-OC~2CF3 Me H H H 220-222 4-CF3 5-Cl Me Me H H 215-217 96 4-Br 5-Cl Me Me H H 214-216 97 4-C1 5-Cl Me Me H H 203-205 25 98 4-CF3 5-F i-Pr H H H 216-220 99 4-~r 5-F i-Pr H H H 217-222 100 4-CF3 5-F H H H H ~245 10Z 4-Br 5-F H H H H ~245 30103 4-CF3 5-F 4-F-Ph H C(O)Me H oil 104 4-OCF3 5-F 4-F-Ph H C(O)Me H oil 105 4-CF3 5-F 4-F-Ph H CO2Me H oil 106 4-CF3 5-F 2 4-di-Ph H COzMe H oily solid 35107 4-CF3 5-F 4-F-Ph H CO2Et ~ 144-146 108 4-Pr H 4-F-Ph H H 8 204-207 .

~si~

CMPD ~ R2 ~ ~ ~ ~ m D. C

109 4-CF3 H 4-F-Ph H H H 212-213 110 4-C1 4-Cl Ph H H H 234-239 111 4-~r 4-Cl Ph H H H 283-285 112 4-CF3 4-Cl Ph H H H 205-209 113 4-CF3 5-Me 4-Cl-Ph H H H 210-214 114 4-~r 5-Me 4-Cl-Ph H H H 260-262 115 4-C1 5-Me 4-Cl-Ph H H H 270-272 116 4-CF3 4-C1 4-F-Ph H H H wax 117 4-Br 4-C1 4-F-Ph H H H wax 118 4-C1 4-C1 4-F-Ph H H H wax 119 4-CF3 5-F CH2Ph-4-F CH2Ph-4-F H H 76-81 120 4-C1 5-F C}I2Ph-4-F CH2Ph-4-F H H 84-89 ~ .

~5~4il~

3a ~2 ~ll R4 N--N~R; R, R~

(A = CH2CH2, X = O) CMPD Rl ~ ~ B4 121 4-Br 5-Cl Ph H H H 209-210 122 4-CF3 S-Cl Ph H H H 217-218 123 4-C1 5-C1 4-Br-Ph H H H 236-238 124 4-Br 5-Cl i-Br-Ph H H H 248-250 : 25 125 4-CF3 5-C1 4-Br-Ph H H H 245-247 126 ~-Cl S-Cl 4-OMe-Ph H H H 209-210 127 4-Br 5-C1 4-OMe-Ph H H H 216-217 12B 4-CF3 5-C1 4-OMe-Ph H H H 226-228 129 4-C1 5-Cl Me H H H 236-238 30 130 4-Br 5-Cl Me H H H 230-235 131 4-CF3 S-Cl Me H H H 234-235 132 4-CF3 S-Cl CO2Me H H H 220-222 133 4-Rr 5-C1 4-F-Ph H H H 221-222 134 4-CF3 5-Cl 4-F-Ph H H H 233-234 35 135 4-CF3 5-Cl H H Me H 114-117 136 4-Cl 4-F Me H H H 233-236 .: ' ,. : , 2~)~57~

CMPD Rl ~2 ~ ~.p. C

137 4-Br 4-F Me H H H 236-239 138 4-CF3 4-F Me H }I H 235-237 139 4-C1 5-F Ph H H H 179-184 140 4-Br S-F Ph H H H 185~192 191 4-CF3 5-F Ph H H H 158-160 142 4-CF3 4_p CO2Me H H H 203-204 143 4-CF3 5-F 4-F-Ph H H H 179-180 144 4-CF3 5-F 4-Cl-Ph H H H 225-230 145 4-C1 5-F Me H H H 200-210 146 4-Br 5-F Me H H H 196-198 147 4-CF3 5-F Me H H H 195-198 148 4-CF3 H CO2Me H H H 207-208 149 4-CF3 H CO2Me H Me H oil 151 4-CF3 H 4-Cl-Ph H H H 22a-230 2 0 152 4-OMe H 4-Cl-Ph H H H 191-193 153 4-F H 4-Cl-Ph H H H 204-205 154 3-CF3 H 4-Cl-Ph H H H 199-200 155 3-CO2Et H 4-Cl-Ph H H H 205-206 156 4-F,3-Cl H 4-Cl-Ph H H H 210-212 ~5 157 4-CF3 5-Br H H H H 253-255 ' -: .'' , `,, :' ~ :
:: :; .:. . .. , .~
.. :. :,.'. :' ' ;:

~0~57~( 1 ~ 3 ~ l~l Ri C~ X) N~

(A = ~CH2)3, X = O~

Ç~ ~ ~ m.p.C

159 4~CF3 5-Cl H H H H 224-225 160 4-C1 5-Cl H H H H 211-213 161 4-~r 5-Cl H H H H 210-213 162 4~CF3 5-Cl Me H H H 174-176 3~

.: .
:-.

2~ 4~

R2 ~ 1~ R4 N--N-~5 ~ R

(X = O) CMPD R~ 4 ~ ~6 ~ ~.p.C

163 4-Cl H Me Me H H O 177-182 164 4-CF3 H Me Me H H O 186-188 165 4-CF3 5-Cl Me Me H H O 214-217 166 4-C1 5-Cl Me Me H H O 204-207 167 4-Br 5-Cl Me Me H H O 204-20a 168 4-CF3 4-F Me Me H H O 203-206 169 4-C1 4-F Me Me H H O 193-196 170 4-Br 4-F Me Me H H O 194-198 171 4-CF3 5-Cl Me 4-F-Ph H H O 219-220 172 4-C1 5-Cl Me 4-F-Ph H H 0 209-211 173 4-CF3 H Me Ph H H O 174-176 174 4-Cl H Me Ph H H O 165-lS7 175 4-Br H Me Ph H H O 165-166 176 4-CF3 5-Cl Me Et H H O 190-192 177 4-CF3 S-Cl Me allyl H H O 150-152 ..' 2~7~

CMPD ~ B2 ~ R4 ~ ~ A ~ S

178 4-C1 5-Cl Me allyl H H O 142 145 179 4-CF3 5-CF3 Me Me H H O 234-236 180 4-OCF3 5-CF3 Ma Me H H O 196-199 181 4-OCP3 5-Cl Me allyl H H O 128-130 lB2 4-Cl H Me Me Me Me O 155-158 183 4-Cl H Me Me Me H O wa~
184 4-CF3 El Ph Me Me Me O 128-130 185 4-CF3 H Me Me H H S 193-197 186 4-Cl H Me Me Me M~ S 192-193 ~0 X~ 4~

TAB~

~I R
N - NH
CONH~

(A = O) ~ 2 ~ ~ Y~anti ~

187 4-CF3 H Me H syn 179-180 188 4-CF3 H Me H antt 212-213 189 4-CF3 S-Cl Me H syn 196-198 190 4-CF3 5-Cl Me H anti 205-207 191 4-Br H Me H mix 193-196 192 4-Br 5-Cl Me H mix 195-200 193 4-CF3 H i-Pr H syn 201-202 194 4-CF3 H i-Pr H anti 181-183 195 4-Cl H i-Pr H sy~ 151-153 196 4-Cl H i-Pr H mix 203-205 197 4-Br H i-Pr H mix 200-20S
198 4-CF3 5-Cl i-Pr. H syn 195-196 199 4-Br S-Cl i-Pr H mix 197-199 200 4-C1 5-Cl i-Pr H anti 192-196 201 4-CF3 5-Cl i-Pr H mix 196-200 , ~ ': . ~ '. ' . ' ' ~
, ~5~

R2~
C( X) N~Rt (A = CH2, X = S) ~PD Bl ~ ~ ~ B5 B6 m .p. C

Z02 4-CF3 5-F 9-F-Ph H H H 192-194 203 4-CF3 5-F Ph ` H H H 154-156 204 4-Cl S-F4-F-Ph H H H 182-184 205 4-Br 5-Cl Ph H H H 192-194 ' . "

2~57~

R~Rb 10 R2 ~[~R~, N-NH
CON~

C~PD ~ ~ ~ ~ ~ m.p.C

20~ 4-CF3 5-F 4-F-Ph Me H 218-220 207 4-CF3 5-Cl H i-Pr H 238-240 208 4-CF3 5-F H Me H 241-243 209 4-OCF3 5-F H Me H 211-213 210 4-CF3 H H Me Me 222-223 211 4-Cl H H Me Me 215-216 212 4-CF3 5-F H Me Me 198-201 213 4-F 5-F H Me Me 201.5-205 214 4-CF3 H H Ph H 248.5-250 215 4-Cl H H Ph H 253-254 216 4-CF3 H B Ph Me 207-209 217 4-Cl H H Ph Me 203-205 218 4-CF3 H H 4-Cl-Ph H 243.5-245 219 4-Cl H H 4-Cl-Ph H 242.5-244 220 4-CF3 5~Cl H Ph H 246-248 221 4-8r 5-Cl H Ph H 256-258 222 4-CF3 5-Cl H 4-Cl-Ph H 235-238 ::: :: : : . :

~: : : : :: .

Z~ ;7~0 CMPD Rl R2 R3 ~ ~ m p.C

S 223 4-Br 5-C1 ~ 4-Cl-Ph ~ 260-262 224 4-CF3 H ~ 4-F-Ph H 253-255 225 4-Cl H H 4-F-Ph H 2~9-250 226 4-F H H 4-F-Ph H 244-246 227 4-CF3 5-F H Ph H >250 228 4 Cl 5-F H Ph H >250 229 4-CF3 4-Cl H 4-F-Ph H 252.5-253 230 4-C1 4-Cl H 4-F-Ph H 260-261 231 4-CF3 4-C1 H 4-F-Ph M~ 176-179 232 4-CF3 4-F H 4-F-Ph H 242-244 233 4-C1 4-F H 4-F-Ph H 248-250 ~35~

Rz C( O) NH~R

S~ m p.C

234 4-C1 5-Cl Ph H H O 180-182 235 4-Br 5-Cl Ph H H O 189-191 236 4-CF3 5-Cl Ph H H O 211-212 237 4-C1 5-C1 4-F-Ph H H O 171-173 238 9-Br 5-C1 4-F-Ph H H O 187-189 239 4-CF3 5-C1 4-F-Ph H H O 180-185 240 4-CF3 5-F Ph H H O 197-200 241 4-Br 5-F 4-F-Ph H H O glass 242 4-CF3 5-F 4-F-Ph H H O glass 243 4-C1 5-C1 4-F-Ph H H S 216-218 244 4-Br 5-C1 4-F-Ph H H S 219-221 245 4-CF3 5-C1 4-F-Ph H H S ~220 246 4-C1 5-Cl Ph H H S 194-196 247 4-Br 5-Cl Ph H H S 210-212 248 4-CF3 S-Cl Ph H ~ S 205-208 249 4-C1 5-C1 4-Cl-Ph H H S 184-186 250 4-Br 5-C1 4-Cl-Ph }I H S 199-201 : ',' , : .:, 7~6D

CMPD ~1 ~ R3 R4 ~ ~ mh~

251 4-CF3 5-C1 4-Cl-Ph H H S 207-210 252 4-C1 4-F 4-F-Ph H H S 216-218 253 4-Br 4-F 4-F-Ph H H S 218-220 254 4-CF3 ~-F 4-F-Ph H H S 217-219 255 4-C1 4-F Ph H H S 195-197 256 4-CF3 4-F Ph H H S 208-210 257 4-C1 5-F 4-F-Ph H H S 209-211 258 4-Br 5-F 4-F-Ph H H S 215-217 259 4-CF3 5-F 4-F-Ph H H S 202-204 260 4-CF3 H H H H C(Me)2 206-210 261 4-Cl H H H H C~Me)2 208-212 262 4-OMe H H H H C(Me)2 177-180 : :
'.

:

7'~C~

~ABLE~!

R ~ ~d C{ O;N~R

.

CMPD ~1 R2 264 4-CF3 S-Cl H H Me Me ~ 151-153 265 4-CF3 5-Cl H Me Me H S >250 266 4-CF3 5-Cl H H H Me S 234-235 267 4 CF3 5-Cl H H MQ Me O 253-255 .

~5 . . `. ,. .-. .

7~

Q- NHCNH~F3 C?`~PD Q v A ~ ~ B4 m . p . c 268 Q-5 - C82CH2 ~I H H 173-174 269 Q-6 S C82CH2 H H El 248-249 :~ :

.

~s~

T~E~LE~

N~NH ~

~ 4 Blo 4-OCF3 4-~ H H CH2 3,4-di-C1 4-F H ~ C~2 4-CN 4-Cl H H CH2 4-CO2Me 4-Cl H H C~2 4-OCF2H 4-Cl H H CH2 4-OCF3 4-Cl H H CH2 4-OCF2H 5-F H H CHz 4-OCF2CF2~ 5-F H H CH2 3,4-CF2CF20 5-F H H CH2 3,4-CH2C(Me)20 5-F H H CH2 , ~

Rl ~2 ~ ~10 A

4-F S-Cl ~ H CH2 4-C1 5-Cl H H CH2 4-OCF2H S-Cl H H CH2 4-NO2 S-Cl H H CH2 4-SCF2H 5-Cl H H CH2 4-CN 5-Cl B H CH2 3,4-CF2CF20 5-Cl H H CH2 3t4-cH2c(Me)2o 5-Cl H H C~2 4-Cl S-Br H H CH2 4-'Br 5-Br H H CH2 4-CF3 5-Br H H C~2 4-OCF2H 5-Br H H CH2 4-OCF3 5-Br H H CH2 4-Br 5-CN H H CH2 4-C1 5-OMe H H CH2 4-Br 5-OMe H H CH2 4-Br , s-CF3 B H CH2 4-Br 5-OCF2H H H CH2 "

, 2~ 7~t~) Rl ~ R4 -10 A

4-C1 5-OCF3 H H C~2 4-Br 5-OCF3 H H CH2 4-OCF2H 5-OPh H H CH2 4-OCF3 5-OPh ~ H CH2 4-CF3 5-OPh H H CH2 4-C1 5-OPh H H CH2 4-Br 5-OPh H H CH2 4-CF3 5-SMe H H CH2 4-C1 5-SMe H H CH2 4-8r 5-SMe H H CH2 4-~3r 6-F H H CH2 4-CF3 6-Cl H H CH2 4-C1 6-Cl H H CH2 4-Br 6-Cl H H CH2 4-CN 5-F H 4-F CH~
~5 4-OCF2CF2H 5-F H 4-F CH2 3,4-di-C1 5-F H 4-F CH2 3,4-CF2CF20 5-F H 4-F CH2 3,4-CH2C(Me)20 5-F H 4-F CH~
4-OCF2H 5-F H 4-Cl CH2 4-OCF3 5-F H 4-Cl CHz 4-C1 5-F H 4-NO2 CHz 4-Br 5_~ H 4-NO2 CH2 4-CF3 5-F H 4-N~2 CH2 57~L 1) ~1 Rz ~ Rlo A

4-Br 5-F H 4-CN CH2 4-CF3 5-F H 4-CN C~2 4-OCF3 5-F H 4-CN C~2 ~-Cl 5-F ~ 4-OMe CH2 4-Br 5-F H 4-OMe CH2 4-CF3 5-F H 4-OMe CH2 4-OCF2H 5-F H 4-OMe CH2 4-OCF3 5-F H 4-OMe CH2 4-Br 5-F H 4-CF3 CH2 4-Br 5-F H 4-OCF2H CH2 4-OCF2CF2H 5-Cl ~ H 4-F CH2 4-F 5-Cl H 4-F CH2 4-OCF3 5-Cl H 4-F CH2 4-OCF2H 5-Cl H 4-F CH2 4-NO2 5-Cl H 4-F CH2 3,4-di-C1 5-Cl H 4-F CH2 3,4-CH2C(Me)20 5-Cl H 4-F CH2 3,4-CF2CF20 5-Cl H 4-F CH2 4-OCF3 5-Cl H 4-Cl CH2 4-OCF2H 5-Cl H 4-Cl CH2 3,4-CF2CF20 5-Cl H 4-Cl CH2 '; ' `

,, : - ', .
, - , . , 20~

Rl R2 ~ RlQ A

3,4-CH2C(Me)20 5-Cl H 4-Cl CH2 4-CN 5-Cl H 4-Cl CH2 4-F 5-C1 H 4-Cl CH~
4-NO2 5-C1 H 4-Cl CH2 ~ H 5-Cl H 4-Cl CH2 4-CF3 5-CF3 ~ 4-F CH2 4-OCF3 5-CF3 H 4-F C~2 4-Br 5-CF3 H 4-F CH2 4-CF3 5-CF3 H 4-Cl CH2 : 4-OCF3 5-CF3 H 4-Cl C~2 4-C1 5-CF3 H 4-Cl CH2 4-Br 5-CF3 H 4-Cl CH2 4-OCF2H S-CF3 H 4-Cl CH2 4-Br 5-OCF2H H 4-F CH2 4-CF3 5-OCF2H H 4-Cl CH2 4--C1 5-OCF2H H 4-Cl CH2 4-Br 5-OCF2H H 4-Cl C~2 : 4-OCF3 5-OCF~H H 4-Cl CH2 4-CF3 4-F H 4-F C~2 4-C1 4~F H 4-F CH2 4-Br 4-F H 4-F C~2 4-CF3 4-F H 4-Cl CH2 4-C1 4-F H 4-Cl CH2 4-Br 4~F N 4-Cl CH2 q-CF3 4-Cl H 4-Cl CH2 4-C1 4-Cl H 4-Cl CH2 4-Br 4-Cl H 4-Cl CH2 20~ :~7~

Rl B2 ~L --10 4-OCF3 4-Cl H 4-Cl CH2 4-CF3 4-Cl H 4-F C~2 4-C1 4-Cl H 4-F CH2 4-8r 4-Cl H 4-F CB2 4-OCF3 4-Cl H , 4-F C~2 4-CF3 5-C1 ~ 4-CF3 CH2 4-C1 5-C1 ~ 4-CF3 CH2 4-Br 5-Cl H 4-CF3 CH2 4-OCF3 5-Cl H 4-C~3 CH2 4-OCF2H 5-Cl H 4-CF3 C~2 4-CF3 5-Cl H 4-SMe CH2 4-C1 5-Cl H 4-SMe CH2 4-Br 5-Cl H 4-SMe CH2 4-OCF3 5-Cl H 4-SMe CH2 4-CF3 5-Cl H 4-NO2 CH2 4-C1 5-Cl H 4-NO2 CH2 4-Br 5-Cl H 4-NO2 CH2 4-OCF2H 5-Cl H 4-N2 CH2 4-CF3 5-Cl H 4-OMe CH2 4-C1 5-Cl H 4-OM~ CH2 4-Br 5-Cl H 4-OMe CH2 4-OCF2H 5-Cl H 4-OMe CH2 4-CF3 5-Cl H 4-OPh CH2 4-C1 5-Cl H 4-OPh CH2 4-8r 5-Cl H 4-OPh CH2 4-OCF2H 5-Cl H 4-OPh CH2 4-CF3 5-Ci H 4-CN CH2 4-C1 5-Cl H 4-CN CH2 4-Br 5-Cl H 4-CN CH2 4-OCF2H 5-Cl H 4-CN CH2 4-CF3 5-C1 ~ 4-CO2Me C~2 4-C1 5-Cl H 4-CO2Me C~2 4-Br 5-Cl H 4-CO2Me CH2 : ' ' ` i` '~.

-1 R~ ~4 4-CF3 H Me ~ CH2 4-Cl H Me H CH2 4-Br H Me H CH2 4-OCF2H H Me H CH2 4-OCF3 H Me H CH2 4-CF3 4-F Me H CH2 4-C1 4-F Me H CH2 4-Br 4-F Me H CH2 4-OCF2H 4-F Me H CH2 4-OCF3 4-F Me H CH2 lS 4-CF3 4-Cl Me H CH2 4-C1 4-Cl Me H CH2 4-Br 4-Cl Me H CH2 4-OCF2H 4-Cl Me H CH2 4-OCF2H 4-Cl Me H CH2 4-CF3 5-F Me H CH2 4-C1 5-F Me H CH2 4-Br 5-F Me H CH2 4-OCF2H S-F Me ~ CH2 4-CF3 5-Cl Me H CH2 4-Cl S-Cl Me H CH2 4-Br S-Cl Me H CH~
4-OCF2H 5-Cl Me H CH2 4-CF3 4-F Me 4-F CH2 4-C1 4-F Me 4-F CH2 4-Br 4-F Me 4-F CH2 4-OCF2H 4-F Me 4-F C~2 4-CF3 4-Cl Me 4-F CH2 4-Cl 4-Cl Me 4-F CH2 4-Br 4-Cl Me 4-F CH2 7~i R~ 10 4-OCF2H 4-Cl Me 4-F CH2 4-CF3 5-F Me 4-F CH2 4-C1 5-F Me 4-F CH2 4-Br 5-F Me 4-F CH2 4-OCF2H 5-F Me 4 F CH2 10 4-CF3 5-Cl Me 4-F CH2 4-Cl S-Cl Me 4-F CH2 4-Br 5-Cl Me 4-F CH2 4-OCF2H 5-Cl Me 4-F CH2 4-CF3 4-F Me 4-Cl CH2 15 4-C1 4-F Me 4-Cl CH2 4-Br 4-F Me 4-Cl CH2 4-OCF2H 4-F Me 4-Cl CH2 4-CF3 4-Cl Me 4-Cl CH2 4-C1 4-Cl Me 4-Cl CH2 20 4-Br 4-Cl Me 4-Cl CH2 4-OCF2H 4-Cl Me 4-Cl CH2 4-CF3 5-F Me 4-Cl CH2 4-C1 5-F Ms 4-Cl CH2 4-Br 5-F Me 4-Cl CH2 25 4-OCF2H 5-F Me 4-Cl CH2 4-CF3 5-Cl Me 4-Cl CH2 4-C1 5-Cl Me 4-Cl CH2 4-~r 5-Cl Me 4-Cl CH2 4-OCF2H 5-Cl Me 4-Ci CH2 30 4-CF3 5-Cl Me 4-Cl CH2 4-C1 5-Cl Me 4-Cl CH2 4-Br 5-Cl Me 4-Cl CH2 4-OCF2H 5-Cl Me 4 Cl CH2 4-CF3 5-Cl Et 4-F CH2 35 4-C1 5-Cl Et 4-F CH2 4-Br S-Cl Et 4-F CH2 - , --1 R2 ~ Rlo ,~

4-CF3 5-Cl Et 4-Cl CM2 4-C1 5-Cl Et 4-Cl CH2 4-Br 5-Cl Et 4-Cl CH2 4-CF3 5-Cl allyl 4-F CH2 4-C1 5-Cl allyl 4-F CH2 4-Br 5-Cl allyl 4-F CH2 4-CF3 5-Cl allyl 4-Cl CH2 4-C1 5-Cl allyl 4-Cl CH2 4-Br 5-Cl allyl 4-Cl CH2 4-CF3 5-Cl propargyl 4-F C~2 4-C1 5-Cl propargyl 4-F CH2 4-Br 5-Cl propargyl 4-F CH2 4-CF3 5-Cl propargyl 4-Cl CH2 4-C1 5-Cl propargyl 4-Cl CH2 4-Br 5-Cl propargyl 4-Cl CH2 4-OCF3 5-Cl H 4~F O
4-CF~ 5-CF3 H 4-F O

4-CF3 5-Cl H 4-F S
4-OCF3 5-Cl H 4-F S
: 4-CF3 5-CF3 H 4-F S

. ~

, . ~

x~

Rl ,~ ~ Rlo 4-CF3 H Me H O
4-Cl H Me H O
4-Br H Me H O
4-OCF2H H Me H O
4-OCF3 H Me H O
10 4-CF3 4-F Me H O
4-C1 4-F Me H O
4-Br 4-F Me H O
4-OCF2H 4-F Me H O
4-OCF3 4-F Me H O
15 4-CF3 4-Cl Me H O
4-C1 4-Cl Me H O
4-Br 4-Cl Me H O
4-OCF2H 4-Cl Me H O
4-OCF3 4-Cl Me H O
20 4-CF3 5-F Me H O
4-C1 5-F Me H O
4-Br 5-F Me H O
4-OCF2H 5-F Me H O
4-CF3 5-Cl Me H O
25 4-C1 5-Cl Me H O
4-Br 5-Cl Me H O
4-OCF3 5-Cl Me H O
4-OCF2H 5-Cl Me H O
4-CF3 4-F Me 4-F O
30 4-C1 4-F Me 4-F O
4-Br 4-F Me 4-F O

4-OCF2H ~-F M~ 4-F O
4-CF3 4-Cl Me 4-F O
35 4-C1 4-Cl Me 4-F O
4-Br 4-Cl Me 4-F O
4-OCF3 4-Cl Me 4-F O

:
- . .

: i L ~ ; ~

7~

~1 ~2 ~4 Rlo 4-OCF28 4-Cl Me 4-F O
4-CF3 5-F Me 4-F 9 4-C1 5-F Me 4-F O
4-Br 5-F Me 4-F O
4-OCF3 5-F Me 4-F O
4-OCF2H 5-F Me 4-F O
4-CF3 5-Cl Me 4-F O
4-C1 5-Cl Me 4-F O
4-Br 5-Cl Me 4-F O
4-OCF3 5-Cl Me 4-F O
4-OCF2H 5-Cl Me 4-F O
4-CF3 4-F Me 4-Cl O
4-C1 4-F Me 4-Cl O
4-8r 4-F Me 4-Cl O
4-OCF3 4-F Me 4-C1 4-OCF2H 4-F Me 4-Cl O
4-CF3 4-Cl Me 4-Cl O
4-C1 4-Cl Me 4-Cl O
4-Br 4-Cl Me 4-Cl O
4-OCF3 4-Cl Me 4-Cl O
4-OCF2H 4-Cl Me 4-Cl O
4-CF3 5-F Me 4-Cl O
4-C1 5-F Me 4-Cl O
4-Br 5-F Me 4-Cl O
4-OCF3 5-F Me 4-Cl O
4-OCF28 5-F Me 4-Cl O
4-CF3 5-Cl Me 4-Cl O
4-Cl 5-Cl Me 4-Cl O
4-Br 5-Cl Me 4-Cl O
4-OCF2H 5-Cl Me 4-Cl O
4-OCF3 5-Cl Me 4-Cl O
4-CF3 S-Cl Me 4-Cl O
4-C1 5-Cl Me 4-Cl O

~5~

~1 R2 ~ --10 4-~r 5-Cl Me 4-Cl O
4-OCF3 5-Cl Me 4-Cl O
4-OCF2H S-Cl Me 4-Cl O
4-CF3 5-Cl Et 4-F O
4-C1 5-Cl Et 4-F O
4-Br 5-Cl Et 4-F O
4-CF3 5-Cl Ft 4-Cl O
4-C1 5-Cl Et 4-Cl O
4-Br 5-Cl Et 4-Cl O
4-CF3 5-Cl allyl 4-F O
4-C1 5-Cl allyl 4-F O
4-Br 5-Cl allyl 4~F O
4-CF3 5-Cl allyl 4-Cl O
4-C1 5-Cl allyl 4-Cl O
4-~r 5-Cl allyl 4-Cl O
4-CF3 5-Cl propargyl 4-F O
4-C1 5-Cl propargyl 4-F O
4-~3r S-Cl propargyl 4-F O
4-CF3 5-Cl propargyl 4-Cl O
4-C1 5-Cl propargyl 4-Cl O
4-Br 5-Cl propar~yl 4-C1 o 4-CF3 H Me H S
4-Cl H Me H S
4-Rr H Me H S
4-OCF2H H Me H S
4-OCF3 H Me H S
4-CF3 4-F Me H S
4-C1 4-F Me H S
4-Br 4-F Me H S
4-OCF2H 4-F Me H S
4-OCF3 4-F Me H S
4-CF3 4-Cl Me H S
4-Cl 4-Cl Me H S
4-Br 4-Cl Me H S

. ~ , : ' ' 1 ':

7~0 ~1 R2 R~ Rlo 4-OCF2~ 4-Cl Me H S
4-OCF3 4-Cl Me ~ S
4-CF3 5-F Me ~ S
4-C1 5-F Me H S
4-9r 5-F Me H S
4-OCF2H 5-F. Me H S
4-CF3 5-Cl Me H S
4-C1 5-Cl Me H S
4-Br 5-Cl Me H S
4-OCFzH 5-Cl Me H S
4-CF3 4-F Me 4-F S
4-C1 4-F Me 4-F S
4-Br 4-F Me 4-F S
4-OCF2H 4-F Me 4-F S
4-CF3 4-Cl Me 4-F S
4-C1 4-Cl Me 4-F S
: 4-3r 4-Cl Me 4-F S
; 4-OCF2H 4-Cl Me 4-F S
4-CF3 5-F Me 4-F S
4-C1 5-F Me 4-F
~-Br 5-F Me 4-F S
4-OCF2H 5-F M~ 4-F S
4-CF3 5-Cl Me 4-F S
4-C1 5-Cl Me 4-F S
4-~r 5-Cl Me 4-F S
4-OCF2~ 5-Cl Me 4-F S
4-CF3 4-F Me 4-Cl S
4-C1 4-F Me 4-Cl S
4-Br 4-F Me 4-Cl S
4-OCF2H 4-F Me 4-Cl S
4-CF3 4-Cl Me 4-Cl S
:

.

21~'7~

Rl ~ ~ Rlo A

4-C1 4-Cl Me 4-Cl S
4-Br 4-Cl Me 4-Cl S
4-OCF2H 4 Cl Me 4-Cl S
4-CF3 5-F Me 4-Cl S
4-C1 5-F Me 4-Cl S
4-Br 5-F Me 4-Cl S
4-OCF2H 5-F Me 4-Cl S
4-CF3 5-Cl Me 4-Cl S
4-C1 5-Cl Me 4-Cl S
4-Br 5-Cl Me 4-Cl S
4-OCF2H 5-Cl Me 4-Cl S
4-CF3 S-Cl M~ 4-Cl S
4-Cl S-Cl Me 4-Cl S
4-Br 5-Cl Me 4-Cl S
4-OCF2H 5-Cl Me 4-Cl S
4-CF3 5-Cl Et 4-F S
4-C1 5-Cl Et 4-F S
4-Br 5-Cl Et 4-F S
4-CF3 5-Cl Et 4-Cl S
4-C1 5-Cl Et 4-Cl S
4-~r 5-Cl Et 4-Cl S
4-CF3 5-Cl allyl 4-F S
4-C1 5-Cl allyl 4-F S
4-~r 5-Cl allyl 4-F S
4-CF3 5-Cl allyl 4-Cl S
~-Cl S-Cl allyl 4-Cl S
4-Br 5-Cl allyl 4-Cl S
4-CF3 S-Cl propargyl 4-F S
4-C1 5-Cl propargyl 4-F S
4-Br 5-Cl propargyl 4-F S
4-CF3 5-Cl propargyl 4-Cl S
4-C1 5-Cl propargyl 4-Cl S
4-Br 5-Cl propargyl 4-Cl S

'~ :

Rl R2` ~ Rlo ~ , 9-Cl H H H C~2CH2 4-OCF3 H H H CH2C~2 4-Cl 4-F H H CE.12CH2 4-Br 4-F H H CH2C~2 3,4-di-C1 4-F H H C~2CH2 4-CN 4-Cl H H CH2C~2 4-CO2Me 4-Cl H H CH2CH2 4-C1 4-Cl H H CH2CH2 4-Br 4-Cl H - H CH2C~2 4-CF3 4-Cl H H CH2CH2 4-OCF2H 4-Cl H El CH2CH2 4-OCF3 4-Cl H E} CH2CH2 4-OCF2H 5-F H H CH2C~2 4-CN 5-F H }I CH2CH2 3,4-CF2CF20 5-FH El C~2CH2 3,4-CH2C(Me)20 5-F H H C~2CH2 4-F 5-Cl El H CH2CH2 4-OCF2H 5-Cl H H CH2CH2 4-OCF3 5-Cl H H CH2CH2 4-NO2 5-Cl H H CH2CH2 4-SCF2H 5-Cl H H CH2CH2 4-CN 5-Cl H H CH2CH2 3,4-CF2CF20 5-Cl H H CH2CH2 : 35 3,4-CH2C(Me)20 5-Cl H H CH2CH2 4-C1 5-E3r H H CH2~2 ; ~ ; ' ,, ` ' 2~S7~

-1 ~2 ~ ~10 4-Br 5-8r H ~ CH2CH2 4-CF3 5-Br H H CH~CH2 4-OCF2H 5-Br H H C~2C~2 4-OCF3 5-Br H H CHZcH2 4-Br 5-CN H H CH2CH~
4-CF3 5-CN ~ ~ C~2CH2 4-OCF2H 5-CN ~ H CH2CH2 4-C1 5-OMe H ~ CH2CH2 4-Br 5-OMe H H CH2CH2 4-CF3 5-OMe H H CH2CH2 4-CF3 5-OCF2H H H CH2C~2 4-C1 5-OCF2H H H CH2C~2 4-Br 5-OCF2H H H CH2CH2 4-C1 5-OCF3 H H ~H2C~2 4-Br 5-OCF3 H H CH2CH2 4-OCF2H 5-OPh H H CH2CH2 4-OCF3 5-OPh H H CH2C~2 4-CF3 5-OPh H H CH2CH2 4-C1 5-OPh H H CH2CH2 4-Br 5-OPh H H C~2CH2 4-CF3 5-SMe H H CH2CH2 4-C1 5-SMe H H CHzCH2 4-Br 5-SMe H H CH2CH2 4-CF3 6-F H H C~2C~2 4-C1 6-F H H C~2CH2 4-Br 6-F H H CH2CH2 '~
. ~ , ~, .

2~7~

-1 ~ R~ R~Q A

q-CF3 6-Cl H H CHzc~2 4-C1 6-Cl H H CH2C~2 4-Br 6-Cl H H CH2CHz 4-C1 5-F H ~-F ~H2C~z 4-Br 5-F H 4-F CH2C~2 4-CF3 5-F ~ 4-F CH2CH2 4-OCF3 5-F H 4-F CH2C~2 3,4-di-Cl S-F H 4-F CH2CH2 3,4-CF2CF20 5-F H 4-F CHzCH2 3,4-CH2C~Me)20 5-F H 4-F CH2CH2 4-C1 5-F H 4-Cl CH2CH~
4-Br 5-F H 4-Cl CH2CH2 4-CF3 5-F H 4-Cl CH2C~2 4-OCF2H 5-F H 4-Cl CH2CH2 2~ 4-OCF3 5-F H 4-Cl CH2CH2 4-C1 5-F H 4-NO2 CH2C~2 4-Br 5-F H 4-NO2 CH2CH2 4-CF3 5-F H 4-No2 CH2CH2 4-OCF2H 5-F H 4-NOz CH2CH2 : 25 4-OCF3 5-F H 4-NO2 CH2CHz 4-C1 5-F H 4-CN C~2CH2 4-Br 5-F H 4-CN CH2CH2 4-Br 5-F H 4-CF3 CH2CH2 4-CF3 5-F H 4-OCF2H C~2CH2 4-C1 5~F H 4-OCF2H CH~CH2 ~)57~

6~

~ R2 B4 ~lQ
4-Br 5-F H 4-OCF2H CH2CH2 4-OCF3 5-F H 4~0CF2HCH2CH2 4-CF3 5-Cl H 4-F CH2CH2 4-Cl S-Cl H 4-F CH2CH2 4-8r 5-Cl ~ H 4-F CH2CH2 4-F 5-Cl H 4-F CH2CH2 4-OCF3 5-Cl H 4-F CH2C~2 4-OCF2H 5-Cl H 4-F CH2CH2 4-N2 5-Cl H 4-F CH2CH2 3,4-di-Cl 5-Cl H 4-F CH2CH2 3,4-CH2C(Me)20 5-Cl H 4-F CH2CH2 : 3.4-CF2CF20 5-Cl H 4-F CH2CH2 4-CF3 5-Cl H 4-Cl CH2CH2 4-C1 5-Cl H g-Cl CH2CH2 4-Br 5-Cl H 4-Cl CH2CH2 4-OCF3 5-Cl H 4-Cl CH2C~2 4-OCF2H 5-Cl H 4-Cl CH2CH2 3,4-CF2CF20 5-Cl H 4-Cl CH2CH2 3,4-CB2CtMe)20 5-Cl H 4-Cl CH2CH2 4-CN 5-Cl H 4-Cl CH2CH2 4-F 5-Cl H 4-Cl CH2CH2 : 4-NO2 5-Cl H 4-Cl CH~CH2 : H 5-Cl H 4-Cl ~H2C~2 ~: 4 C1 5-CF3 H 4-F CH2CH2 4-Br 5-CF3 H 4-F CH2CH2 4-CF3. 5-OCF2H H 4-F CH2CH2 4-C1 5-OCF2H H 4-F CH2~H2 4-Br 5-OCF2H H 4-F CH2CH2 4-CF3 5-OCF2H H 4-Cl C~2C~2 -: ; ` '~ ' :' ' '' ' : ' :: : :,.: . :

5~

~ ~ ~10 4-C1 5-OCF~8 H 4-Cl tH~CH2 4-Br 5-OCF2H H 4-Cl CH2CH2 4-Cl 4-F H 4-F CH2CH2 4-Br 4-F H 4-F CH2C~2 4-CE'3 4-F H . 4-Cl ~H2CH2 4-C1 4-F H 4-Cl CH2CH2 4-Br 4-F H 4-Cl CH2CH2 4-CF3 4-Cl H 4-Cl CH2CX2 4-C1 4-Cl H 4-Cl CH2CH2 4-Br 4-Cl H 4-Cl CH2CH2 4-CF3 4-Cl H 4-F CH2CH2 4 Cl 4-Cl H 4-F CH2CH2 4-Br 4-Cl H 4-F CH2CH2 4-CF3 5-Cl H q-cF3 CH2CH2 4-C1 5-Cl H 4-CF~ CH2CH2 4-Br 5-Cl H 4-CF~ CH2CH2 4-OCF2H 5-Cl H 4-CF~ CH2CH2 4-CF3 5-Cl H 4-Me CH2CH2 4-C1 5-Cl H 4-Me CH2CH2 4-Br 5-Cl H 4-Me CH2CH2 4-OCF2H 5-Cl H 4-Me CH2CH2 4-CF3 5-Cl H 4-SM~ CH2CH2 4-C1 5-Cl H 4-SMe CH2CH2 4-~3r 5-Cl H 4-SMe CH2CH2 4-OCF3 5-Cl H 4-SMe CH2CH2 4-CP3 5-Cl H 4-N02 CH2C~2 4-C1 5-Cl H 4-N02 CH2CH2 4-Br 5-Cl H 4-N02 CH2CH2 4-OCF2H 5-Cl H 4-N02 CH2CH2 4-CF3 5-Cl H 4-OPh CH2CH2 4-C1 5-Cl H 4-OPh C~2C~2 4-Br 5-Cl H 4-OPh C~2CH2 '~ . ' '' ~ ' ` ' .

2C3~7~

--1 ~ ~ --lQ A
4-OCF2H S-Cl H 4 OPh ~H2CH2 4-CF3 H Me H C~2CH2 4-Cl H Me H CHzCH2 4-Br H Me H C~2CR2 4-OCF2H H Me H CH2CB2 4-OCF3 H Me H CH2CH2 4-CF3 4-F Me H CH2C~2 4-C1 4-F Me H CH2CH2 4-Br 4-F Me H CH2CB2 4-OCF2.H 4-F Me H C~2C~2 4 OCF3 4-F Me H CH2CH2 4-CF3 4-Cl Me B CH2CH2 4-C1 4-Cl Me B CH2CHz 4-Br 4-Cl Me H CH2CH2 4-OCF2H 4-Cl Me H CH2CH2 : 20 4-OCF3 4-Cl Me H CU2CH2 4-CF3 5-F Me H CH2CH2 4-C1 5-F Me H CH2CH2 4-Br 5-F Me H CH2CH2 4-OCF2H 5-F Me H CH2CH2 : 25 4-CF3 5-Cl Me H CH2CH2 . 4-C1 5-Cl Me H CH2CH2 4-Br 5-Cl Me H CH2CH2 4-OCF2H 5-Cl Me H CH2CH2 ~` 4-CF~ 4-F Me 4-~ CH2C~2 4-C1 4-F Me 4-F CH2CH2 4-8r 4-F Me 4-F CH2CH2 4-OCF2H 4-F Me 4-F CH2CH2 4-CF3 4-Cl Me 4-F CH2CH2 4-Cl 4-Cl Me 4-F CH2CH2 4-Br 4-Cl Me 4-F CHzCH2 4-OCF2H 4-Cl Me 4-F C~2CH2 : 4-CF3 5-F Me 4-F CH2CH2 . 4-C1 5-F Me 4-F C~2CH2 - , :; , ~ ~ , , :

, 2~ 7~

Rl R2 R4 Rlo A

4-~r 5-F Me 4-F CH2CH2 4-OCF2H 5-F Me 4-F CH2CH2 4-CF3 5-Cl Me 4-F CH2C~2 4-C1 5-Cl Me 4-F CH2CH~
4-Br 5-Cl Me 4-F C~2CH2 4-OCF2H 5-Cl Me 4-F CH2CH2 4-CF3 4-F Me 4-Cl C~2CH2 4-C1 4-F Me 4-Cl CH2CH2 4-Br 4-F Me 4-Cl CH2CH2 4-OCF2H 4-F Me 4-Cl CH2CH2 4-CF3 4-Cl Me 4-Cl CH2CH2 4-C1 4-Cl Me 4-Cl CH2CH2 4-Br 4-Cl Me 4-Cl CH2CH2 4-OCF2H 4-Cl Me 4-Cl CH2CH2 4-CF3 5-F Me 4-Cl CH2CH2 ~0 4-C1 5-F Me 4-Cl CH2CH2 4-3r 5-F Me 4-Cl Lil2CH2 4-OCF2H 5-F Me 4-Cl CH2CH2 4-CF3 5-Cl Me 4-Cl CH2CH2 4-C1 5-Cl Me 4-Cl CH2CH2 4-Br 5-Cl Me 4-Cl CH2C~2 4-OCF2B 5-Cl Me 4-Cl CH2CH2 4-CF3 5-Cl Me 4-Cl CH2CH2 4-C1 5-Cl Me 4-Cl CH2CH2 4-Br 5-Cl Me 4-Cl CH2CH2 4-OCF2H 5-Cl Me 4-Cl C~l2CH2 4-CF3 5-Cl Et 4-F CH2CHz 4-C1 5-Cl Et 4-F CH2C~2 4-~r 5-Cl Et q-F CH2CH2 4-CF3 5-Cl Et 4-Cl CH2CH2 4-C1 5-Cl Et 4-Cl CH2CH2 4-Br 5-Cl Et 4-Cl C~2C~2 4-CF3 5-Cl allyl 4-F CH2CH2 O

Rl ~ ~ ~lQ A

4-C1 5-Cl allyl 4-F CH2CH2 4-Br 5-Cl allyl 4-F C~2CH2 4-CF3 5-Cl allyl 4-Cl C~2CH2 4-C1 5-Cl allyl 4-Cl C~2CH2 4-Br 5-Cl allyl 4-Cl CH2CH2 4-CF3 5-Cl propargyl 4-F CH2CH2 4-C1 5-Cl propargyl 4-F CH2CH2 4-Br 5-Cl propargyl 4-F ~H2CH2 4-CF3 5-Cl propargyl 4-Cl CH2CH2 4-C1 5-Cl propargyl 4-Cl C~2CH2 4-Br S-Cl propargyl 4-Cl CH2CH2 4-CF3 5-F H 4-F NMe 4-OCF3 5-F H 4-F NMe 4-CF3 5-Cl H 4-F NNe 4-OCF3 5-Cl H 4-F NMe 4-CF3 4-F Me 4-Cl NMe 4-C1 4-F Me 4-Cl NMe 4-Br 4-F Me 4-Cl NMe 4-OCF2H 4-F Me 4-Cl NMe 4-CF3 4-Cl Me 4-Cl NMe 4-C1 4-Cl Me 4-Cl NMe 4-Br 4-Cl Me 4-Cl ~Me 4-OCF2H 4-Cl Me 4-Cl NMe 4-CF3 5-F Me 4-Cl NMe 4-C1 5-F Me 4-Cl NMe 4-Br 5-F Me 4-Cl NMe 4-OCF2H 5-F Me 4-Cl Nh~e 4-CF3 5-Cl Me 4-Cl NMe 4-C1 5-Cl Me 4-Cl NMe 4-Br 5-Cl Me 4-Cl NMe 4-OCF2H 5-Cl Me 4-Cl NMe 4-CF3 5-Cl Me 4-Cl NMe ' " ~

5~

R2 R4 ~10 A

~-Cl S-Cl Me 4-Cl NMe 4-Br 5-Cl Me 4-Cl NMe 4-OCF2H 5-Cl Me 4 Cl NMe 4-F 5-F H H CEMe 4-C1 5-F H H CHMe 4-Br 5-F H H CHMe 4-CF3 5-F H H CHMe 4-OCF2H 5-F H H CHMe 4-OCF3 5-F H H CHMe 4-NO2 5-F H H CHMe 4-SCF2H 5-F H H CHMe 4-CN 5-F H H CHMe 3,4-CF2CF2o 5-F H H CHMe 3,4-CH2C(Me)20 S-F H H CHMe 4-F 5-Cl H H CHMe 4-C1 5-Cl H H CHMe 4-13r 5-Cl H H CHMe 4-CF3 5-Cl H H CHMe 4-OCF2H S-Cl H H CHMe 4-OCF3 5-Cl H H CHMe 4-NO2 5-Cl H H CHMe 4-CF3 4-Cl H 4-Cl CHMe 4-C1 4-Cl H 4-Cl CHMe 4-Br 4-Cl H 4-Cl CHMe 4-CF3 4-Cl H 4-F CHMe 4-C1 4-Cl H 4-F CHMe 4-~r 4-C1 H 4-F CHMe . 4-CF3 5-Cl H 4-CF3 CHMe 4-Cl S-Cl H 4-CF3 CHMe 4-Br 5-C1 8 4-CF3 CHMe 4~0CF2H 5-Cl H 4-CF3 CHMe 4-CF3 5-Cl H 4-Me CHMe 4-C1 5-C1 H 4-Me CHMe ~S~

-1 R2 R4 -lQ A

4-Br 5-Cl H 4-Me CHMe 4-OCF2H 5-Cl H 4-Me CHMe 4-CF3 5-Cl H 4-SMe CHMe 4-C1 5-C1 H 4-SMe CHMe 4-Br 5-Cl H 4-SMe CBMe 4-OCF2H 5-Cl B 4-SMe CHMe 4-CF3 4-F Me 4-Cl CEMe 4-C1 4-F Me 4-Cl CHMe 4-Br 4-F Me 4~Cl CHMe 4-OCF2H 4-F Me 4-Cl CHMe 4-CF3 4-Cl Me 4-Cl CBMe 4-C1 4-Cl Me 4-Cl CHMe 4-Br 4-Cl Me 4-Cl CHMe 4-OCF2H 4-Cl Me 4-Cl CHMe 4-CF3 5-F Me 4-Cl CHMe 4-C1 5-F Me 4-Cl CHMe 4-Br 5-F Me 4-Cl CHMe 4-OCF2H 5-F Me 4-Cl CHMe 4-CF3 5-Cl Me 4-Cl CBMe 4-C1 5-Cl Me 4-Cl CHMe 4-Br 5-Cl Me 4-Cl CHMe 4-OCF2H 5-Cl Me 4-Cl CHMe 4-CF3 5-Cl Me 4-Cl CHMe 4-C1 5-Cl Me 4-Cl CHMe 4-Br 5-Cl Me 4-Cl CHMe 4-OCF2H 5-Cl Me 4-Cl C~Me 4-CF3 4-F Me 4-Cl S02 4-C1 4-F Me 4-Cl S02 4-Br 4-F Me 4~Cl S02 4-OCF2H 4-F Me 4-C1 52 4-CF3 4-Cl Me 4-Cl S02 4-C1 4-Cl Me 4-C1 52 2~5~

~1 R2 ~ BLQ A

4-8r 4-Cl Me 4-Cl S02 4-OCFzH 4-Cl Me 4-Cl S02 4-CF3 5-F Me 4-Cl SO2 4-C1 5-F Me 4-C1 52 4-Br 5-F Me 4-Cl SO2 4-OCF2H 5-F Me 4-Cl SO2 4-CF3 5-Cl Me 4-Cl SO2 4 Cl 5-Cl Me 4-Cl SO2 4-Br ~-Cl Me 4-Cl SO2 4 -OCF2H 5-Cl Me 4-Cl SO 2 4-CF3 5-Cl Me 4-Cl SO2 4-C1 5-Cl Me 4-Cl SO2 4-Br 5-Cl Me 4-Cl SO2 4-OCF2H 5-Cl Me 4-Cl SO2 4-F 5-F H H C(Me)2 4-C1 5-F H H C(Me)2 4-Br 5-F H H C(Me)2 4-CF3 5-F H H C (Me)2 4-OCF2H 5-F H H C (Me ) 2 4-OCF3 S F H H C(Me)2 : 25 4-N2 5-F H H C (Me ) 2 4-SCF2H 5-F H H C(Me)~
4 -CN 5-F H H C (Me ) 2 3,4-CF2CF2O 5-F H H C(Me)2 3,4-CH2C(Me)20 5-F H H C(Me)2 4-F 5-Cl H H C (Me)2 4-C1 5-Cl H H CtMe)2 4-Br 5~Cl H H C tMe ) 2 4-CF3 5-Cl H H C(Me)2 4-OCF2H 5-Cl H H C(Me)2 4 -OCF3 5-Cl H H C(Me)2 X~)57~

Rl 2 4 -lQ A

4-NO2 5-Cl H H C(Me)2 4-CF3 4-Cl H 4-Cl C(Me)2 4-C1 4-Cl H 4-Cl CtMe)2 4-Br 4-Cl H 4-Cl C(Me)2 4-CF3 4-Cl H 4-F C(M~)2 4-C1 4-Cl H 4-F C(Me)2 4-Br 4-Cl H 4-F C(Me)2 4-OCF3 4-Cl H 4-F C(Me)2 4-CF3 5-C' H 4-CF3 C(Me)2 4-C1 5-Cl H 4-CF3 C(Me)2 4-Br 5-C1 H 4-CF3 C(Me)2 4-OCF2H 5-Cl H 4-CF3 C(Me)2 4-OCF3 5-Cl H 4-CF3 C(Me)2 4-CF3 5-Cl H 4-Me C(Me)2 4-C1 5-Cl H 4-Me C(Me)2 4-Br 5-Cl H 4-Me C(Me)2 4-OCF2H 5-Cl H 4-Me C(Me)2 4-CF3 5-F Me 4-F C(Me)2 g-Cl 5-F Me 4-F C(Me)2 4-Br 5-F Me 4-F C(Me)2 4-OCF3 5-F Me 4-F C(Me)2 4-OCF2H 5-F Me 4-F C(Me)2 4-CF3 5-Cl H 4-SMe C(Me)2 4-C1 5-Cl H 4-SMe C(Me)2 4-Br 5-Cl H 4-SMe C(Me)2 4-OCF2H 5-Cl H 4-SMe C(Me)2 4-CF3 4-F Me 4-Cl C~Me)2 4-C1 4-F Me 4-Cl C(Me)~
4-~r 4-F Me 4-Cl ~ C(Me)2 4-OCF2H 4-F Me 4-Cl C(Me)2 4-CF3 4-Cl Me 4-Cl C(Me)2 4-C1 4-Cl Me 4-Cl C(Me)2 4-8r 4-Cl Me 4-Cl C(Me)2 , . ..

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4-OCF2H 4-Cl Me 4-Cl C(Me)2 4-CF3 S-F Me 4-Cl C(Me)2 4-C1 5-F Me 4-Cl C(Me)2 4-Br 5-F Me 4-Cl C(Me)2 4-OCF2H 5-F Me 4-Cl ~(Me)2 4-CF3 5-Cl Me 4-Cl C(Me)2 4-Cl S-Cl Me 4-Cl C(Me)2 4-Br 5-Cl Me 4-Cl C(Me)2 4-OCF2H S-Cl Me 4-Cl C(Me~2 4-CF3 5-Cl Me 4-Cl C(Me)2 4-C1 5-Cl Me 4-Cl C(Me)2 4-Br 5-Cl Me 4-Cl C(Me)2 4-OCF2H 5-Cl Me 4-Cl C(Me)2 4-CF3 5-F Me 4-F C(Me)2 4-OCF3 5-F Me 4-F C(Me)2 4-CF3 4-Cl Me 4-Cl S(O) 4-C1 4-Cl Me 4-Cl S(O) 4-~r 4-Cl Me 4-Cl S~O) 4-OCF2H 4-Cl Me 4-Cl S(O) 4-CF S-F Me 4-Cl S(O) 3 ~
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4-C1 5-F Me 4-Cl OCH2 4-Br 5-F Me 4-Cl OCH~
4-OCF~H 5-F Me 4-Cl OCH2 4-CF3 S-Cl Me 4-Cl OCH2 4-Cl S-Cl Me 4-Cl OCH2 4-Br 5-Cl Me 4-Cl OCH2 4-OCF2H 5-Cl Me 4-Cl OCH2 4-CF3 5-Cl Me 4-Cl OCH2 4-C1 5-Cl Me 4-Cl OCH2 4-Br 5-Cl Me 4-Cl OCH2 :: : ~.-i,:.

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4-OCF2H 5-Cl Me 4-Cl OCH2 4-Br 5-F H H CH20 3,4-CFzCF20 5-F H H CH20 3,4-CH2C(Me)20 5-F H H CH20 4-CF3 4-Cl H 4-Cl CH20 4-C1 4-Cl H 4-Cl CH20 4-Br 4-Cl H 4-Cl CH20 4-C1 4-Cl H 4-F CH20 4-Br 4-Cl H 4-F CH20 4-CF3 5-Cl H 4 CF3 CH20 4-C1 5-Cl H 4-CF3 CH20 4-Br 5-Cl H 4-CF3 CH2 4-OCF2H 5-Cl H 4-CF3 CH20 4-CF3 4-F Me 4-Cl CH20 4-C1 4-F Me 4-Cl CH20 4-Br 4-F Me 9-Cl CH20 4-OCF2H 4-~ Me 4-Cl C~2 4-CF3 4-Cl Me 4-Cl CH20 4-C1 4-Cl Me 4-Cl CH20 4-Br 4-Cl Me 4-Cl CH20 4-OCF2H 4-Cl Me 4-Cl CH20 4-CF3 5-F Me 4-Cl CH20 4-C1 5-F Me 4-Cl CH20 4-Br 5-F Me 4-Cl CH20 :: .
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7~

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g-ocF2H S-Cl Me 4-Cl CH2O
4-CF3 5-Cl Me 4-Cl CH2O
4-C1 5-Cl ~e 4-Cl CH2O
4-Br S-Cl Me 4-Cl CH2O
4-OCF2H 5-Cl Me 4-Cl CH2O

4-Br 5-F H H SCH2 4-Cl S-Cl H H SCH2 4-Br 5-Cl H H SCH2 4-CF3 5-Cl H H SCH2 4-OCF2H 5-Cl H H SCH2 4-OCF3 5-Cl H H SCH2 4-CF3 4-Cl H 4-Cl SCH2 4-C1 4-C1 H 4-Cl SCH2 4-Br 4-Cl H 4-Cl SCH2 4-CF3 4-Cl H 4-F SCH2 4-C1 4-Cl H 4-F SCH2 4-Br 4-Cl H 4-F SCH2 4-CF3 5-Cl H 4-CF3 SCH2 4-C1 5-Cl H g-CF3 SCH2 4-Br 5-Cl H 9-CF3 SCH2 4-OCF2H 5-Cl H 4-CF3 SCH2 4-CF3 4-F Me 4-Cl SCH2 4-C1 4-F Me 4-Cl SCH2 4-Br 4-F Me 4-Cl SCH2 :. .~ . . . -.;
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4-CF3 4-F H 4-Cl CH2S
4-C1 4-F H 4-Cl CH2S
4-Br 4-F H 4-Cl CH2S
4-CF3 . 5-F H 4-F CH2S
4-C1 5-F H 4-F CH~S
4-8r 5-F H 4-F CH2S

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97~

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4-C1 5-F Me Me CH2 4-Br 5-F Me Me CH2 4-CF3 5-OCF2H Me Me CH2 4-C1 5-OCF2H Me Me CH2 4-Br 5-OCF2H Me Me CH2 4-CF3 5-OCF3 Me Me CH2 4-C1 5-OCF3 Me M~ CH2 4-8r 5-OCF3 Me Me CH2 : 4-CF3 4-F Me Me CH2 4-C1 4-F Me Me CH2 4-Br 4-F Me Me CH2 4-CF3 5-Br Me Me CH2 4-C1 5-Br Me Me CH2 4-Br 5-Br Me Me CH2 4-CF3 5-Cl CH2Ph H CH2 ", ~

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4-OCF2H 5-F CO2Me Me CH2 4-OCF3 5-F CO2Me Me CH2 3,4-CF2CF20 5-F CO2Me Me CH2 3,4-CH2C(Me)20 5-F C2M~ Me C~2 4-CF3 4-F C2Me Me C~2 4-C1 4-F CO~Me Me CH2 4-Br 4-F CO~Me Me CH2 4-OCF3 4-F CO2M~ Me CH2 4-OCF2H 4-F CO2Me Ms CH2 3,4-CF2CF20 4-F CO2Me Me C~2 ' ~" ' ~ .' ` I ''~;

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3,4-CH2C(Me)20 5-OCF3 CO2Me Me CH2 4-CF3 5-CN C02Me Me CH2 4-Cl S-CN C02Me Me C~2 4-Br 5-CN CO2Me Me CH2 4-OCF2H 5-CN CO2Me Me CH2 .

. , Rl R2 ~ R4 4-OCF3 5-CN CO2Me Me CH2 4-CF3 5-CF3 C02Me Me CH2 4-OCF3 5-CF3 C2M~ Me CH2 4-CF3 6-F C02Me Me C~2 4-C1 6-F CO2Me Me CH2 4-Br 6-F CO2Me Me CH2 4-OCF2H 6-F CO2Me Me CH2 4-OCF3 6-F CO2Me Me C~2 4-CF3 5-Cl CO2Me Et CH2 4-C1 5-Cl CO2Me Et CH2 4-Br 5-Cl CO2Me Et CH2 4-CF3 5-Cl CO2Me CH2Ph CH2 4-C1 5-Cl CO2Me CH2Ph C~2 4-8r 5-Cl CO2Me CH2Ph CH2 4-CF3 5-Cl CO~Me allyl CH2 4-C1 5-Cl CO2Me allyl C~2 4-Br S-Cl CO2Me allyl CH2 4-CF3 5-F CO2Et Me CH2 4-C1 5-F C2Et Me CH2 4-Br 5-F C2~t Me CH2 4-CF3 5-F CO2CH2CF3 Me CH2 4-C1 5-F CO2CH2CF3 Me C~2 4-Br 5-FCO2CH2CF3 Me CH2 ~-CF3 5-F C02Ph Me CH2 4-C1 5-F C02Ph Me C~2 4-Br 5-F C02Ph Me CH2 4-CF3 5-Cl co2~ H CH2 4-CF3 5-Cl CONHMe H CH2 4-CF3 5-Cl CONMe H CH2 4-CF3 5-Cl CONHPh H CH2 4-CF3 5-Cl CSNMe2 H CH2 4-CF3 5-Cl pr~parqyl Me CH2 4-CF3 5-Cl CH2CH2CN Me CH2 '.~: ' .
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go 4-CF3 6-Cl H H CH2CH2 4-C1 6-Cl B H CH2CH2 4-Br 6-Cl H 8 CB2CH2 4-OCF2H 6 Cl B H CH2CH2 4-CF3 4-F Me H CH2CH2 4-C1 4-F Me H CH2CH2 4-Br 4-F Me H CH2CH2 4-OCF2H 4-F Me H CH2CH2 ~-CF3 5-Cl Me ~ CB2C~2 4-Cl S-Cl Me ~ C~2CH2 4-Br S-Cl Me H CH2CH2 4-OCF2H 5-Cl Me H CH2CH2 4-CF3 5-OCF2H Me B CH2CH2 4-C1 5-OCF2H Me H CH2CH2 4-Br 5-OCF2H Me H CH2C~2 4-OCF2H 5-OCF2H Me H CH2C82 4-CF3 5-F Me H CHzCB2 4-C1 5-F Me H CH2CH2 4-Br 5-F Me H CB2C~2 4-CF3 S-Cl Ft H CH2C~12 4-C1 5-Cl Et H CB2CH2 4-Br 5-Cl Et H CH2CH2 4-CF3 5-OCF2H Et H CH2C~2 4-C1 5-OCF2H Et ~ CH2CH2 4-Br 5-OCF2H ~t H CH2CH2 4-CF3 5-F n-Bu H C~2CH2 4-C1 5-F n-Bu H CH2CH2 4-~r 5-F n-Bu H CH2C82 4-CF3 4-F n-8u H CH2CH2 4-C1 4-F n-Bu B ~ CH2CH2 4-8r 4-F n-Bu H CH2CH2 4-CF3 5-Cl allyl H C~2CH2 4-C1 5-Cl allyl H CH2CH2 : : ~ :'~

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7~q~

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4-OCF2H 5-OCF2H CH2Ph-4-F H CH2CH2 4-CF3 5-Cl CH2Ph-4-Cl H CH2CH2 4-C1 5-Cl CH2Ph-4-Cl H C~2CH2 4-Br 5-Cl CH2Ph-4-Cl H CH2C~2 4-OCF3 5-Cl CH2Ph~4-Cl H CH2CH2 4-OCF2H 5-Cl CH2Ph-4-Cl ~ CH;2CH2 4-CF3 H CO2Me H CH2CH2 4-Cl H CO2Me H CH2CH2 4-Br H CO2Me ~ CH2CH2 4-OCF2H H C02Me H CH2CH2 4-F H CO2Me ~ CH2CH2 4-CF3 5-Cl CO2Me H C~2CH2 4-C1 5-Cl CO2Me B CH2CH2 4-Br 5-Cl CO2Me H CH2CH2 4-OCF2H 5-Cl CO2Me H CH2CH2 ~0 4-OCF3 5-Cl CO2Me ~ CH2CH2 4-NO2 5-Cl C02Me H CH2CH2 4-CF3 5-F CO,2Me H CH2CH2 4-C1 5-F C2Me H CH2CH2 4-Br 5-F C2Me H CH2CH2 4-OCF2H 5-F C02Me H C~2CH2 ` 4-OCF3 5-F CO2Me H CH2CH2 4-CN 5-F C02Me H CH2CH2 4-CF3 4-F CO2Me H CH2CH2 4-C1 4-F CO2Me ~ CH2CH2 3G 4-Br 4-F C2Me H CH2CH2 4-CF3 ~-Cl C02Me H CH2CH2 q-Cl 4-Cl C02Me H CH2CH2 4-Br 4-Cl CO2Me H CH2CH2 4-CF3 5-Cl C02Me Me ~2CH2 4-C1 5-Cl CO2Me Me CH2CH2 4-Br 5-Cl C2Me Me C~2CH2 4-OCF2H 5-Cl CO2Me Me CH~CH2 ~.,;

.' ~ ` :' 2~ 7~

~ R2 ~ R4 A

4-OCF3 5-Cl CO2Me Me CH2C~2 3,4-CF2CF2O 5-Cl CO2Me Me C~2CH2 3,4-CF2C(Me)2O 5-Cl CO2Me Me CH2CH2 ~-CF3 5-F CO2Me Me CH2CH2 4-C1 5-F CO2Me Me CH2CH2 4-Br 5-F CO2Me Me CH2C~2 4-OCF2H 5-F CO2Me Me CH2CH2 4-OCF3 5-F CO2Me Me CH2CH2 3,4-CF2CF2O 5-F CO2Me Me CH2CH2 3,4-CH2C(Me)2O 5-F CO2Me Me CH2CH2 4-Cl H H H O
4-Br H H H O

4-OCF~H H H H O

4-C1 4-F H }I O
4-Br 4-F H H O

4-CF3 ~-Cl H H O
4 Cl 4-Cl H H O
4-Br 4-Cl H H O
4-OCF3 4-Cl H H O
4-OCF2H 4-Cl H H O
4-CF3 5-F }I H O

4-Br 5-F H H O

4-CF3 4-F Me H O
4-C1 4-F Me H O

57~

~ 2 B~ ~ A

4-Br 4-F Me H O
4-OCF3 4-F Me H O
4-OCF2H 4-F Me H O
4-CF3 5-Cl Me H O
4-C1 5-Cl Me H O
4-8r 5-Cl Me H O
4-OCF3 5-Cl Me H O
4-OCF2H 5-Cl Me H O
4-CF3 5-OCF2H Me H O
4-C1 5-OCF2H Me H O
4-Br 5-OCF2H Me H O
4-OCF3 5-OCF2H Me H O
4-OCF2H 5-OCF2H Me H O
4-CF3 5-CF3 Me H O
4-C1 5-CF3 Me H O
4-ar 5-CF3 Me H O
4-OCF3 5-CF3 Me H O
4-OCF2H 5-CF3 Me H O
4-CF3 5-F Me H O
4-C1 5-F Me H O
4-ar 5-F Me H O
4-OCF3 5-F Me H O
4-CF3 5-Cl Et H O
4-C1 5-Cl Et H O
4-Br 5-Cl Et H O
4-CF3 5-OCF2H Et H O
4-C1 5-OCF2H Et H O
4-8r 5-OCF2H Et H O
4-CF3 5-F n-Bu H O
4-Cl S-F n-Bu 8 O
4-Br 5-F n-~u H O
4 CF3 4-F n-Bu H O
4-C1 4-F n-Bu H O

' , ::

`: ' ' ' .:
': :

~57~

Rl R2 ~ R

4-Br 4-F n-Bu H O
4-CF3 5-Cl allyl H O
4 Cl 5-Cl allyl H O
4-Br 5-Cl allyl H O
4-CF3 5-Cl Me M~ O
4-C1 5-Cl Me Me O
4-8r 5-Cl Me Me 4-CF3 S-F Me Me O
4-C1 5-F Me Me O
4-Br S-F Me Me O
lS 4-CF3 5-OCF2H Me Me O
4-C1 5-OCF2H Me Me O
4-Br 5-OCF2H Me Me O
4-CF3 5-OCF3 Me Me O
4-C1 5-OCF3 Me Me O
4-Br 5-OCF3 Me Me O
4-CF3 4-F Me Me O
4-C1 4-F Me Me O
4-Br 4-F Me Me O
4-CF3 5-Br Me Me O
4-C1 5-Br Me Me O
4-8r 5-Br Me Me O
4-OCF3 5-Cl allyl Me O
4-CF3 5-F allyl Me O
4-OCF3 5-F allyl Me O
4-CF3 5-F Et Me O
4-OCF3 5-F Et Me O
4-CF3 5-Cl Et Me O
4-OCF3 5-Cl Et Me O
4-CF3 5-CF3 Et Me O
4-CF3 5-CF3 allyl Me O
4-OCF3 S-CF3 allyl Me O
4-CF3 5-F CH2Ph Me O

~ ` ~

7~

Rl -R-2 ~ R4 4-OCF3 5-F CH2Ph Me O
4-CF3 5-Cl CH2Ph Me O
4-OCF3 5-Cl CH2Ph Me O
4-CF3 5-Cl CH2P~i H O
4-C1 5-Cl CH2Ph H O
4-Br S-Cl CH2Ph H O
4-OCF3 5-Cl CH2Ph H O
4-OCF2H 5-Cl CHzPh B O
4-CF3 5-F CH2Ph-4-F H O
4-C1 5-F CH2Ph-4-F H O
4-Br 5-F CH2Ph-4-F H O
4-OCF2H 5-F CH2Ph-4-F H O
4-OCF3 5-F CH2Ph-4-F H O
4-CF3 5-OCF2H CH2Ph-4-F H O
4-C1 5-OCF2H CH2Ph-4-F H O
4 Br 5-OCF2H CH2Ph-4-F H O
4-OCF3 5-OCF2H CH~!Ph-4-F H O
4-OCF2H 5-OCF2H CH;!Ph-4-F H O
4-CF3 5-Cl CH;!Ph-4-Cl H O
4-C1 5-Cl CH2Ph-4-Cl H O
4-Br 5-Cl CH2Ph-4-Cl H O
:~ 4-OCF3 5-Cl CH2Ph-4-Cl H O
4-OCF2H S-Cl CH~Ph-4-Cl H O
4-CF3 H CO2Me H O
4-Cl H CO2Me H O
4-Br H C02Me H O
4-OCF2H H C2Me H O
4-F H CO2Me H O
4-CF3 5-Cl CO2Me H O
4-C1 5-Cl CO2Me H O
4-Br 5-Cl CO2M~ H O
4-OCF2H 5-Cl CO2Me H O
4-OCF3 5-Cl C2M2 H O

; :

7~

Rl ~ ~ Bq .

4-NO2 5-Cl CQ2Me ~ O
4-CF3 5-F COzMe H O
4-C1 5-F CO2Me H O
~-Br S-F CO2Me H O
4-OCF2H S-F CO2Me H O
4-OCF3 S-F CO2Me H O
4-CN 5~F CO2Me H O
4-CF3 4-F C02Me H O
4-C1 4-F CO2Me H O
4-Br 4-F CO2Me H O
4-CF3 4-Cl C02Me H O
4-C1 4-Cl CO2Me H O
4-Br 4-Cl CO2Me H O
4-CF3 H C02Me Me O
4-Cl H CO2Me Me O
4-Br H C02Me Me 4-OCF2H H CO2Me Me O
4-OCF3 H CO2Me Me O
4-CF3 S-Cl CO2Me Me O
4-C1 5-Cl C02Me Me O
: 25 4-Br S-Cl COzMe Me O
4-OC~2H S-Cl CO2Me Me O
4-OCF3 S-Cl CO2Me Me O
4-CF3 5-F CO2Me Me O
4-C1 5-F CO2Me Me O
4-Br S F CO2Me Me O
4-OCF2H 5 F CO2Me Me O
4-OCF3 5-F CO2Me Me O
~-CF3 4-F CO2Me Me O
4-Cl 4-F CO2Me Me O
4-Br 4-F CO2Me Me O
4-OCF3 4-F CO2Me Me O
4-OCF2H 4-F CO2Me Me O

~57~

Rl ~ ~ ~ A

3,4-CF2CF20 4-F C02Me Me O
3,4-CH2C(Me)20 4-F C2~e Me O
4-CF3 5-CF3 C02Me Me O
4 Cl S-CF3 CO2Me Me O
4-8r 5-CF3 CO2Me Me O
4-OCF3 5-CF3 CO2Me Me O
4-OCF2H 5-CF3 CO2Me Ma O
4-CF3 5-Br CO2Me Me O
4-Cl S-Br CO2Me Me O
4-Br 5-Br CO2Me Me O
4-OCF3 5-Br CO2Me Me O
4-OCF2H 5-Br CXMe Me O
3,4-CF2CF20 5-Br CO2Me Me O
3~4-cH2c~Me)2o 5-Br C2Me Me O
4-CF3 5-OCF2H CXMe Me O
4-C1 5-OCF2H C02Me Me O
4-Br 5-OCF2H COxMe Me O
4-OCF3 5-OCF2H COj,Me Me O
4-OCF2H 5-OCF2H CO.;,Me Me O
4-CF3 5-Cl CO;,Me Et O
4-C1 5-Cl CO2Me Et O
4-8r 5-Cl CO2Me Et O
4-CF3 S-Cl C02Me C~2Ph O
4-C1 5-Cl C2Me CH2Ph O
4-Br 5-Cl CO2Me CH2Ph O
4-CF3 5-Cl C02Me allyl O
4-C1 5-Cl CO2Me allyl O
4-Br 5-Cl CO2Me allyl O
4-CF3 5-F C02Et Me O
4-Cl 5-F CO2Et Me O
4-Br 5-F C02Et Me O
4-CF3 5-F CO2CH2CF3 Me O
4-C1 5-F CO2CH2CF3 Me O

- . .. :
: . :. , : . :~

.
' ' ~ :

J7~iLO

Rl ~2 4-Br 5-F CO2CH2CF3 Me O
-CF3 5-F C02Ph Me O
4-C1 5-F CO2Ph Me O
4-Br 5-F CO2Ph Me O
4-CF3 5-Cl co2~ H O
4-CF3 5-Cl CONHMe H O
4-CF3 5-Cl CONMe H O
4-CF3 5-Cl CONHPh H O
~-CF3 5-Cl CSNMe2 H O
4-CF3 5-Cl propargyl Me O
4-CF3 5-Cl CH2CH2CN Me O
4-CF3 5-C1 CH2CO2Me Me O
4-CF3 5-Cl CH~OMe Me O
4-CF3 5-Cl OMe H O
4-CF3 5-Cl SMe H O
~ 4-CF3 5-Cl SO2Me H O
4-CF3 5-Cl C(O)Me Me O
4-CF3 5-Cl C(O)Et Me O
4-CF3 5-Cl C(O)Me H O
4-CF3 5-Cl C(O)Et H O
4-CF3 5-Cl CN Me O
: 4-CF3 5-Cl CN Et O
4-CF3 5-Cl CN CH2Ph O
4-CF3 5-Cl CN H O

: 30 4-Cl H H H S
4-Br H H H S

4-Cl q-F H H S
4-Br 4-F H H S

4-CF3 4-Cl H H S

: : ' :

' ' ~ ~' : "' Z~

4-C1 4-Cl H H S
4-Br 4-Cl H H S
4-OCF2H 4-Cl H H S

4-Cl 5-F H B S
0 4-Br 5-F H H S

4-CF3 4-F Me H S
4-Cl 4-F Me H S
4-Br 4-F Me H S
4-OCF2H 4-F Me H S
4-CF3 5-Cl Me ~ S
4-C1 5-Cl Me H S
4-Br S-Cl Me H S
4-OCF2H 5-Cl Me H S
4-CF3 5-OCF2H Me H S
4-C1 5-OCF2H Me H S
4-Br 5-OCF2H Me H S
4-OCF2H 5-OCF2H Me H S
4-CF3 S-F Me H S
4-Cl S-F Me H S
4-Br 5-F Me ~ S
4-CF3 5-Cl Et H S
4-C1 5-Cl Et H S
4-Br 5-Cl Et H S
4-CF3 5-OCF2H Et H S
4-C1 5-OCF2H Et H S
4-Br 5-OCF2H Et H S
4-CF3 5-F n-Bu H S
4-C1 5-F n- u H S
4-Br 5-F n-Bu H S
4-CF3 4-F n-Bu H S
4-C1 4-F n-Bu H S

' . :' .: ; .
. . .

Rl ~ ~3 ~4 A

4-Br 4-F n-Bu H S
4-CF3 5-Cl allyl H S
4-C1 5-Cl allyl H S
4-Br 5-Cl allyl H S
4-CF3 5-Cl Me Me S
4-C1 5 Cl . Me Me S
4-Br 5-Cl Me Me S
4-CF3 5-F Me Me S
4-C1 5-F Me Me S
4-Br 5-F Me Me S
~-CF3 5-OCF2H Me Me S
4-C1 5-OCF2H Me Me S
4-8r 5-OCF2H Me Me S
4-CF3 5-OCF3 Me Me S
4-C1 5-OCF3 Me Me S
~0 4-Br 5-OCF3 Me Me S
4-CF3 4-F Me Me S
4-C1 4-F Me Me S
4-Br 4-F Me Me S
4-CF3 5-Br Me Me S
4-C1 5-Br Me Me S
4-8r 5-Fr M0 Me S
4-CF3 5-Cl CH2Ph H S
: 4-C1 5-Cl CH2Ph H S
4-Br 5-Cl CH2Ph H S
4-OCP3 5-Cl C~2Ph H S
4-OCF2H 5-Cl CH2Ph H S
4-CF3 5-F CH2Ph-4-F H S
4-C1 5-F CH2Ph-4-F H S
4-Br 5-F CH2Ph-4-F H S
4-OCF2H 5-F CH2Ph-4-F ~ S
4-OCF3 5-F CH2Ph-4-F H S
4-CF3 5-OCF2H CH2Ph-4-F H S

.

~:

;~0~;74~13 4-Cl 5-OCF2H CH2Ph-4 F H S
4-Br 5-OCF2H CH2Ph-4-F H S
4-OCF3 5-OCF2H CH2Ph-4-F H S
4-OCF2H 5 OCF2H CH2Ph-4-F H S
4-CF3 5-Cl CH2Ph-4-Cl H S
4-Cl 5-Cl CHzPh-4-Cl H S
4-Br 5-Cl CH2Ph-4-Cl H S
4-OCF3 5-Cl CH2Ph-4-Cl H S
4-OCF2H 5-Cl CH~Ph-4-Cl ~ S
4-CF~ H CO2Me H S
lS 4-Cl H CO2Me H S
4-Br H CO2Me H S
4-OCF2H H CO2Me H S
4-F H CO2Me H S
4-CF3 5-Cl C2M~ H S
4-Cl 5-Cl CO2Me H
4-Br 5-Cl CO2Me H S
4-OCF2H 5-Cl CO2Me H S
4-OCF3 S-Cl CO2Me H S
4-NO2 5-Cl CO2Me H S
4-CF3 5-F COzMe H S
4-Cl 5-F CO2Me H S
4-Br 5-F CO2Me H S
4-OCF2H 5-F CO2Me H S
4-OCF3 5-F CO2Me H S
4-CN 5-F CO2Me H S
4-CF3 4-F COzMe H S
4-Cl 4-F CO2Me H S
4-Br 4-F CO2Me H S
4-CF3 4-Cl C2Me H S
q-Cl 4-Cl C2M~ H S
4-Br 4-Cl CO2Me H S
4-CF3 H CO2Me Me S

. .
.~ ~
,:: . -' ~

o -1 R2 ~ ~ A

4-Cl H CO2Me Me S
4-Br H CO2Me Me S
4-OCF2H H CO2Me Me S
4-OCF3 H C2Me Me S
3,4-CF2CF2O H CO2Me Me S
3,4-CH2C(Me~2O H CO~Me Me S
4-CF3 S-Cl CO2Me Me S
4-C1 5-Cl CO2Me Me S
4-Br 5-Cl CO2Me Me S
4-OCF2H 5-Cl CO2Me Me S
4-OCF3 5-Cl CO2Me Me S
3,4-CF2CFzO 5-Cl CO2Me Me S
3r4-cF2c(Me)2o 5-Cl CO2Me Me S
4-CF3 5-F CO2Me Me S
4-C1 5-F CO2Me Me S
4-i3r 5-F CO2Me Me S
4-OCF2H 5-F C2~e Me S
4-OCF3 5-F CO2Me Me S
3,4-CF2CF2O 5-F C2Me Me S
3,4-CH2C(Me)~O 5-F CO2Me Me S
4-CF3 4-F C2Me Me S
4-C1 4-F CO2Me Me S
4-~r 4-F CO2Me Me S
4-OCF3 4-F CO2Me Me S
4-OCF2H 4-F C2M~ Me S
3,4-CF2CF2O 4-F CO2Me Me S
3,4-CH2C(Me)2O 4-F CO2Me Me S
4-CF3 5-OCF2H CO2Me Me S
4-C1 5-OCF2H CO2Me Me S
4-8r 5-OCF2H CO2Me Me S
4-OCF3 5 OCF H CO2Me Me S
4-OCF2H 5-OCF2H CO2Me Me S
3,4-CF2CF2O 5 OCF2H CO2Me Me S

~)57~

R~ 4 A

3,4-CB2C(Me)zO S-OCF2H C02Me Me S
4-OCF2H 6-F C02Me Me S
4-OCF3 6-F C02Me Me S
4-CF3 5-Cl C02Me Et S
4-Cl S-Cl C02Me Et S
4-Br 5-Cl C02Me Et S
4-CF3 5-Cl Co2Me CH2Ph S
4-C1 5-Cl C02~e CH2Ph S
4--~r 5-Cl C02Me CH2Ph S
4-CF3 5-Cl C02Me allyl S
4-C1 5-Cl C02~e allyl S
4-Br 5-Cl C02Me allyl S
4-CF3 5-F C02Et Me S
4-C1 5-F C02Et Me S
4-~r 5-F C02Et Me S
~-CF3 5 F C2CH2CF3 Me S
4-C1 5-F C;2CH2CF3 Me S
4-Br 5-F CO,2CH2CF3 Me S
4-CF3 5-F CO,2Ph Me S
4-C1 5-F COzPh Me S
4-9r 5-F C02Ph Me S
4-CF3 5-Cl C2H ~ S
4-CF3 5-Cl CONHMe H S
4-CF3 5-Cl CONMe H S
4-CF3 5-Cl CONHPh H S
4-CF3 5-Cl CSNMe2 H S
4-CF3 5-Cl propargyl Me S
4-CF3 5-Cl CH2CH2CN Me S
4-CF3 5-Cl CH2C02Me Me S
4-CF3 5-Cl CH20Me Me S

4-CF3 5-Cl OMe H S
~-c~3 5-Cl SMe H S
4-CF3 5-Cl S02Me H S

.' ,:
: ' :

Z6~5i7~0 10~

~1 ~ R3 ~4 4-CF3 5-Cl C(O)Me Me S
4-CF3 S-Cl C(O)Et Me S
4-CF3 5-Cl C(O)Me H S
4-CF3 5-Cl C(O)Et H S
4-CF3 5-Cl CN Me S
4-CF3 5-Cl ~ CN Et S
4-CF3 S-Cl CN CH2Ph S
4-CF3 5-Cl CN H S
4-CF3 4-F allyl H OCH2 4-C1 4 F allyl H OC~2 4-Br 4-F allyl H OCH2 4-OCF2H 4-F allyl H OCH2 4-OCF3 4-F allyl H OCH2 4-CF3 4-Cl allyl H OCH2 4-C1 4-Cl allyl H CCH2 4-Br 4-Cl allyl H OCH2 4-OCF2X 4-Cl allyl H OCH2 4-OCF3 4-Cl allyl H OCH2 4-CF3 S-F propargyl H OCH2 4-C1 5-F propargyl H OCH2 4-Br S-F propargyl H OCH2 4-OCF2H S-F propargyl H OCH2 4-OCF3 5-F propargyl B OCH2 4-CF3 5-Cl Me H OCH2 4-C1 5-Cl Me H OCH2 4-Br 5-Cl Me H OCH2 4-OCF2H 5-Cl Me H OCH2 4-OCF3 5-Cl Me H OCH2 4-CF3 5-CF3 Me H OCH2 4-Cl S-CF3 Me H OCH2 4-Br 5-CF3 Me B OCH2 4-OCF2H 5-CF3 Me H OCH2 .

~S~

Bl ~2 ~ ~

4-OCF3 5 CF3 Me H OCH2 4-C~3 5-OCF2H Me ~ OCH2 4-Cl 5-OCF2H Me H OCH2 4-Br 5-OCF2H Me H OCH2 4-OCFzH 5-OCF2H Me H OCH2 4-OCF3 5-OCF2H~ M~ H OCH2 4-CF3 4-F CH2Ph H OCH2 4-C1 4-F CH2Ph H OCH2 4-~3r 4-F CH2P~ H OCH2 4-OCF2H 4-F CH2Ph H OCH2 4-OCF3 4-F CH2Ph H OCH2 4-CF3 4-Cl CH2Ph H OCH2 4-Cl 4-Cl CH2Ph H OCH2 4-Br 4-Cl CH2Ph H OCH2 4-OCF2H 4-Cl CH2Ph H OCH2 ~0 4-OCF3 4-Cl CH2Ph H OCH2 4-CF3 5-F CR2Ph H OCH2 4-Cl 5-F CH2Ph H OCH2 4-Br 5-F CHzPh H OCH2 4-OCF2H 5-F CH2Ph H OCH2 4-OCF3 S-F CH2Ph H OCH2 4-CF3 5-Cl CB2Ph-4-Cl H OCH2 4-Cl 5-Cl CH~Ph-4-Cl H OCH2 4-Br 5-Cl CH2Ph-4-Cl H OCH2 4-OCF2H 5-Cl CH2Ph-4-Cl H OCH2 4-OCF3 5-Cl CH2Ph-4-Cl H OCH2 4-CF3 5-CF3 CH2Ph-4-Cl H OCH2 4-Cl S-CF3 CH2Ph-4-Cl B OCH2 4-Br 5-CF3 CH2Ph-4-Cl !3 OCH2 4-OCF2H 5-CF3 CH2Ph-4-Cl H OCH2 4-OCF3 5-CF3 CH2Ph-4-Cl H OCH2 g-CF3 5-OCF2H CH2Ph-4-Cl H OCH2 .': ' ~ ~ . .

ji7~

Rl ~ ~ R4 A

4-C1 5-OCF2H C~2Ph-4-Cl H OC~2 4-Br 5-OCF2H CH2Ph-4-Cl H OCH2 4-OCF2H 5-OCF2H CH2Ph-4-Cl }I OCH2 4-OCF3 5-OCFzH CH2Ph-4-Cl H OCH2 4-CF3 4-F CO2Me H OCH2 4-C1 4-F CO2Me H OCH2 4-Br 4-F CO2Me H OCH2 4-OCF2H 4-F C2M~ H OCH2 4-OCF3 4-F CO2Me H OCH2 4-CF3 4-Cl CO2Me H OCH2 4-C1 4-Cl CO2Me H OCH2 4-Br 4-Cl CO2Me H OCH2 4-OCF2H 4-Cl C02Me H OCH2 q-OCF3 4-Cl CO2Me H OCH2 4-CF3 5-F CO2Me H OCH2 4-C1 5-F CO2Me H OC~2 4-Br 5-F CO2Me H OCH2 4-OCF2H 5-F C~2Me H OCH2 4-OCF3 5-F CO2Me H OCH2 4-CF3 5-Cl CO2Me H OCH2 4-C1 5-Cl CO2Me H OCH2 4-Br 5-Cl C2Me H OCH2 : 4-OCF2H 5-Cl CO2Me H OCH2 4-OCF3 5-Cl CO2Me H OCH2 4-CF3 5-CF3 CO2Me H OCH2 4-Cl 5-CF3 CO2Me H OCH2 4-8r 5-CF3 CO2Me H OCH2 4-OCF2~ 5-CF3 CO2Me H OCH2 4-OCF3 5-CF3 CO2Me H OCH2 4-CF3 5-OCF2H CO2Me H OCH2 4-C1 5-OCF2H CO2Me H OCH2 4-Br 5-OCF2H CO2Me H OCH2 ,, ~. ,.j-. :.
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4-OCF2H 5-OCF2H CO2Me ~ OCH2 4-OCF3 5-OCF2H CO2Me H OCH2 4-CF3 4-F CO2Me Me OCH2 4-C1 4-F CO2Me Me OCH2 4-Br 4-F CO2Me Me OC~2 4-OCF2H 4-F . COzMe Me OCH2 4-OCF3 4-F CO2Me Me OC}~2 4-CF3 4-Cl CO2Me Me OC82 4-C1 4-Cl CO2Me Me OCH2 4-Br 4-Cl C2Me Me OCH2 4-OCF2H 4-Cl CO2Me Me OC~2 4-OCF3 4-Cl CO2Me Me OCH2 4-CF3 5-F CO2Me Me OC~12 4-C1 5-F CO2Me Me OCH~
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21[3~)5~

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Rl R2 ~3 4-C1 5-F 4-F Ph H CH2CH2 4-Br 5-F 4-F-Ph H CH2CH2 4-OCF2H 5-F 4-F-Ph H CH2CH2 4 CF3 5 P 4-Cl-Ph H CH2C~2 4-C1 5-F 4-Cl-Ph H CH2tH2 4-Br 5-F 4-Cl-Ph H CH2CH2 4-OCF2H 5-F 4-Cl-Ph H CH2CH2 4-CF3 5-F 4-OMe H CH2C112 4-C1 5-F 4-C~e H CH2CH2 4-Br 5-F 4-OMe H CH2CH2 4-OCF2H S-F 4-OMe H CH2CH2 4-CF3 5-Cl Ph Me CH2C~2 ~-Cl 5-Cl Ph Me CH2CH2 4-Br 5-Cl Ph Me CH2CH2 4-OCF2H 5-Cl Ph Me CH2CH2 4-C~3 5-C1 4-Cl-Ph Me CH2CHz 4-C1 5-C1 4-Cl-Ph Me CH2CH2 4-Br 5-C1 4-Cl-Ph Me CH2CH2 4-OCF2H 5-C1 4-Cl-Ph Me CH2CH2 4-CF3 5-F Ph Me CH7C~2 4-C1 5-F Ph Me CH2CH2 4-Br 5-F Ph Me CH~CH2 4-OCF2H 5-F Ph Me CH2C~2 4-CF3 5-F 4-Cl-Ph Me CH2CH2 4-C1 5-F 4-Cl-Ph Me CH2C~2 4-Br 5-F 4-Cl-Ph Me CH2CH2 4-OCF2H 5-F 4-Cl-Ph Me C~2CH2 4-CF3 5-Cl CO2Me H C~2CH2 4-C1 5-Cl CO2Me H C~2CH2 4-8r 5-Cl COzMe H CH2CH2 4-OCF2H 5-Cl C2Me H CH2C~2 4-CF3 5-Cl CO2Me Me CH2CH2 4-C1 5-Cl Ct)2Me Me CH2CH2 .

Z0~7~

Rl ~ B3 ~ A

4-Br 5-Cl C02Me Me CH2CH2 4-OCF2H 5-Cl CO2Me Me CH2C~2 4-CF3 4-F CO2Me H CH2C~2 4-C1 4-F C02Me H CH2CH2 4-~3r 4-F C2M~ H CH2CH2 4-OCF2H 4-F CO2Me H CH2CH2 4-CF3 4-F CO2Me Me C~2CH2 4-C1 4-F C02Me Me CHzCH2 4-Br 4-F CO2Me Me CH2C~2 4-OCF2H 4-F CO2Me Me C~2CH2 4-OCP3 5-C1 4-Cl-Ph H CH2CH2 4-OCF2CF2H 5-C1 4-Cl-Ph H CH2CH2 3-Cl,4-CF3 5-C1 4-Cl-Ph H CH2CH2 3,4-CH2CtMe)20 5-C1 4-Cl-Ph H CH2CH2 3,4-CF2CF20 5-C1 4-Cl-Ph H ~H2CH2 4-C~ 5-Cl 4-Cl-Ph H CH2CH2 4-N2 5-C1 4-Cl-Ph H CH2CH2 4-F 5-Cl 4-Cl-Ph H CH2CH2 3,4-di-C1 5-Cl 4-Cl-Ph H C~2CH2 4-CO2Me 5-Cl ~-Cl-Ph H CH2C~I2 4-SCF2H 5-Cl 4-Cl-Ph H CH2CH2 4-SCF2CF2H 5-Cl 4-Cl-Ph H CH2CH2 4-OCH2CF3 5-C1 4-Cl-Ph H CH2CH2 4-OCF3 5-Cl Ph H CH2CH2 4-OCF2CF2H 5-Cl Ph H CH2CH2 3~ 3-Cl,4-CF3 5-Cl Ph H C82CH2 3,4-CH2C~Me)20 5-Cl Ph H CH2CH2 3,4-CF2CF20 5-Cl Ph H C~2CH2 4-CN 5-Cl Ph H CH2C~2 4-NO2 5-Cl Ph H CH2CH2 4-F 5-Cl Ph H CH2C~I2 3,4-di-C1 5-Cl Ph H CH2CH2 4-CO2Me 5-Cl Ph ~ CH2CH2 -r t~

Rl R2 ~ R4 4-SCF2H 5-Cl Ph H C~2CIt2 4-SCF2CF2H 5-Cl Ph H CH2CH2 4-OCH2CF3 5-Cl Ph H CH2CH2 2~7~

Q-NHCNH ~ R

O Bl 2 ~3 ~4 Q-2 OCF3 H H H Cl~z Q-2 CF3 H Me H CH2 Q-2 OCF3 H Me H CH2 . 20 0-2 CF3 H 9 F-Ph H CH2 O-2 OCF3 H 4-F-Ph H CH2 Q-2 CF3 H 4-Cl-Ph H CH2 ~ Q-2 OCF3 H 4-Cl-Ph 8 CH2 : Q-2 CF3 S-CF3 Me H CH2 ~ 25 Q-2 OCF3 5-CF3 Me H CH2 : Q-2 CF3 S-CF3 4-F-Ph H CH2 Q-2 OCF3 5-CF3 4-F-Ph H CH2 : ~ Q-2 CF3 5-CF3 4-Cl-Ph H CH2 Q-2 OCF3 5-CF3 4-Cl-Ph H CH2 U-2 CF3 5-Cl Me H CH2 n- 2 OCF3 5-Cl Me H CH2 Q-2 CF3 5-C1 4-F-Ph H CH2 Q-2 OCF3 5-C1 4-F-Ph H CH2 Q-2 CF3 H Me H O

',~, , '. ' , ,. :: . ~ ::
, ~ !3057~

~1 -R-2 ~ ~ A

g_2 OCF3 H Me H O
Q-2 CF3 H 4-F-Ph Me O
9-2 OCF3 H 4-F-Ph ~le O
Q-Z CF3 H 4-Cl-Ph Me O
Q-20CF3 H 4-Cl-Ph .Me O
Q-2 CE'3 H i-Pr H O
Q-2 OCF3 H i-Pr H O

Q-2 CF3 5-CF3 Me H O
Q-2 ocF3 5-cF3 Me H O
Q-2 CF3 5-CF3 i Pr H O
Q-20CF35-CF3 i-Pr H O
Q-2 CF3 5-CF3 4-F-Ph Me O
Q-20CF3 5-CF3 4-F-Ph Me O

Q-3 CF3 H Me H CH2 Q-3 OCF3 H Me H CH2 Q-3 CF3 H 4-F-Ph H CH2 Q-3 OCF3 H 4-F-Ph H CH2 0-3 CF3 H 4-Cl-Ph H C~2 Q-3 OCF3 H 4-Cl-Ph H CH2 Q-3 CF3 4-CF3 Me H CH2 Q-3 OCF3 4-CF3 Me H CH2 Q-3 CF3 4-CF34-F-Ph H CH2 0-30CF3 4-CF3 4-F-Ph H CH2 Q-3 CF3 4-CF3 4-Cl-Ph H CH2 0-30CF3 4-CF3 4-Cl-ph H C~2 0-3 CF3 4-CF3 Me H CH2 Q-30CF3 4-CF3 Me H CH2 Q-3 CF3 4-CF34-F-Ph H CH2 57~() Rl R2 ~ R4 Q-3 OCF3 4-CF3 4-F-Ph H CH2 Q-3 CF3 H Me H O
Q-3 OCF3 H Me H O
Q-3 CF3 H 4-F-Ph Me O
O-3 OCF3 H 4-F-Ph Me O
Q-3 CF3 H 4-Cl-Ph Me O
0-3 OCF3 H 4-Cl-Ph Me O
Q-3 CF3 H i-Pr H 0 Q-3 OCF3 H i-Pr H O

Q-3 CF3 4-CF3 Me H O
Q-3 GCP3 4-CF3 Me H O
Q-3 CF3 4-CF3 i-Pr H O
Q-3 OCF3 4-CF3 i-Pr H O
Q-3 CF3 4-CF3 4-F-Ph Me O
Q-3 OCF3 4-CF3 4-F-Ph Me O

Q-4 CF3 H Me H CH2 Q-4 OCF3 H Me H CX2 Q-4 CF3 H 4-F-Ph H CH2 Q-4 OCF3 H 4-F-Ph H CH2 Q-4 CF3 H 4-Cl-Ph H CH2 Q-4 OCF3 H 4-Cl-Ph H C~2 Q~4 CF3 5-CF3 Me H CH2 Q-4 OCF3 5-CF3 Me H CH2 Q-4 CF3 5-CF3 4-F-Ph H CH2 Q-4 OCF3 5-CF3 4-F-Ph H CH2 Q-9 CF3 5-CF3 4-Cl-Ph H CH2 Q-4 OCF3 5-CF3 4-Cl-Ph H Cl~2 Q Rl -2 ~. E~4 A

0-4 CF3 4-F Me H CH2 Q-4 OCF3 4-F Me H CH2 Q-4 CF3 4-F 4-F-Ph H CH2 Q-4 OCF3 4-F 4-E'-Ph E~ CH2 Q-4 CE?3 H H H O
Q-4 OCF3 H H E~ O
Q-4 CF3 H Me H O
0-4 OCF3 H Me H O
Q-4 CF3 H 4-F-Ph Me O
Q-4 OCF3 E~ 4-F-Ph Me O
Q-4 CF3 H 4-Cl-Ph Me O
Q-4 OCF3 H 4-Cl-Ph Me O
Q-4 CF3 H i-Pr E~ O
Q-4 OCF3 H i-Pr H O

Q-4 CF3 5-CF3 Me H O
Q-40CF3 5-CF3 Me H O
Q-4 CF3 5-CF3 i-Pr H O
0-4 OCF3 5-CF3 i-Pr H O
Q-4 CF3 5-CF3 4-F-Ph Me O
Q-4 OCF3 5-CF3 4_F_Ph Me O

Q-5 CF3 H Me H CH2 Q-5 OCF3 El Me E~ CH2 Q-5 CF3 H 4-F-Ph H CH2 Q-5 OCF3 H 4-F-Ph H CH2 Q-5 CF3 H 4-Cl-Ph H CH~
Q-5 OCF3 H 4-Cl-Ph H CH2 Q-5 CF3 5-CF3 ~'lf~ H CH2 2-5 OCF3 5-CF3 Me H CH2 Q-5 CF3 5-CF3 4-F-Ph E~ CH2 ' '., : :

- ~
.~

7~

Q Rl --2 ~ ~ A

Q-5 OCF3 5-CF3 4-F-Ph H CH2 0-5 CF3 5-CF3 4-Cl-Ph H C~12 0-5 OCF3 5-CF3 4-Cl-Ph H CH2 O-5 CF3 4-F Me H CH2 Q-5 OCF3 4-F Me ~ CH2 Q-5 CF3 4-F 4-F-Ph H CH2 Q-5 Ot:F34-F 4-F-Ph H CH2 ~-5 OCF3 5-CF3 H H O
Q-5 CF3 S-CF3 Me H O
Q-5 OCF3 5-CF3 Me H O
Q-5 .F3 5-CF3 4-F-E'h Me O
Q-5 OCF3 5-CF3 4-3F-Ph Me O
Q-5 CF3 5-CF3 4-Cl-Ph Me O
Q-5 OCF35-CF34-Cl-Ph Me O
Q-5 CF3 5-CF3 i-Pr H O
0-5 OCF3 5-CF3 i-Pr H O
Q-5 CF3 5-Cl H H O
Q-5 OCF3 5-Cl H H O
0-5 CF3 5-Cl Me H O
Q-5 OCF3 5-Cl Me H O
Q-5 CF3 5-Cl i-Pr H O
Q-5 OCF35-Cl i-Pr H O
Q-5 CF3 5-C1 4-F-Ph Me O
Q-5 OCF35-C1 4-F-Ph Me O

- ., ~ -. :
: ~. : .:;

7~

13~

o Q-NHCNH ~ R

(V = S) _ ~ R2 R3 ~

g-6 OCF3 H H H CH2 Q-6 CF3 H Me H t:H2 Q-6 OCF3 H Me H t:H2 Q-6 CF3 H 4-F-Ph H CH2 0-6 O;F3 H 4-F-Ph H ~'H2 Q-6 CF3 H 4-Cl-Ph H ~H2 0-6 OCF3 H 4-Cl-Ph H ~H2 : Z5 0-6 CF3 5-Cl Me H CH2 Q-6 OCF3 5-Cl Me H CH2 Q-6 CF3 5-C1 4-F-Ph H CH2 Q-6 OCF3 5-C1 4-F-Ph H CH2 Q-6 CF3 5-C1 4-Cl-Ph H CH2 Q-6 OCF3 S-Cl 4-Cl -Ph H CH2 g-6 CF3 5-F Me H CH2 Q-6 OCF3 5-F Me H CH2 Q-6 CF3 5-F 4-F-Ph H CH2 Q-6 OCF3 5-F 4-F-Ph H CH2 ~0~

Q Rl ~. 2 ~ R4 Q-6 CF3 H Me H O
Q-6 OCF3 H Me H O
Q-6 CF3 H 4-F Ph Me O
Q-6 OCF3 H 4-3F-Ph Me O
Q-6 CF3 H 4-Cl-Ph Me O
Q-6 OCF3 H 4-Cl-Ph Me O
Q-6 CF3 H i-Pr H O
Q-fi OCF3 H i-Pr H O
Q-6 CF3 5-Cl H H O
Q-6 OCF3 5-Cl H H O
Q-5 CF~ 5-Cl Me H O
Q-6 OCF3 5-Cl Me H O
Q-6 CF3 5-Cl i-Pr H O
Q-6 OCF3 5-Cl i-Pr H O
Q-6 CF3 5-C1 4-F-Ph Me O
Q-6 OCF3 5-C1 4-F-Ph Me O

Q-7 OCF3 H Fl H CH2 Q-7 CF3 H Me H CH2 Q-7 OCF3 H Me H CH2 Q-7 CF3 H g-F-Ph H CH2 Q-7 OCF3 H 4-F-Ph H CH2 Q-7 CF3 H 4-Cl-Ph H CH2 Q-7 OCF3 H 4-Cl-Ph H CH2 C?-7 CF3 4-Cl Me H CH2 3 0 Q-7 OCF3 4-Cl Me H CB2 Q-7 CF3 4-C1 4-F-Ph H CH2 Q-7 OCF3 4-C1 4-F-Ph H CH2 Q-7 CF3 4-C1 4-Cl-Ph H CH2 Q-7 OCF3 4-C1 4-Cl-Ph H CH2 3 S Q-7 CF3 4-F Me H CH2 0 7 OCF3 4-F Me H CH2 Q-7 CF3 ~-F 4-F-Ph H CH2 ~O~ O

Q Rl R2 ~ R~ A

Q-7 OCF3 4-F 4-F-Ph H CHz Q-7 CF3 H Me H O
Q-7 OCF3 11 Me H O
0-7 CF3 H 4-F-Ph Me O
Q-7 OCF3 H 4-3F-Ph Me O
Q-7 CF3 H 9-Cl-Ph Me O
Q-7 OCF3 H 4-Cl-Ph Me O
Q-7 CF3 H i-Pr H O
Q-7 OCF3 H i-Pr H O

Q-7 CF3 4-F Me H O
Q-7 OCF3 4-F Me H o Q-7 CF3 4-F i-Pr H C) 0-7 OCF3 4-F i-Pr H
Q-7 CF3 4-F 4-F-Ph Me O
Q-7 OCF3 ~-F 4-F-Ph Me O

0-8 CF3 H Me H CH2 Q-8 OCF3 H Me H CH2 Q-8 CF3 H 4-F-Ph H CH2 Q-8 OCF3 H 4-F-Ph H CH2 O-8 CF3 H 4-Cl-Ph H CH2 Q-8 OCF3 H 4-Cl-Ph H C~12 Q-8 CF3 4 F Me H CH2 Q-8 OCF3 4-F Me H CH2 Q-8 CF3 4-F 4-F-Ph H CH2 O-8 OCF3 4-F 4-F-Ph H CH2 Q-8 CF3 4-F 4-Cl-Ph H CH2 Q-8 OCF3 4-F 4-Cl-Ph H CH2 7~0 Q ~ ~ ~ ~ A

Q-8 CF3 5-Cl Me H CH2 Q-3 OCF3 5-Cl Me H CH2 Q-8 CF3 S-Cl 4-F-Ph H CH2 Q-8 OCF3 5-C1 4-F-Ph H CH2 Q-8 CF3 4-F Me H O
Q-8 OCF3 4-F Me H O
Q-8 CF3 4-F 4-F-Ph Me O
Q-8 OCF3 4-F 4-3F-Ph Me O
Q~8 CF3 4-F 4-Cl-Ph Me O
Q-8 OCF3 4-F 4-Cl-Ph Me O
Q-8 CF3 4-F i-Pr H O
Q-8 GCF3 4-F .i-Pr H O
Q-8 CF3 5-Cl H H O
Q-8 OCF3 5-Cl H H C) Q-8 CF3 5-Cl Me H O
Q-8 OCF3 5-Cl Me H O
Q-8 CF3 5-Cl i-Pr H
Q-8 OCF3 S-Cl i-Pr H O
Q-8 CF3 5-C1 4-F-Ph Me O
Q-8 OCF3 5-C1 4-F-Ph Me O

. ` :`
': ' '~ .. ' X~3.~

Art_ropodicidal FQr ulation-and ~se The compounds of this invention will generally be used in formulation with a carrier comprising a liquid or solid diluent or an organic solvent.
Useful formulations of the compounds of ~ormula I can be prepared in conventional ways. They include dusts, granules, pellets, solutions, suspensions, emulsions, baits, wettable powders, emulsifiable concentrates, dry flowables and the like. Many of these can be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from about one to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 1% to 99% by weight of active ingredient~s) and at least one of a) about 0.1% to 20% surfactant(s) and b) about 5% to 99% solid or liquid diluent(s). More specifically, they will contain these ingredients in the following approximate proportions:
Percent by Weight Active In3Iedient Diluentts~ Surfactant~s~
Wettable Powders25-90 0-79 1-10 Oil ~uspensions, 1-50 40-95 0-35 Emulsions, Solutions, ~including Emulsifiable Concentrates) Dusts 1-25 70-99 0-5 Granules, Baits0.01-95 5-99 0-15 arld Pellets High Strength 90-99 0-10 0-2 ~ompositions Z~157~0 Lower or higher ]evels of active ingredient can, of course, be present depending on the intended use and the physical properties of the compound. Higher ratios of surfactant to active ingredient are some-times desirable, and are achieved by incorporation into the formulation or by tank mi~ing.
Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Dorland Books, Caldwell, New Jersey. The more absorptive diluents are preferred for wettable powders and the denser ones for dust~.
Typical liquid diluents and solvents are described in Marsden, "Solvents Guide," 2nd Ed., Interscience, New York, 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0C.
Mc~u~cheon's Detergents and Emulsifiers Annual", Allured Publ. Corp.~ Ridgewood, New Jersey, as well as Sisely and Wood, "Encyclopedia of Surface Active Agents", Chemical Publ. Co., Inc., New York, 1964, list surfactants and reco~nended uses. All formula-tions can contain minor amounts of additives to reducefoam, caking, corrosion, microbiological growth, etc.
Preferably, ingredients should be approved by the U.S.
EnYironmental Protection Agency for the use intended.
T~e methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer or fluid energy mill. Suspensions are prepared by wet milling (see, for example, U.S. 3,060,084). Granules and pellets can be made by spraying the active material upon preformed granular carriers or by 5~

agylomeration techniques. See Browning, ~Agglomeration", Chemical En~in~erinq, December 4, 1967, pages 147 and following, and "Perry's Chemical Engineer's Handbook~', 4th Ed., McGraw-Hill, New York, 1963, pa~es 8 to 59 and following.

~xample A
~mulsifiable Concentrate 2-(S-chloro-2,3-dihydro-2-phenyl-lH-inden-l-ylidene)-N-[4-(trifluoromethyl)phenyl]hydrazinecarbox-amide 20%
blend of oil soluble sulfonates and polyo~yethylene ethers 10%
isophorone 70%
The ingredients are combined and stirred with gentle warming to speed solution. A fine screen filter is included in packaging operation to insure the absence of any extraneous undissolved material inthe product.

E~m~
Wettable Powder 2-~S-chloro-2,3-dihydro-2-phenyl-lH-inden-l-ylidene)-N-[4-(trifluoromethyl)phenyl]hydrazinecarbo~-amide 30%
sodium alkylnaphthalenesulfonate 2%
sodium ligninsulfonate 2%
synthetic amorphous silica 3%
kaolinite 63%
The active ingredient is mi~ed with the inert materials in a blender. After grinding in 3 hammer-mill, the material is re-blended and sifted through a 50 mesh screen.

! . . .

, .

E~ampl~ C
Dus~
Wettable powder of Example B 10%
pyrophyllite tpowder) 90%
The wettable powder and the pyrophyllite diluent are thoroughly blended and thPn packaged. The product is suitable for use as a dust.

E~ample D
Gr~a~l~
2-[5-chloro-2-~4-chlorophenyl)-2,3-dihydro-lH-inden-l-y lidene~-N-[4-(trifluoromethyl)pllenyl]hydrazine-carboxamide 10%
attapulgite granules ~low volative matter, 0.71/0.30 mm; U.S.S. No.
Z5-50 sieves~ 90 The active ingredient is dissolved in a volatile solvent such as acetone and sprayed upon dedusted and pre-warmed attapulgite granules in a double cone blender. The acetone is then driven off by heating.
The gran-lles are then allowed to cool and are packag~d.
Example Granule Wettable powder of E~ample B 15%
gypsum 69%
potassium sulfate 16%
The ingredients are blended in a rotating mixer an~ water sprayed on to accomplish granulation. When most of the material has reached the desired range of 0.1 to 0.~2 mm (U.S.S. No. 18 to 40 sieves), the gran-ules are removed, dried, and screened. Oversize ~'; ' , ~ .

';

2 0 ~97 ~ O

material is crushed to produce additional material in the desired range. These granules contain 4.5% active ingredient.

Example F
Solution 2-(5-chloro-2,3-dihydro-2-phenyl-lH-inden-l-ylidene~-N-[4-(trifluoromethyl)phenyl]hydrazinecarbox-amide 25%
N-methyl-pyrrolidone 75%
The ingredients are combilled and stirred to produce a solution suitable for direct, low volume applicatîon.

~xam~le G
~ueo~s Sus~ension 2-(5-chloro-2,3-dihydro-2-phenyl-lH-inden-l-ylidene)-N-[4-(trifluoromethyl)phenyl]hydrazinecarbox-amide 40~
polyacrylic acid thickener 0.3%
dodecyclophenol polyethylene glycol ether 0 5%
disodium phosphate 1.0%
monosodium phosphate 0.5~
- polyvinyl alcohol 1.0%
water 56.7%
The ingredients are blended and ground together in a sand mill to produce particles essentially all under 5 microns in size.

, .
;

Example 11 Oil Suspension 2-[5-chloro-2-(9-chlorophenyl~-2,3-dihydro-lH-inden-l-y lidene]-N-~4-~trifluoromethyl)phenyl3hydrazine-carbo~amide 35.0%
blend of polyalcohol carboxylic 6.0%
esters and oil soluble petroleum sulfonates ~ylene range solvent 59.0%
The ingredients are combined and ground together in a sand mill to produce particles essentially all below 5 microns. The product can be used directly, extended with oils, or emulsified in water.

Example I
~n~1es 2-(5-chloro-2,3-~ihydro-2-phenyl-lH-inden-l-ylidene)-N-[4-(trifluoromethyl)phenyl]hydrazinecarbo~-amide 3,0%
blend of polyethoxylated nonyl 9.0 phenols and sodium dotlecyl-benzene sulfonates ~5 ground up corn cobs 88.0%
The active ingredient and surfactant blend are dissolved in a suitable solvent such as acetone and sprayed onto the ground corn cobs. The granules are then dried and packaged. Compounds of Formula I can also be mixed with one or more other insecticides, fungici~es, nematocides, bactericides, acaricides, or other biologically active compounds to form a multi-componerlt pesticide giving an even broader spectrllm of effective agricultural protection.
Examples of other agricultural protectants with ~l~ich compounds of the present invention can be mixed or formulated are:

' -. . . .

~0~3~ j7~

Insecticides:
5 3-hydroxy-N-methylcrotonamide(dimethylphosphate)ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran) 0-[2,4,5-trichloro--(chloromethyl)benzyl]phosphoric acid, O',O'-dimethyl ester (tetrachlorvinphos) 2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion) phos~horothioic acid, O,O-dimethyl, O-p-nitrophenyl ester (methyl parath-on) methylcarbamic acid, ester with ~-naphthol ~carbaryl) methyl O-(methylcarbamoyl)thiolacetohydroxamate (methomyl) N'-(4-chloro-Q-tolyl~-N,N-dimethylformamidine (chlordimeform) O,O-~iethyl-0-(2-isopropyl-4-methyl-6-pyri1nidylphos-phorothioate (diazinon) octachlorocamphene ttoxaphene) O-e~hyl O-p-nitrophenyl phenylphosphonothioate (EPN) (S)-a-cyano-m-phenoxybenzyl(lR,3R)-3-(2,2-dibromovinyl) -2,2-dimethylcyclopropanecarboxylate (deltamethrin) Methyl-N',N'-dimethyl-N-[(methylcarbamoyl)oxy]-l-~hioox amimidate (oxamyl) cyano(3-phenoxyphenyl)-methyl-4-chloro-a-ll-methyl-ethyl)ben~eneacetate (fenvalerate) (3-phenoxyphenyl)methyl(+)-cis,~3n~-3-(Z,2-dichloro ethenyl)-2,2-dimethylcyclopropanecarboxylate (perme-thrin) a-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (cypermethri~) .:, - . ~

'7~

O-ethyl-S-(P-chlorophenyl)ethylphosphonodithioate ~profenofos) phosphorothiolothionic acid, O-ethyl-0-[4-(methylthio)-phenyl]-S- -propyl ester (sulprofos).

Additional insecticides are listed hereafter by their common names: t~iflumuron, diflubenzuron, methoprene, buprofezin, thiodicarb, acephate, azinphos-methyl, chlorpyr.ifos, dimethoate, fonophos, isofenphos, methidathion, methamidiphos, ~onocrotphos, phosmet, phospllamidon, phosalone, pirimicarb, phorate, profenofos, terbufos, trichlorfon, methoxychlor, bifenthrin, biphenate, cyfluthrin, fenpropathrin, fluvalinate, flucythrinate, tralomethrin, metal-dehyde and rotenone.

Fun i~es:
methyl 2-benzimidazolecarbamate (carbendazim) tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (mane~) 1,4-dichloro-2,5-dimethoxybenzene (chloroneb) methyl l-(~utylcarbamoly)-2-b~nzimidazolecarbamate (benomyl) : 1-[2-(2,4-dichlorophenyl~-4-propyl-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole (propiconazole~
2-cyano-N-ethylcarbamoy-2-methoxyiminoacetarnide (cyrnoxanil~
1-(4-chlorophenoxy)-3,3-dimethyl-1-(lH-1,2,4-triazol-1-yl)-2-butanone ~triadimefon) N-(trichloromethylthio)tetrahydrophthalimide (captan) N-~trichloromethylthio)phthalimide (folpet) l-[[[bis(4-fluorophenyl)]~methyl]silyl]methyl]-lH-1,2,4-triazole.

7~

Ne~Q~id~:
S-methyl l-(dimethylcarbamoyl)-N-tmethylcarbamoyloxy)-thioformimidate S-methyl l-carbamoyl-N-(methylcarbamoyloxy)thioformimidate N-isopropylphosphoramidic acid, 0-ethyl 0~-[4-(~ethylthio)-m-tolyl]diester (fenamiphos) Bactericides:
tribasic copper sulfate streptomycin sulfate 1~
Acaricides:
senecioic acid, ester with 2-sec-butyl-4,6-dinitro-phenol (binapacryl) 6-methyl-1,3-cithiolo~4,5-~]quinoxalin-2-one (oxythioquinox) ethyl 4,4'-dichloro~enzilate (chlorobenzilate) 1,1-bis(~-chlorophenyl)-2,2,2-trichloroethanol (dicofol) bis(pentachloro-2,~-cyclopentadien l-yl) (dienochlor) tricyclohexyltin hydro~ide (cyhexatin) trans-5-(4-chlorophenyl)-N-cyclohe~yl-~-methyl-2-oxo-: thiazolidine-3-carboxamide ~hexythiazox) amitraz propargite fenbutatin-oxide BioloaiC~l ~acillus thllringiensis Avermectin B.

',.
, ;

Z~5i7~1 1~5 Uti_i~X
Th~ compounds of this invention exhibit activity against a wide spectrum of foliar and soil inhabiting arthropods which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will recognize that not all compounds are equally effective against all pests but the compounds of this invention display activity against economicallv important agronomic, forestry, greenhouse, ornamental food and fiber product, stored product, and nursery pests, such as:

larvae of the order Lepidoptera including fall and beet armyworm and other ~pQd~
spp., tobacco budworm, corn earworm and other ~li~hi~ spp., European corn borer, navel orangeworm, stalk/stem borers and other pyralids, cabbage and soybean loopers and otller loopers, codling moth, grape berry moth and other tortricids, black cutworm, spotted cutworm, other cutworms and other noctuids, diamondback moth, green cloverwor~, velvetbean caterpillar, green cloverworm, pink bollworm, gypsy moth, and spruce budworm;

foliar feeding larvae and adults sf the order Col~optera including Colorado potato beetle, Mexican bean beetle, flea beetle, Japanese bQetles, and other leaf beetles, boll weevil, .

~5~7'~C9 rice water weevil, granary weevil, rice weevil and oLher weevil pests, and soil inhabiting insects such as Western corn rootworm and other Diabr~t~ spp., Japanese beetle, European chafer and other coleopteran grubs, and wirewurms;

adults and larvae of the orders Hemiptera and _omoptera including tarnished plant bug and other plant bugs ~milidae), aster leafhopper and o~her leafhoppers ~cicadellidae), rice planthopper, brown planthopper, and other planthoppers ~lgoro~a.), psylids, whiteflies ~aleurodidae), aphids (aphi~
scales (coccidae and diaspididae), lace bugs ~tin.aidae), stink bugs ~Dentatomidae), cinch bugs and other seed bugs ~lygaeida.~), cicadas (cicadidae), spittlebugs ~cerc.o~ ), squash bugs (cQreidae), red ~ugs and cotton stainers ~y~Q~ori.da~);

adults and larvae of the order ~cari (mites) including European red mite, two spott~d spider mite, rust mites, McDaniel mite, and foliar feeding mites;

adults and immatures of the order Ortho t~ra including grasshoppers;

adults and immatures of the order L~Ptera including leafminers, midges, fruit flies (~phritida~), and soil maggots; S

2~

adults and il~unatures of the or~er ~hYsanoPtera including onion thrips and other foliar feeding thrips.

The compounds are also active against economically important livestock, household, public and animal health pests such as:

insect pests of the order HYmenopt~ra including carpenter ants, bees, hornets, and wasps;
insect pests of the order _iptera including house files, stable flies, face flies, horn 1ies, blow flies, and other muscoid fly pests, horse flies, deer flies and other Brachycera, mosquitoes, black flies, biting midges, sand flies, sciarids, and other Ne~ Q~çra;

insect pests o~ the order Orthoptera including cockroaches and crickets;

insect pests of the order I~P.tera including the Eastern subterranean termite and other termites;
insect pests of the order Malloph~aa and noplura including the head louse, body louse, chicken head louse and other sucking and chewing parasitic lice that attack man and animals;

'~ '" ' insect pests of the order Siphonoptera including the cat flea, dog flea and other fleas.

The specific species for which control is e~emplified are: fall armyworm, Spo~optera fruigiperd~; tobacco budworm, ~eliothis _~L~çn~;
boll weevil, ~nthonomus qrandis; aster leafhopper, rosteles fascifrons; southern corn rootworm, Diabrotica unde~im~unctata. The pest control protection afforded by these compounds of the present invention is not limited, however to these species.
Ap~:L~n Arthropod pests are controlled and protPction of agronomic crops, animal and human health is achieved by appl~ing one or more of the Formula I ~ompounds of this invention, in an effective amount, to the locus of infestation, to the area to be protect~d, or directly on the pests to be controlled. Because of the diversity of habitat and behavior of these arthropod pest species, many different methods of application are employed. A preferred method of application is by spraying with equipment that distributes the compound in the environment of the pests, on the foliage, animal, person, or premise, in the soil or animal, to the plant part that is infested 3~ or needs to be protected. Alternatively, granular for~ulations of these to~icant compounds can be applied to or incorporated into the soil.
Other methods of application can also be employed including direct and residual sprays, aerial, baits, earLags, boluses, foggers, aerosols, and many oLIIers. The compounds can be incorporated into baits .~

20~574~0 19~
that are consumed by the arthropods or in devices such as traps and the like which entice them to ingest or otherwise contact the compounds.
The compounds of this invention can be applied in their pure state, but most often application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, and synergists such as piperonyl butoxide often enhance the efficacy of the compounds of Formula I.
The rate of application of the Formula I
compounds required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, etc. In general, application rates of .05 to ~ kg of active ingredient per hectare are sufficient to provide large-scale effective control of pests in agronomic ecosystems under normal circumstances, but as little as .001 kg/hectare or as much as a kg hectare may be required. For nonagronomic applicati~ns, effective use rates will range from about 0.1 to 5 mg/square foot but as little as about 0.01 mg/square foot or as much as lS
mg/square foot may be required~
The following Examples demonstrate the control efficacy of compounds of Formula I on specific pests;
see Tables 1 to 10 for compound descriptions.
Compounds followed by a dash in the percent mortality column were either not screened or had less than 80 mortality on the test species.

~0~37~

x~mple 8 Fall Armyworm Test units, each consisting of an 8-ounce plastic cup containing a layer of wheat germ diet, approxi~ately 0.5 cm thick, were prepared. Ten third-instar larvae of fall armyworm (Spodo~era fruaipe~~ were placed into each cup. Solutions of each of the test eolnpounds (acetone/distilled water 75/25 solvent) were sprayed onto the cups, a single solution per set of three cups. Spraying was accomplished by passing the cups, on a conveyer belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.5 pounds of active ingredient per acre (about 0.55 kg/ha) at 30 p.s.i.
The cups were then covered and held at 27C and 50%
relative humidity for 72 hours, after which time readings were taken. The results are tabulated below.
Compound ~Mort. Compound ~ Mort, Compound % ~ort.

1 100 15 1()0 29 100 2 100 16 1~)0 30 100 ~5 3 100 17 1~)0 31 9 100 23 100 37 1~0 13 100 27 100 sl 73 14 100 ~8 - 42 100 15~7~

46 ` 100 Bl 87 116 47 100 ~2 33 117 100 gol 100 125 63 60 g8 10~ 133 64 ~ 99 93 134 33 ; 65 - 100 60 135 ~ 25 66 100 101 - 136 : 67 100 102 - 137 : 6~ 100 103 - 138 33 71 40 . 106 100 1~1 -110 100 14~ -77 10~ 100 147 -1. Test procedure was identical to that described e~cept there was only one test cup.

~ , :

, 7~0 l'j2 163 - 19~ - 233 167 - 202 llD0 237 87 169 - 204 1~0 239 : 25 170 20 205 67 240 93 17~ 67 2].1 - 246 . ~
~`:..

~Og3.,~

258 ~0 Exampl~! 9 Tobacco ~udworm The test procedure of Example 8 was repeated for efficacy ayainst third-instar larvae of the tobacco budworm SHeliothis virescens) except that mortality was assessed at 48 hours. The results are tabulated below.

~ompound % Mort. Compound % Mort. Compound % Mort.

~ 100 16 100 24 13 ~6 100 61 ~0 96 28 ~7 63 0 98 100 3~ o 70 93 105 100 : 36 93 71 - 106 100 37 10~ 72 100 107 100 42 100 77 100 ~.12 - 120 - `

100 gol - 125 56 - 91 100 1~6 57 - 92 . 100 127 `
`' ' :``
' ' `.

;~ 7~1~

130 - 1~5 80 200 132 0 1~7 40 202 100 137 _ 172 27 ~07 33 139 - 17~ - 209 60 141 - 176 80 ~11 -144 ~0 179 73 214 1~5 - 180 - 215 147 _ 182 - 217 13 149 - 184 - 21g 150 - lB5 - 220 1~1 - 1~6 - 221 153 - 1~8 - 2Z3 : 154 - 189 - 224 ~: 155 - 190 53 225 158 - 193 - ~28 159 - 19~ 13 229 162 - lg7 _ 232 163 - 19~ - 233 . ':
:, " ,, :
~ .

4~

2~ 1 70 2~6 1~ 247 ~ 51 ~61 20~7~

~xample 10 Aster Le~hQ~per Test units were prepared from a series of 12-ounce cups, each containing oat (Aven~ sativa) seedlings in a l~inch layer of sterili~ed soil~ The test ~nits were sprayed with individual solutions of the below-listed compounds. After the oats had dried from being sprayed, between 10 and 15 adult aster leafhoppers (Mascrosteles fascifrons) were aspirated into each of the covered cups. The cups were held at 27C and 50% relative humidity for 48 hours, after which time mortality readings were taken. The following table depicts the activity of the compounds tested on aster leafhopper.

Ç~omPound % Mort. ~ompound ~~ Mort~ çompQ~n~ % ~ort.

8 - ~6 - ~4 9 100 27 - ~5 100 18 100 36 ~ 54 _ 901 _ 125 - 100 - 1~

20 7~ - 107 100 142 74 - 109 - 1~4 25 77 100 llZ - 197 79 71 llg - 149 30 ~2 - 117 - 152 86 - 1~1 - 156 35 87 - 12~ - 157 8~ 91 123 - 158 .

, ~ . -:

~CIl~ 7~

166 - 2~1 - 236 91 173 - 208 - 2q3 20 177 93 21~ 88 2~7 17~ 60 213 - 298 1~4 - 219 - 254 186 - 2~1 - 256 3~ 187 - 222 - 257 1~8 - 223 - 258 62 l91 - 226 - 261 :
., ~ ' . ~ . '.

)~7~C~

~xample 11 Southern Corn Ro~tworm Test units, each consisting of an 8-ounce plastic cup containing 1 sprouted corn seed, were prepared. Sets of three tests units were sprayed as described in E~ample 8 with individual solutions of the below-listed compounds. After the spray on the cups had dried, ive third-instar larvae of the southern corn rootworm (Dia~roti~a unde~imp~nctata howardi) were placed into each ~up. A moistened dental wick was inserted into each cup to prevent drying and the cups were then covered. The cups were then held at 27~C and 50% relative humidity for 48 hours, after which time mortality readings were taken. The results are tabulated below.

Compound ~_~Q~ Compound ~ Mort. compQ~n~ Q~

3 100 13 100 23 lOD

100 1~ 10~ 25 7 10~ 17 100 27 ~ 100 19 100 29 .

.

~3~7~Lal - 69 100 1~3 74 100 108 -l 00 41 100 75 . 67 109 lS 43 100 77 100 111 100 4~ 100 78 - 112 100 ~ 6 100 80 - 114 48 _ 82 100 116 Sl 100 85 - 119 52 - ~6 - 120 53 - 87 g3 121 ~; 55 100 89 100 123 56 _ gol _ 124 ~0 80 94 100 128 61 100 95 100 12g .~ . -~ .

z~
1&2 140 93 174 _ 208 100 144 100 178 1.00 212 100 146 - 180 100 Zlg 14~ 47 182 100 216 151 - 1~5 100 219 153 - 187 ~ 221 155 _ 189 100 223 : 162 - 196 - 230 :~ 163 - 197 - 231 :: lh4 93 198 - 232 : 35 165 100 1~9 _ 233 166 ~7 200 - 234 100 .~ ., , . , : . `
, L
i:

7~

15 2q7 25~57 93 ~61 2~ 7~

Example 12 Boll Weevil Five adult boll weevils (Anthonomus arandis were placed into each of a series of 9-ounce cups.
The test procedure employed was then otherwise the same as in Example 8 with three cups per treatment.
Mortality readings were taken 48 hours after treatment. The results are tabulated below.
Compound % Mort. Com~ound % Mort. Compound % Mort.

6 ~ 30 100 54 100 7 100 31 1~)0 55 100 34 1~0 58 12 1~0 36 8'7 60 21 100 45 ~3 69 93 ~, ~0~5~

73 87 10~ 100 143 100 60 110 ` 100 145 79 100114 ~ 149 0 83 10~118 - 153 20 gol _ 125 - 160 33 g4 100lZ9 - 164 73 25 95 10~130 - 165 100 99 100134 93 1~9 87 101 10013~ - 171 104 - 139 g7 174 35 lOS 100140 93 175 106 1001~1 93 176 100 ; , ,; ~
`

74~

17g ~ 214 - 2~9 182 ~7 217 - 252 100 1~4 - 219 - 254 100 185 ~7 220 - 255 93 lgl 100 226 - 261 193 100 228 ~ 263 1~5 _ 230 - 265 : 198 - 233 - 268 : 203 - 23a 205 lOQ ~40 93 209 100 2~4 21~ 93 245 27

Claims (23)

1. A compound of the formula wherein:
O is , , , , , , A is (CH2)t, O, S(O)q, NR7, OCH2 or S(O)qCH2, wherein, each carbon individually can be substituted with 1 to 2 substituents selected from 1 to 2 halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4-C7 alkylcycloalkyl, C2-C4 alkoxycarbonyl, or phenyl optionally substituted with 1 to 3 substituent independently selected from W;
R1 and R2 are independently R8, halogen, CN, NO2, N3, SCN, OR8, SR8, SOR8, SO2R8, NR8R9, C(O)R8, CO2R8, C(O)NR8R9, OC(O)R8, OCO2R8, OC(O)NR8R9, NR9C(O)R8, NR9C(O)NR8R9, OSO2R8, NR9SO2R8, or when m is 2, R1 is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O OR CH2CH2O

each of which is optionally substituted with 1 to 4 halogen atoms or 1 to 2 methyl groups, or when n is 2, R2 is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O or CH2CH2O
each of which can be substituted 1 to 4 halogens or 1 to 2 methyl groups; R2 being other than CH3 when R1, R3 and R4 are H and A is CH2;
R3 is H, C1-C6 alkyl, C1-C6 haloalkyl, C4-C6 alkylcycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 cyanoalkyl, C3-C8 alkoxycarbonylalkyl, OR8, S(O)qR8, NR8R9, CN, CO2R8, C(O)R8, C(O)NR8R9, C(S)NR8R9, C(S)R8, C(S)SR8, phenyl optionally substituted with (R10)p or benzyl optionally substituted with 1 to 3 substituents independently selected from W
or R3 is C3-C6 cycloalkyl optionally substituted with 1 to 2 halogens or 1 to 2 CH3;
R4 is H, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 cyanoalkyl, phenyl optionally substituted with (R10)p or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R5 and R6 are independently H, C1-C22 alkyl, C2-C22 alkoxyalkyl, C2-C22 alkylcarbonyl, C2-C22 alkoxycarbonyl, C2-C22 haloalkyl carbonyl, C2-C22 haloalkoxycarbonyl, SR11, CHO, C1-C4 alkylsulfonyl, phenylsulfonyl optionally substituted with 1 to 3 substituents independently selected from W;
C7-C15 phenoxycarbonyl optionally substituted with 1 to 3 substituents selected from W; C7-C15 phenylcarbonyl optionally substituted with 1 to 3 substituents independently selected from W;
C(O)CO2C1 to C4 alkyl, C8-C12 benzyloxycarbonyl optionally substituted with 1 to 3 substituents independently selected from W; or R5 and R6 are independently phenyl optionally substituted with 1 to 3 substituents independently selected from W, or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R7 is H, C1-C9 alkyl or phenyl optionally substituted with W; SR8, SOR8, SO2R8, C(O)R8, CO2R8, C(O)NR8R9, C(S)NR8R9, C(S)R8, C(S)OR8, P(O)(OR8)2, P(S)(OR8)2, p(O)(R3)OR8 or P(O)(R8)SR8; provided that when R7 is other than COR8, C(O))NR8R9 or C(S)NR8R9 then R8 is other than H;
R8 is H, C1-C6 alkyl, C1-C6 haloalkyl, C4-C7 cycloalkylalkyl, C4-C7 halocycloalkylalkyl C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C2-C6 alkoxyalkyl, C2-C6 alkylthioalkyl, C1-C6 nitroalkyl, C2-C6 cyanoalkyl, C3-C8 alkoxycarbonylalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, phenyl optionally substituted with 1 to 3 substituents independently selected from W

or benzyl optionally substituted with 1 to 3 substituents independently selected from W;
R9 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, or R8 and R9 is optionally taken together as (CH2)4, (CH2)5 or (CH2CH2OCH2CH2);
R10 is R8, halogen, CN, NO2, N3, SCN, OR8, SR8, SOR8, SO2R8, NR8R9, COR8, CO2R8, CONR8R9, SO2NR8R9, OC(O)R8, OCO2R8, OC(O)NR8R9, NR9C(O)R8, NR9C(O)NR8R9, OSO2R8, NR9SO2R8 or when p is 2, R10 is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O, or CH2CH2O each of which is optionally substituted with independently, 1 to 4 halogen atoms or 1 to
2 methyl groups;
R11 is C1-C22 alkyl, C1-C22 haloalkyl, phenyl optionally substituted with 1 to 3 substituents independently selected from W, or R11 is NR12C(O)R13, NR12S(O)aR13, C(O)R13, NR12R16, SR14, , or ;

R12 and R16 are independently selected from C1 -C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, C2-C6 cyanoalkyl, C2-C6 alkoxyalkyl, C3-C8 alkoxycarbonylalkyl, C4-C8 dialkylaminocarbonylalkyl, phenyl optionally substituted by 1 to 2 substituents selected from W, benzyl optionally substituted by 1 to 2 substituents selected from W and phenethyl optionally substituted by 1 to 2 substituents selected from W, or R12-R16 is optionally taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2, each ring optionally substituted with 1 to 2 CH3;
R13 is F, C1-C20 alkyl, C1-C6 haloalkyl, C2-C8 dialkylamino, piperidenyl, pyrrol-idenyl, morpholinyl, phenyl optionally sub-stituted with 1 to 3 substituents selected from W, or R13 is C1-C20 alkoxy C1-C6 haloalkoxy or C1-C4 alkoxy substituted with cyano, nitro, C1-C4 alkoxy, C4-C8 alkoxyalkoxy, C1-C2 alkylthio, C2-C3 alkoxycarbonyl, C3-C5 dialkylaminocarbonyl or phenyl optionally substituted with 1 to 3 substituents independently selected from W, or R13 is phenoxy optionally substituted with 1 to 3 substituents selected from W;
R14 and R15 are independently selected from C1-C9 alkyl, C2-C4 haloalkyl, phenyl optionally substituted with 1 to 3 substi-tuents independently selected from W or R14 and R15 is optionally taken together as (CH2)2, (CH2)3 or CH2C(CH3)2CH2;
W is halogen, CN, NO2, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, Cl-C2 haloalkoxy, Cl-C2 alkylthio, C1-C2 haloalkylthio, C1-C2 alkylsulfonyl or C1-C2 haloalkylsulfonyl;
m is 1 to 5;
n is 1 to 4;
t is 0 to 3;
q is 0 to 2;
p is 1 to 3;
a is 0 to 2;
V is O or S;
X is O or S;

Y is O or S; and Z is O or S.

2. A compound according to Claim 1 wherein:
when R3 or R4 is H and A is oxygen then the remainins R3 or R4 is other than phenyl or phenyl optionally substituted with W and when t is 0 then R3 or R4 are other than Ph or phenyl optionally substituted with w.
3. A compound according to Claim 1 wherein:
R1, R2 and R10 are R8, halogen, CN, NO2, OR8, SR8, SOR8, SO2R8, NR8Rg, CO2R8, SO2NR8R9, or when m, n or q is 2, then R1, R2 or R10 respectively is optionally taken together to form a 5 or 6 membered fused ring as OCH2O, OCH2CH2O or CH2CH2O each of which is optionally substituted with 1 to 4 halogens or 1 to 2 methyl groups;
R8 is H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkylalkyl, C3-C6 halo-cycloalkylalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, phenyl optionally substituted with 1 to 2 substituents independently selected from W or benzyl optionally substituted with 1 to 2 substituents independently selected from W;
R5 and R6 are independently H, C1-C3 alkyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, CHO, SR11, phenyl optionally substituted with 1 to 2 substituents independently selected from W, or benzyl optionally substituted with 1 to 2 substituents independently selected from W;
R11 is C1-C3 alkyl, phenyl optionally substituted with 1 to 2 substituents independently selected from W, NR12C(O)R13, NR12S(O)aR13, C(O)R13, NR12R16;

or .

R12 and R16 are independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C5-C6 cycloalkyl, C3-C8 alkoxycarbonyl- alkyl, phenyl, benzyl and phenethyl or each phenyl, benzyl and phenethyl optionally substituted with 1 to 2 substituents independently selected from W, or R12 and R16 can be taken together as (CH2)4, (CH2)5 or (CH2)2O(CH2)2;
R14 and R15 are independently selected from C1 to C3 alkyl or phenyl;
m is 1 to 2;
n is 1 to 2;
p is 1 to 2;
q is 0 V is S; and a is 2.
4. A compound according to Claim 3 wherein:
R3 is H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, CN, phenyl optionally substituted with (R10)p or benzyl optionally substituted with 1 to 2 substituents independently selected from W;
R4 is H, C1-C3 alkyl, C3-C4 alkenyl or C3-C4 alkynyl;
R5 is H, Me, CO2Me, CO2Et, SR11 or phenyl optionally substituted with 1 to 2 sub-stituents independently selected from W;
R6 is H, Me, C(O)Me, CO2Me or SR11;
R11 is C1-C3 alkyl, NR12C(O)R13, NR12S(O)aR13, C(O)R13, or phenyl optionally substituted with C1, NO2 or CH3;
R12 is C1-C4 alkyl or phenyl optionally substituted with C1 or CH3;
R13 is C1-C12 alkyl, C1-C12 alkoxy, C1-C6 haloalkyl, dimethylamino, phenyl optionally substituted with C1 or CH3, or R13 is C1-C4 alkoxy substituted with C2-C4 alkoxy or 1 to 6 halogens;
A is CH2, CH2CH2, O, S, OCH2, NR7 or SCH2, wherein, each carbon is optionally substituted with C1-C3 alkyl or phenyl, wherein, the phenyl is optionally substituted with W; and;
R7 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl or C1-C4 alkylsulfonyl.
5. A compound according to Claim 4 wherein:
R1 and R2 are independently selected from F, C1, Br, CN, NO2, OMe, CF3, OCF2H, OCF2CF2H, SMe, SO2Me, SCF2H or when m or n is 2 R1 or R2 respectively is optionally taken together as CH2C(CH3)2O
or CF2CF2O;

R3 is C1 to C4 alkyl, allyl, propargyl, or phenyl optionally substituted with F, C1, Br, CF3, OCF2H, OCF3, SCF2H, CN, NO2, CH3, OMe or CO2Me;
R4 is H or CH3;
R5 is H, CH3 CO2CH3, CO2Et, or phenyl optionally substituted with F or C1;
R6 is H, CH3, C(O)CH3 or CO2CH3; and A is O, S or CH2, optionally substituted with C1-C3 alkyl or phenyl which may also be optionally substituted with W.
6. A compound according to Claim 5 wherein:
A is CH2; and R3 is optionally substituted phenyl or C1 to C4 alkyl.
7. A compound according to Claim 6 wherein Q
is Q-1.
8. A compound according to Claim 1 wherein Q
is Q-1.
9. A compound according to Claim 1 wherein Q
is Q-2.
10. A compound according to Claim 1 wherein Q
is Q-3.
11. A compound according to Claim 1 wherein Q
is Q-4.
12. A compound according to Claim 1 wherein Q
is Q-5.
13. A compound according to Claim 1 wherein Q
is Q-6.
14. A compound according to Claim 1 wherein Q
is Q-7.
15. A compound according to Claim 1 wherein Q
is Q-8.
16. A compound according to Claim 7:
2-[5-fluoro-2-(4-fluorophenyl)-2,3-dihydro-lH-inden-l-yl-idene]-N-[4-(trifluoromethoxy)phenyl]hydrazine carboxamide.
17. A compound according to Claim 5:
2-[6-chloro-2,3-dihydro-2-methyl-2-(2-propenyl)-3-benzo-furanylidene]-N-[4-(trifluoromethoxy)phenyl]hydrazine carboxamide.
18. A compound according to Claim 7:
2-(5-fluoro-2,3-dihydro-2-methyl -lH-inden-l-ylidene)-N-[4-(trifluoro methyl)phenyl]hydrazine carboxamide.
19. A compound according to Claim 7:
2-[5-chloro-2,3-dihydro-2-(1-methylethyl) -lH-inden-l-ylidene]-N-[4-(trifluoro-methyl)phenyl]hydrazine carboxamide.
20. A compound according to Claim 7:
2-(5-chloro-2,3-dihydro-2-methyl-lH
-inden-l-ylidene)-N-[4-(trifluoromethyl) phenyl]hydrazine carboxamide.
21. A compound according to Claim 7:
2-[5-fluoro-2-(4-fluorophenyl)-2,3-dihydro -lH-inden-l-yl-idene]-N-[4-(trifluoro-methyl)phenyl]hydrazine carboxamide.
22. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound according to Claim 1 and a carrier therefor.
23. A method for controlling arthropods comprising applying to them or to their environment an arthropodicidally effective amount of a compound according to Claim 1.
CA 2005740 1988-12-27 1989-12-15 Substituted semicarbazone arthropodicides Abandoned CA2005740A1 (en)

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US290404 1988-12-27

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MX (1) MX18911A (en)
ZA (1) ZA899916B (en)

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AU2002952453A0 (en) * 2002-11-01 2002-11-21 Novogen Research Pty Ltd Aminated isoflavonoid derivatives and uses thereof
JP4532339B2 (en) * 2005-05-18 2010-08-25 アグロカネショウ株式会社 Trifluoromethylsulfonylamidine derivatives effective for pest control

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GT198900079A (en) 1991-06-19

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