DE2040580A1 - Thiazole derivatives - Google Patents

Description

Dr. F Zumstein sen. - Dr. E. Assmann Dr. R. Koenigsbsrger - Dipl. Phys. R. Holzbauer

Dr. V. Zumstein jun.

Patent attorneys

8 Mönchen 2, Bräuhaunstrasse 4 / lH

Case 646/660

MAY & BAKER LIMITED, Dagenham, Essex, England

Thiazole derivatives

The present invention relates to new thiazole derivatives, processes for their preparation, herbicidal compositions containing them and their use as herbicides.

It is known, for example, from British patent specification 1,131 and French patent specification 1,533,184 that
Thiazole derivatives of the general formula

I ι

NCN R ₁

(in which X and Y, _o the same or different from each other can, in each case a hydrogen or halogen atom or a nitro, J £ thiocyanate, cyano, carboxyl, alkoxycarbonyl, amino, hydroxyl,

- ¹ hydroxyalkyl, C ^^ - alkyl, C _{le> 2} j.- ^{Alk: ox} y ~ * C ^^ - haloalkyl, ^ Ci /, - haloalkoxy, aryl, halogenated aryl, alkylaryl,

^, Alkoxyaryl, halogenated alkylaryl, halogenated'alkoxyaryl,

^ Aryloxy, halogenated aryloxy, nitroaryloxy or alkylaryl

20A0580

Oxy group, Z represents an oxygen or sulfur atom, R ^ a hydrogen atom or an alkyl, alkoxy, alkenyl, alkenoxy or alkynyl group with 1-4 carbon atoms or an alkyl acyl, halogenated alkyl acyl, arylacyl, halogenated Arylacyl, alkylarylacyl or alkoxyarylacyl group and each of the radicals R ₂ and R, a hydrogen atom or an alkyl, alkoxy, alkenyl, alkenoxy or alkynyl group with 1-4 carbon atoms or an alkylaryl, halogenated alkylaryl, aryl , represents halogenated aryl, aryloxy or halogenated aryloxy groups, provided that R ₂ and R- are not hydrogen in the same compound at the same time), have valuable herbicidal properties, especially for inhibiting growth or destroying various foreign plants, such as grasses, shrubbery, and undesirable undergrowth are useful. The thiazole derivatives of the general formula I can be used as total herbicides, selective herbicides and growth regulators. They can be used before sowing or planting the crops or after sowing but before the crops or weeds have grown as a pre-emergence treatment, or they can also be used after growing as a post-emergence treatment emergence). A dosage range which has been given for the use of the thiazole derivatives of the general formula I as herbicides is 0.1 kg to J> 0 kg per hectare (0.09 lbs to 27 lbs per acre) and preferably 0.5 kg to 20 kg per hectare (0.45 lbs to 18 lbs per acre). Some of the compounds of general formula I have been stated to have a considerable persistence in their effectiveness as herbicides for a period of time from several weeks to several months.

It has now been found that a very narrow class of thiazole derivatives, which have not yet been mentioned, but in the broad class of compounds of the general formula I, such as it has been defined above fall, eminently valuable properties as herbicides, being much more effective than herbicides at lower, more economically acceptable Application quantities are as chemically closely related compounds,

109817/2227

those specifically in the above British and French Patent specification and chemically closely related compounds, which fall within the scope of the UK and French patents cited above, but not specifically * there and other chemically closely related compounds.

The previously unknown thiazole derivatives are according to the invention the general formula

II

created in which X ^ is a chlorine, bromine or iodine atom, R ^ is a methyl or ethyl group, R ₁ - is a hydrogen atom or a methyl group and Rg is a methyl group or, if R ₂ , and R, - each one Means methyl group, also represents an ethyl or n-propy group, as well as their acid addition salts. Preferably, Rj ^ and Rg each represents a methyl group, and Rr represents a hydrogen atom or a methyl group _o

The results obtained at under comparable conditions Tests of the herbicidal properties of the compounds of the formula II in comparison to compounds of the formula I were obtained are in the following Tables I, II and III specified. The following test procedures were used:

(a) Contact application (Foliar application, i.e. application on the foliage).

Weeds at the stage of seedlings in pots in the greenhouse were drawn with solutions of the compounds to be tested in aqueous acetone (according to British Pharmacopoeia) injected. The number of seedling plants from each

1098 17/2227

species sprayed was 5 in the case of broad-leaved plants, about 30 in the case of Avena fatua and about 100 im Case of Alopecurus myosuroides and Poa annua. A corresponding Numbers of seedlings of each species were sprayed with aqueous acetone alone as a control group. The concentrations of the thiazole derivatives in the solutions were chosen so that they correspond to the practical use levels corresponded, starting from a minimal amount from 0.14 kg per hectare (0.125 lbs per acre) and by one Factor of two geometrically increasing up to a maximum amount of 8.97 kg per hectare (8 lbs per acre) applied in 506 1 spray liquid per hectare (45 gallons per acre). The application was carried out by means of a laboratory precision spray device, which was previously calibrated to deliver this volume. The plants were then grown in a greenhouse under standard conditions for 20 to 30 days Maintained under normal watering for temperature and length of day from the day after spraying. Herbicidal effectiveness was 20 to 30 days for each species for each application dose for each compound visually assessed and the minimum herbicidally effective dose, i.e., the dose which results in a 90% kill, was determined expressed for each species.

(b) Residual (soil) activity or permanent (soil) effect (sterilized soil)

Weed seeds were grown on the surface of sterilized soil (John Innes No. 1 Potting Composition) which was found in small pots sown, one pot for each species being used for each treatment. The ones to be examined

aqueous compounds were ground and in solutions in acetone the uncovered seeds using a laboratory precision sprayer, which was calibrated to deliver 506 liters of spray solution per hectare (45 gallons per acre), in concentrations applied, the practical application amounts of 0.14, 0.28, 0.56, 1.12, 2.24, 4.48 and 8.97 kg per hectare

1098 1 7 / ?? 27

(0.125, 0.25, 0.5. »1> 2, 4 and 8 lbs per acre). One set of pots was sprayed with acetone just to serve as To serve comparison control. The seeds were then covered with sand and under standard temperature conditions kept in the greenhouse under normal watering from the day after spraying. After 20 to 30 days in the greenhouse a visual assessment was made of the minimum application amount for each test compound required to a 90 # or greater reduction in the growth of everyone To give weed species in comparison with the controls (minimum herbicidally effective dose - MED). .

(c) Residual (soil) activity: comparison of the activity in sterilized and non-sterilized soil

The test procedure described under (b) above was used with the exception that the seeds were sprayed with Soil were covered. "Each test compound was applied to two sets of pots, one set of John Innes No." I Potting Compost (sterilized soil) and the other contained Kettering Loam (unsterilized soil).

(d) residual soil activity: determination; the ED9O

Some species (indicated by asterisk in Table III) were sown in small pots in Kettering Loam and covered with Kettering Loam, one pot for each species being used for each treatment. The compounds were applied as under (b) Xn concentrations, the practical application amounts of 0.14, 0.28, 0.56, 1.12, 2.24 and 4.48 kg per hectare (0.125, 0.25, 0 , 5 * .1 * 2 and 4 lbs per acre). After 28 to 30 days in the greenhouse, the above-ground parts of the plants were cut off and freshly weighed, and the reduction in growth caused by each application amount was calculated as a percentage based on untreated control plants. The doses that show a 90 # reduction in growth compared with untreated

109817/2227

Control plants (ED9O) were then graphed out obtained a log-probit curve of the dosage response.

(The MED is a visual assessment of the ED9O, and the two Values are comparable. The difference is made for the sake of accuracy).

In the results given in Tables I, II and III below, the symbols have the following meanings:

* (I) "NR" means that no significant herbicidal activity at the applied highest dose d ^Q r test compound [8.97 kg per hectare (8 pounds per acre)] could be detected.

(ii) "-" means the test compound in question has not been tested against the respective special plant species.

(iii) A number preceded by ">" means that significantly less than $ 90 kill was obtained at the dose used, which was the highest tested (taking into account the assumed statistical interpretation of this

) Number for the number of plants grown in a corresponding manner treated).

(iv) a number preceded by "^" means a low one Reduced growth was caused at that application dose, which was the highest dose tested.

(v) In a number of cases the kill of a species obtained was slightly less than 90 % _{for a particular application dose} while a complete kill was obtained at the next higher application dose. In this case the minimum herbicidally effective dose was expressed as being between these two application doses, for example "1 to 2" lbs per acre (1.12 to 2.24 kg per hectare).

, 109817/2227

(vi) the symbol "s" means complete kill was obtained at this application dose, which was the lowest dose tested.

In these tests there was no significant difference between the controls sprayed with aqueous acetone

and sprayed plants under the same conditions grew to be noted.

With the results shown in the following tables Ϊ, Il and III are indicated, the various substituents are on the thiazolylurea according to the general formula

III

identified.

It should be noted that the above formula is a general formula for the compounds of general formula II and certain of the classes of compounds of the general formula I which are closely related to the compounds of the formula II, and that the corresponding Transfers in the identification of the symbols for the identification of the individual connections when used the definitions of formulas I and II must be made.

1098 17/222

TABLE ί Ι

(Continuation

Contact and residual (sterilized soil) activity of compounds of the invention

• Connection 'Il Substituents H ⁸ . S ⁹ Me Hg Hey H R ¹⁰ Z ² ... . · 'Σ R? Me H Me Tt Hey H , H UP O IA Me j He J H Hey H ₃ II ι a 3r cn T.B Me rie K: ti Br CO '2 Me Ms ti a Cl ^{1st ;} O p Me At ι Hq H E. J / 4- ^; Ät lie Hs H Br- 5 At 8 S Mon Hey H * C.1. 6th 9 MG E. J 7th 4?
12 y lie t me PI Br Ke I At J Hs j He ^r ü Cl H! He λ i__Er E! Br

Compound IA is the hydrobromide acetate of compound 1 Compound 13 is the kydrobromide of compound 1

from rush J

Contact »and residual sterilized earth) activity of inventive compounds

1 B. r-1 Minimal effective 1 R. 03 CQ •H CO cn CO cn 5 25th co co dose CQ ω Lb / acre ϊ CQ • Η co co Earth) co J - " < ι CO Contact (Foliar) Activity •H S. •H 03 •H • Η •H 0.125 ■ 2 ρ S. ! 3 • Η CQ • Η co 1A • Η •H P. Ö Sh O in ω -P U • Η Residual (soil) activity P. Ö ο ZS 0.25 !? =? 1B I-t -P r-l CO OJ CO Tt co ω 1- 5-1 co 03 S. O (sterilized CO ω CO Ό -P β 2 O cn O ö f> O O S. 2 O Century Si! O O co co IT P. P. •H U •H β ■ Η -Pj (D co • Η • Η Ö «Η ta 3 O • 3 cn CQ co in • Η Φ 2 P. CQ to CO jL | • Η cc ö C. <0.125 ' Ö H -p -P O O CQ -P co ο •H 4th O) O CO CQ r-4 κ * 3 ■ ö CO Ph , Q Yes CO, 125 t> r <0, «Aj co CD J_l 5 O <O, 125 125 0.5-1 ί> I.
I. O) 5 <O, 125 , - I O, CO <$ I. }> · 7th O <O _? 125 O, 125-
25th 1 O 8th <O _? 125 Ph O, 5-1 0.5-1 PM tj ©, 125 <O, 125 -Pj 125- 1 <Ο, 125 10 <O, 125 ' 0.125 <0.125 <0, 25th <0.125 Tt ^! 0.125- 0.125 125 1 0.125 0.125 0.25 <O, 125 <O, 125 O, 0.125 <0.125 40.125 <O, 125 40.125 0.125- O, 25- 1-2 ■ 0.125 0.125- 0.125 <O _f 125 <0.125 0.25 5 0.125 0.25 «0.125 0.125- 0.125 0 _r 5-1 1 0.125 0.125 iö, T25 0.25 40.125 O, 0.5-1 0.25 0.125- 0.25 € 0.125 0.5 1 0.5-1 0.25 · <Ο, Τ25 0.25 0.125 0.25 O _? 25th 1 0.5-1 <O, 125 0.5 0.125- 12 Γ 0.125 0.125 0.5 1 0.5 <Ο, 125 0.25 1 RO, 125 0.25 0.25 4th 0.5 0.125 1 ^π , 125 0.5 0.25 0.125 <0.125 1-2 0.25 0.25 0.25 0.5 0.5 1.0 0.125 0.125 4th 0.5 0.25 0.125 <0.12 5 0.5-1 0 ₉ 25 <0.125 <0.12 5 0.25 <Oi125 0.5 ι 0.5 40.125 2 2 ■ 0.125 0.25 <0.125 0.5 ^: -.0.25- - 0.125 1 0.5 0.125 0.25 4th 1 1-2 0.25 0.25 2 0.25 1-2 0.25 0.12l ^ · Ü 0.5-1 0.5 4th 0.5.S 0.5 0.25 0.5 0.25 2 0.125 0.25-
0.5 4th CO, 125 4th 2 0.25 0.5 4-8 0.25 0.5-1 0.125 1 0.5 1-2

Compound IA is the hydrobromide ace.tat of compound 1
Compound ΊΒ is the hydrobromide of compound 1

TABLE II

(Continuation

Contact and residual (sterilized soil) activity of compounds of general formula I.

Substituents E ⁸ E? E ¹⁰ - χ ² link E?
ι
. ,. ., .., " Hey H K H Γ
i
13th H ^! ° 6 ^Η 5 H Ξ H 14th H Hey H TT Ed TT
Γ * Hey H υ
XJ. Cl 16 H : Hey Hey JT Cl ι ¹⁷ , ττ
Γρ Hey Hey H Br 18th H Hey: Ξ PIe ' Ή 19th ττ Me; H - 3 J-T 20th ι
^η Hey: F. Hey Ci I 21 -T

He: i He I He Cl

TABEL

II

Contact and residual (sterilized soil) activity of compounds of general formula I.

effective dose lb / acre

,..Contact-. (Foliar) activity

¹ S • rl a u

13 "Ϊ4

15th

> 8

NH

2-4

^ 125

• Η HO

0.125

CQ

CQ

CO

4-8

4-8

ti

ΓϊΗ

4-8

<Ο, 125

<0.125

CD

H H O

> 8

0.25-

CQ

4-8

NS

CTj

MR

"Residual - (soil) acti vTfät" (sterilized earth) ''"

TÜ8

'CQ

4-8

0.125-0.25

cdi
-H

•H

RJ

NO

0.125

cö

1 a

> 8

NO

4-8

0.25-0.5

17th

0.25

0.5

0.25

0.25

0.25-0 _? 5

0.5

o, 5

0.25-

o, 5

18th

<0.125

<0.125

<0.125

<Ο, 125

0.125-0 _? 25; 0.125

0.125

19th

1-2

4-8

> 8

4-8

; 4-8

4-8

> 8

> 8

20th

j21

i- 122

<0.125

0.125 <O _? 125

o _? 5

<0 _? $ 12

.4-8

0.5

2r4.

0.5

4-8

4-8

TABLE II (1st continuation) (Continued 4)

Substituents 0 R ⁷ R ⁸ H ⁹ η ¹⁰ X ² χ} • Η , η U Q) 23 Me »Le H Me Br 24 H Me H Me Br 25th η-Pr Me ¹ H. H Br 26th η-Pr Me H H J 27 Lso-Pr Me H H Br 28 Lso-Pr Me H H Cl 29 l-Bu Me H H Br 30th l-Bu Me H H Cl 31 LSO-Bu Me H H Br 32 jec-Bu Me H H Br 33 sec-Bu Me H H J 34 Me Et H H Br

109817/2227

4 *

ro

ro

ro

00

00

ro I

ro

00

OO

VJD

00

te!

00

00

co)

oo

00

oo

fei

ftf

oo

ro

U!

Ul

V> J

Ul

OO

Ut ro

Ul

ro

Ul

OO

ro - »ui ro

Ul

ro

ro

ro

Ul

ro

link

Chenopodium

album

Polygpnum

lapathifolium

Si.napls

arvensis

Matrioaria
inodora

Stellaria
media

Avena
fatua

Alopecurus

myosuroides

Poa annua

Sinapis
arvensis

Matricaria
inodora

Avena fatua

Poa annua

ο P-.

C +

CD
fV c + I

H-05
4th

>
■ PT
c + H * <JH * c +

3 H

CO CD

H-

4 PT

01 03

S-

CD

U O

ro

H-

co

O 4

CD

H-W

cd: cd

c + CQ
H-

m js

H- 03
CD H
4 I.

Η ^ -ν

Hbd

H- O
OJ Cii
H-CD
CD P
4 I.
H- ^
CD fo
PT

CD H-

1-3

H H

O 4 H- 01 CD ΗΝ C

N • Ρ (UW ■ Ρ f-. O

Substituents ■ j % H
O U
PQ W. ri
O U
W. W. W. rq H
O N ί-ι
W. O
H
W. W. MJ W. H! W. &
O-
W.
• rl W.
• P W. Ä
Ä M. W. Ix! ο
H
O
O
to rilf-l
ο ω
U
Ph ■ nt ίχ? G)
a OJ ¹⁰ M __ 4-5
*?: _ C)
«—I
(D
ΗΛ C) Al
O
ω
• Η Ä
O
ta
• Η -? Λ <?
Ρ! " u ^ PI - <U CN S. ω r-l ο SunpufqjsA LfN
IA co IA tA

109817/2227

TABLE ΪΙ (2nd port setting)

.Link. ... . _ Minimum effective dose Ib / acre. Ä
O
i
€ album 1 1-2 I.
la
pi _r q
r - ίι Ph
P-ijrH 1"
Ki] C)
I. CD
•H
ü
Ή
4- *
S. inodora
- r-ij d
-p | O
approx! S. cüjc3 | .. ' _nl ö3i
gjo |
^ O! Pj §!
^ i!
: · ^D | I.
■ ^ ^! i HH I 8 1 Residual (soil) activity
(sterilized earth) " cdi cd
Ο | Η
Do _or ° to
4th CtJ
I. I.
] 55 Contact (political) activity 56 i 1
t 2 4: > 8 8th 2-4 4-8 2 CO
• p | §
II
OD ¹ IkJ ί
j
j
j
ί 57 > 2 ' 4th 4th HE ! i * IH j ITR . 8th 8th j 1-2 · 8th 4th 58 <0> 125 8th 4th 3SE 4th KH ^Ί 3SiE I. 8
I. > 8 ■ »8 ί 8 ' 1-2 4th > 8 > 8 59 <0 _? 125 8th 4th KH : 8th KR St. SE ι SE j 4-8 4th "8th 8th 40 1 8th 8th ΪΤΗ KH KH 4th > 8 bra JiH I.
i
j 41
j 1-2 8th 8th 4th 8th ^8th 4th > 8 2-4 42 2 2 2 8th 8th > 8 j O 1 2 1 45 IiH "2 2 IiH .8th" "8th ό, 5 · 1-2 4th 1-2 - 44 4th 4th ■ 3S2 j 2 > 8. . I ¹ EH 3SE 3STR 45 4th 2-4 2-4
t 8th ITR .MR > 8 > δ
S. 3SE ITR BRA- 2TH IiH ! ί ί ITH ITR 3SS 4th FR !! TqH I
It 4th ;> 8 ITR - ITR '.

TABLE II (3rd continuation) (Continuation

Substituents

in

: ί

bO.

¹ ^ -, ■ C- i

U9

I ι

46 j Ke t-bu XT
YY H Cl 4-7 I.
Hey sec-Bu ^H Ξ Br 4-8 Ke sec-Bu j 49 Ke Allyl H 50 Ke A.llr / 1 E. H i
j 51 n-Pr H ■
H Sr 52 Me iso-Pr iso-
Pr H He 53 Ke n-Pr n-Pr H Br C / ι
> - '■ Ke Allyl Ke. H ■ Br 1
55 y Hey n-Bu Ke K ■ Br 56 lie iso-Pr Ke -τ Br 57 Ns iso ~ Pr ^H j \

INJ

O Ol OD

TABLE Ii (3rd continuation)

Minimum effective dose Ib / acre

Contact (Foliar) Activity

Residual (soil) activi (sterilized soil)

Ο · 'Γ;

COj

CIi-Hi •H; C3 |

SM

cdi fei

• n

Sicöj

• HI OJ

-P]

^ rf

• Η

■ —Il c3

t-i'rri

COj

11

O \ U
O

ol ρ

r-i

C2

K-Hi
• H C0 |

φι

• HO

etc.

li-sl

Yes

CD

egg

CO

3SB

ISH

> 8 IL_ ™ _J

IiR

> 8 {j 4-8

> 8

3SR

> s

Tf

Room

> 8

1-2

4-8

1-2 4-8

ι-;

1-2

O,

> 8

0.5

SaR

"3SS

SIi KR

KR

> 8

<0 _f 125

> 8

"8th

KR

ITH

0.5

4-8

KR

> 8 kr

0.5-1 Ij 'KR ".. KR

-U, ■ "

25th

IiR

<O, 125

0 _? 125 2-4

1-2

0.25 yr

1-2 [Ι Q ₇ 25

0 _? 5 ~ l

0> 5

<0 _? 125-

TABLE II (4th continuation)

(Continuation

co KJ

link Subscribers Ke H ^S Ät _H io P-Cl- ο. 58 No Ät Ke : i H Br 59 n-Bu Ke Ke H Br 50 Ke Ke H H 3r j 61 H E. H H 3r 52 Ke H 11 — Fz * Ξ 3r 53 Ke H J 64 Ke Ät Ät j κ Cl 65 Ben-
207I Ke Ke 55 Ks Ke XT

TABLE II (4th continuation)

Minimum effective dose Ib / acre

Ii. Contact - (FoIi ar -) ac t i vi t ät . · Residual (soil) activated (sterilized Earth) _ did

faD

¹ S Xt

3: 3!

α οι

at

• n

r-j r — ϊ

ti

III

= 11

rf

0.25

ITR

> 8

■ 2

4-8

•SO

bi

> 8

> 8

SfR

ΉΡ,

"8th

4-8

4-8

> 8

> 8

4-8

4-8

> 8

fairy

0.125

<0 _? 125

4-8

> 8 ISR

> P

4-8

4-8

<0.125

KR

KR

KR

KR

KR

IiR

KR

KR

KR

KB

FR

KR

2-4

, ij.

"8th

KR

TABLE II ( 5th continuation)

O CD CO

ro

2 O

Substituents

; ι

link Allyl Hey Ke H ⁹ " I Me ^Η _Ε ιο X ²
I. 67 cnyl " i
H Ät TT Γ H Cl 63 Prop Ke Me H TT H 69
! 70. lie Cy el c- H ZT Cl 71 H
I. Jr-o-
teariryl Hey ί
Br 72 _: i y n-pr H Br 73; iii-? r H Br JT Br ίΚ
ι Br I.
I. I.
Br

(Continuation

κ The connections

and 75 are thioureas, i.e. compound 74 is l- (5-bromothiazol-2-yl) -3-

methy! thiourea "

Compound 75 is l- (5-3romthiazol-2-yl-l, J- : dimethy! thiourea

- EM
Ii
"oj.
I.
üj'rö r-i Contact- (F > Ö pi ® 1 A. BEL L-E II inodora. ! 2-4 ■ 4 (5th port. COiO
ojp setting) Poa annua ■
■
■ 4-3 Residual (soil) activity
■ (sterilized earth) τι!
Sj ö
r \ 1 Γι
<^; · -.
■ p | o 1
oil·
CDi
> :! Poa annua ' Link 8th ■ ^: Minimum > 8 j '2 ■ in effective dose i.
OQ ί ti 3 ' 8th 57 "8th oliar) activity * _ , 8th . 4th 2LR 4-8 "8th 4-S
I. 68 8th I.
"T" i
f,
-P "m 4-3, θί-P
i> J _- CtJ KH ' lb / acre ² : δ . .8th > 8 69 1-2 0/25 4th 4th SH ^!
i 2 I> 8. “S. 4th 4th 70 0.25 2-4 > 8 8th ■ 8th ■ ! 2-4
r ■ 2 2 - 2 71 ! 2 4th > 8 1 in the 1-2 72 ITH ^m 4-3. j i-2
ι .NH ITH 73 4th 3 > 3 ISE 2 KH " 4th > 8 74 ^K 4-8 S. 0.5-1 > 3 8th ! ^δ ·.
» 2 4th 2 75 * 2 2 SH ' > 8 2 WR o. 5-1 1 . I 2 m 2 ITR > s - 1-2 "8th • 1-2

Compounds 74 and 75 are thioureas, i.e. compound 74 is 1- (5-3romthiazol-2-yI) -5-

methy! thiourea ''

: ■ Compound 75 is l- (5-bromothiazol-2-yi) -l, 5 ·

■■. . ' dimethy! thiourea

TABLE III

(Continuation

Comparison of residual activity in sterilized soil (John Innes Potting Composition) and natural unsterilized soil (Kettering Loam) (A) from compounds of Tables I and (B) Compounds of Table II showing significant residual activity in sterilized soil

("JIP" = John Innes No. 1 potting composition and "KL" = Kettering Loam) * = ^ED 90

ro ro ro

■ p.? Substituents E? E ¹⁰ ■ ti CA) ung P ³ in X ² d, ■ Η ' U O > Hey ii 1 Hey Hey H Jl 3r 2 Hey Hey Jl H Cl 3 Xt Hey rl H J 4- At Ke ar St. Hey H H Cl 6th Hey Ke Hey - H J 7th lie ι'ΙΘ I K Br 8th iue I. J Ho Ko 9 lie j Ηε Cl Hey Ξγ

TABEL

III

Comparison of residual activity in sterilized soil (John Innes Potting Composition) and natural unsterilized soil (Kettering Loam) (A) from compounds of Tables I and (3) Compounds of Table II showing significant residual activity in sterilized soil

= ED

90

("J.I.P." - John Innes No, 1 potting composition and "KL" = Kettering Loam)

e effective dose Ib / acre

Jj.g.sd iu a 1 - (Bod en -), A kti y i t_ät-

u nsteril ized-e, earth). ·

sr; · .-] cd-pi

· Η! · Η sis «

■ ρ; J ^ GJ-H CQ>

0, i2t? \ ZL_,; I (

0.25 * θ! Ί

0.25 * 0 * 25

0 ^ _ "L0_ ^ 22r0_i5

LZZZ /

ro
t- ¹ OJ He j ■ He j E
I ί H cii '
cx> '-I
Cu "
»" - ■>
co
Jj :, ' O O
JXj
α H I?

link

j - C) J.
j Ί - ' O

ω j " α '

M et

Η ·

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From the above tables it can be seen that the test compounds 1-12 of Table I, which are representative of the thiazole derivatives according to the invention, are extremely effective as herbicides against the spectrum of tested weed species which are representative of the most diverse plant species play a role in the problems of weed control in agriculture, and that these compounds are effective as herbicides at very much lower application doses than the vast majority of the 63 test compounds which are representative of the chemically closest classes of thiazole derivatives, the in the British and French patents mentioned above, i ...- d chemically closely related compounds, ie the test compounds 13 - 15 * 19 > 20 and 22 - 75 · In addition, the latter compounds have proven to be herbicides at relatively low application doses effective against certain of the weed species tested am shown, but other species show much greater resistance making it necessary to use higher dosage levels if a wide range of weed species are to be kept under control. It can be seen that the minimum effective dose of a particular compound against all or a substantial majority of weed species is of particular "concern and qualification, as will be discussed below, since the individual weed species present in a Particular problem of weed control are encountered, vary from place to place and cannot be predicted with certainty and a broad spectrum of activity is therefore desirable for achieving flexibility in weed control at commercially acceptable application doses. Regarding the important qualification mentioned above, it should be noted that the selectivity in herbicidal activity between types of plant species may be of importance in certain weed control / planting situations Test compounds 10 and 11 require relatively high application rates to control the monocot Avena

109817/2227

-vs.

fatua and Alopecurus myosuroides when used in contact, doeh This is consequently not a real disadvantage, as this is a selective control of dicotyledon weed species Contact application or application after being absorbed in the absorbed Indicates monocot plantings «. They also show Test compounds 10 and 11 have a high level of herbicidal Re-.sidual activity, such as test compound 12, which is less effective in contact use, suggesting utility in the indicates control of weeds carried out before emergence by application to an open plantation »

A particularly valuable property of the new compounds of general formula II, which differs from the compounds specifically described in the patents mentioned, by the presence of a methyl or ethyl group on the urea nitrogen atom which is bonded to the thiazole ring, a chlorine -, bromine or iodine atoms in the 5-position of the thiazole ring and the absence of a substituent in the 4-position of the thiazole ring, is that the high degree of activity as residual herbicides, which is found when testing them in sterilized soil, as in Table I is not appreciably adversely affected, as found when the compounds are tested in unsterilized soil which approximates the conditions encountered in agricultural practice. Certain of the compounds of Table II specifically mentioned in or within the scope of the aforementioned British and French patents, ie test compounds 16, 17, 18 and 21, of which compound 16, ie N- (5-chloro- 2-thiazolyl) -N ^l -methylurea [or l- (5-chlorothiazol-2-yl) -3-methylurea] is on the whole the most effective of the known compounds, give results in the tests of contact activity and residual activity in sterilized Soils comparable to those of the compounds in Table I. These results are given in Tables I and II. However, the results of the tests of residual activity in unsterilized soil given in Table III show that test compounds 16 _} 17,

1098 17/2227

18 and 21 are less effective in non-sterilized soil and use significantly higher amounts for weed control than the compounds of the invention require.

It is known that the control of weeds in the greenhouse found application quantities almost always with a factor must be multiplied by 2 or sometimes by a factor of 4 for a comparable control under natural conditions in fields, and test compounds 16, 17, 18 and 21 are expected to produce application amounts "of at least 4.5 kg per hectare (4 lbs per acre) and probably 9 kg per hectare (8 lbs per acre) for an acceptable level Control of a number of weed species when used in fields as residual herbicides would require. This stands in stark contrast to the compounds according to the invention, which, as has been found, a satisfactory control of Weeds in fields result as residual herbicides at application rates of 1.12 to 2.4 kg per hectare (1-2 lbs per acre).

It follows that the test connections 16, 17, 18 and in practice, use at these higher, more uneconomical application levels for weed control when applied before emergence would have to be. (By the term "pre-rise application" is meant application on the ground in which the weed seeds or seedlings are present before the weeds emerge above the surface of the soil, for example on germinating weed seeds). When used in lower application amounts, the weed control would be on one application after emergence restricted to emerged weeds, in which case most of the plantings have emerged are. (Under the term "post-rise application" is the application to the air-exposed parts of the risen Weeds or the soil in which they grow). This would put a practical limitation on its use of considerable importance, since the range of crops that are against an application of these herbicides after

1 0 9 8 1 7/2 2 ■> 7

. ■■ .ν-: ■■■ 19

Emergence resistant is less than the range of crops that are resistant to pre-emergence application. It is also important to combat the weeds before they have settled to a competition with the crop during the critical growth stage of the latter, if they are risen 'and sticks _s to settle to avoid. For these reasons, the time of applying the herbicides that have only post-emergence activity to weed control is much more critical than that of achieving weed control by pre-emergence application. This is of particular practical importance, since the application, for example, · by spraying, can not be made under adverse weather conditions, and applying to the rising collapse requires successful use of herbicides the critical period of application and favorable weather conditions in many Cases cannot be predicted with certainty. In addition, weeds that germinate afterwards would not be attacked. This does not mean that herbicides that are effective when applied after emergence, have no practical utility because their use is satisfactory in many cases, but that the combination of effectiveness before and after the rise that, the inventive compounds finds ^ represents a great practical advantage.

Some of the compounds mentioned in the above British and French patents are stated to be they have a long persistence in the soil, but with these the application of at least the amount of active ingredient would be required, which has been found to be necessary «in order to obtain a herbicidal residual effects, and possibly still a larger amount, as the persistence of the herbicidal effect at least in part a function of the concentration of the herbicide is in the soil and by factors such as leaching. and biological decomposition of the herbicide.

It has been found that the compounds of general formula II

109817/2227

persistent herbicidal residual effects on the lower, more economical ones Application levels, at which they can be used, have the effect during the life of the Crop plants persist and continue to act against weed germination in the intervals after their application. This is from of great practical importance, since it often happens in agriculture that weeds continue abundantly during the critical period The growth time of the crop plants germinates when they are most easily adversely affected by competition from weeds.

A residual herbicide that has limited persistence is less useful and less economical than one that is has a greater persistence, since then a "repeated application is necessary to achieve satisfactory weed control.

For herbicidal purposes, the thiazole derivatives of the general formula II can be used as such or in the form of their agriculturally useful acid addition salts. The term "agriculturally useful acid addition salts" is to be understood as meaning salts which are usually acceptable in agricultural practice as suitable derivatives of herbicidally active bases, ie salts whose anions do not noticeably impair the herbicidal properties of the base and which do not have any properties which they do make unsuitable for use as herbicides. The thiazole derivatives of the general formula II are weak bases and the salts are consequently formed with strong acids. Examples of such salts are salts obtained from mineral acids, such as, for example, the hydrohalides, for example the hydrochlorides, hydrobromides and hydroiodides, and salts of strong organic acids, such as, for example, the p-toluenesulfonates. Acid addition salts useful in agriculture also include the hydrochlorides, hydrobromides and hydroiodides containing acetic acid, as described below. The agriculturally useful acid addition salts can be prepared as follows

109817/2 ^ 27

2OAO580

for the production of acid addition salts is described »

According to one feature of the present invention, at least one of the compounds of general formula II and their agriculturally useful acid addition salts for controlling the Weed (i.e., unwanted vegetation) growth is used. For this purpose they are usually in the form of herbicidal compositions (i.e. together with compatible Diluents or carriers suitable for use in herbicidal Compositions are suitable), for example as described below, used. ,

The compounds of general formula II and their agriculturally useful acid addition salts can be used to control the growth of dicotyledon weeds (ie broad-leaved weeds) and monocotyledon weeds (e.g. grasses) both by application after emergence and by application before emergence. The compounds of general formula II and their agriculturally acceptable acid addition salts may, for example to control the growth of weeds, for example Amaranthus retroflexus, Amsinckia intermedia, Anthemis arvensis _Λ Aphanes arvensis, Barbarea vulgaris, Brassica spp, "(eg, Sinapis arvensis), Gapsella bursal pastoris, Cerastium spp., (e.g. Cerastium holosteoides), Chenopodium spp. (e.g. Chenopodium album), Chrysanthemum segetum, Cirsium spp. (e.g. Cirsium arvense), Descurainea sophia, Emex australis, Equisetium arvense, Euphorbia esula, Galeopsis tetrahit, Galinsoga parviflora, Galium aparine _s Lamium purpureum, Matricaria spp., (e.g. Matricaria inodora and Matricaria spp. e.g. Polygonum aviculare, Polygonum convolvulus, Polygonum lapathifolium and Polygonum scabrum), Portulaea oleracea, Senecio vulgaris, Sonchus spp. (e.g. Sonchus oleraeeus), Spergula arvensis, Stellaria media, Tussilago spp. (e.g. Tussilago farfara) Urtica urens, Veronica spp. (e.g. Veronica agrestis, Veronica hederifolia and Veronica persica), Agropyron spp. (e.g. Agropyron repens), Alopecurus spp. (e.g. Alopecurus pratensis and alο-pecurus myosuroides), Avena fatua, Bracharia eruciformis, Bromus

10 9 8 17/2227

tectorum, Digitaria sanguinalis, Echinochloa spp. (e.g. Echinochloa crus-galll), Eleusine africana, Leptachloa filiformis, Pennisetum clandestinum, Poa spp. (e.g. Poa annua), Setaria spp. (e.g. Setaria vlridis), Cynodon dactylon and Sorghum halepense,

be used.

The amounts used of the compounds of the general formula II and their agriculturally useful acid addition salts vary with type of weed, type of soil, time of application and (if used to control growth of weeds in areas with growing crops) ^ the kind of crops. Taking these factors into account deliver application quantities between 0.28 and 2.25kg per hectare (1/4 to 2 lbs. Per acre) of active material gives good results. However, it should be noted that higher or lower application levels can be used depending on the particular problem the weed control in question.

The compounds of the general formula II and their agriculturally useful acid addition salts can be used to control the growth of weeds, for example of the abovementioned species, by application before or after emergence in an area with weed infestation, the one for cultivating maize, rice, wheat, barley , planting peas, beans, soybeans, peanuts, Baurnwoll- W, may be used potatoes and flax area used by the application before the rising of the crops. Application quantities of 0.56 to 2.24 kg per hectare (1/2 to 2 lbs per acre) of active substance are particularly suitable here and are well tolerated by the useful plants.

The persistent herbicidal effects of the compounds of the general formula II and its agriculturally useful acid addition salts when used before rising control of weeds during the critical growth period after emergence by suitable selection of the application time of useful plants.

1 η 9 B17 /? ? :> 7

The compounds of general formula II and their agriculturally useful acid addition salts can also be used before or after emergence to control the growth of weeds in existing orchards, in particular orchards with trees that grow in temperate zones, for example apple tree gardens, vineyards, plantations, for example, sugar cane, pineapple and banana plantations, plantations of shrubs (including areas growing for the cultivation of fruit-bearing bushes, especially in temperate zones shrubs, berries, for example blackcurrants ^J), and are used in forests. For this purpose, they are preferably applied directly (ie by direct spraying) to the weeds or the soil in which they are expected to occur, avoiding application to the tree-like plants. When used for such purposes where full herbicidal activity is often-desired, the active compounds are normally used in higher doses than those used in areas of growing crops such as mentioned above, in which the crops have not yet emerged or only recently opened and are not yet firmly established. For these purposes, application amounts of 1.12 to 4.5 kg per hectare (1.-4 lbs per acre) of active ingredient are generally suitable. However, higher or lower application levels can be used depending on the particular problem of weed control present. The duration of the herbicidal effects of the compounds of general formula II and their agriculturally useful acid addition salts when used before emergence enables weed growth to be controlled for useful periods of time, depending on the amount used, for example 1 > to \ months, but not for excessively long periods of time could lead to difficulties if it is desired to plant the treated area with useful plants which would be adversely affected by the herbicidal action if it were still present.

The compounds of general formula II and their agricultural usable acid addition salts can also by

1098 17/2227

Use before or after emergence to control weeds, for example of the above-mentioned species, in particular of grass weeds, in existing cereal crops, for example in hardy wheat and hardy barley, and in transplanted crops, such as leguminous rice, and for Prevent weeds from recurring due to their permanent herbicidal effects when applied before emergence be used. For this purpose, application amounts of 0.56 to 2.24 kg per hectare (1/2 to 2 lbs per acre) of active ingredient good, with these application quantities' are well tolerated by the useful plants.

The compounds of the general formula II and their agriculturally useful acid addition salts can also be used before or after emergence to control the growth of weeds, such as the aforementioned species, in particular the perennial weeds, such as, for example, Cirsium spp., Sonchus spp., Tussilago spp. and Agropyron spp., used in non-agricultural areas such as airfields, industrial sites, railroad lines and road or path edging and edges, and in drachand or uncultivated areas, where by their persistent herbicidal effects when applied Prevent re-infestation before opening. When used for these purposes where full herbicidal activity is often desired, the active compounds will normally be used in higher dosages than those in areas of growing crops. For these purposes, application amounts of 2.25 to 4.5 kg per hectare (2-4 lbs per acre.) Of active ingredient are generally suitable. However, higher or lower application levels can be used depending on the particular problem of weed control present.

The compounds of general formula II and their agriculturally useful acid addition salts can also be used as defoliation agents and desicaants in plantations, for example

Cotton and potato plantings. To this

10981 7/2227

Use amounts of -1.12 are generally suitable for purposes up to 2.2-5 kg per hectare (1-2 lbs per acre) of active ingredient »

According to features of the present invention, the compounds of the general formula II prepared by the following methods s

(a) Bromination, chlorination carried out by customary methods or iodination of compounds of the general formula

in which Fk, R ₁ - and Rg have the meanings given above, using suitable brominating ₅ chlorinating or iodinating agents (ζ.Β »chlorine, sulfuryl chloride, bromine, hydrobromic and hydrobromic acid, iodine monochloride or - an alkali metal iodide, z "B _o potassium iodide, and a Alkalijodat such as potassium iodate) in the presence of water or an inert organic solvent. * such as a halogenated aliphatic hydrocarbon, such as chloroform, 1,2-dichloroethane, or sym-tetrachloroethane, a lower aliphatic acid, for example acetic acid, or an aqueous lower alkanol Z ₀ B ₀ aqueous ethanol, if necessary, for example in the case of iodination with an alkali iodide and alkali iodate, in the presence of an inorganic acid such as sulfuric acid.

[In the following methods (b) to (k), Z represents a bromine, Chlorine, iodine or hydrogen atom. It can be seen that, if Z denotes a bromine, chlorine or iodine atom, the products obtained are compounds of the general formula II. If Z represents a hydrogen atom, the products obtained are Compounds of general formula IV, which are used as starting materials can be used in the method described in (a) above

109817/22 27

(b) If Rp. represents a hydrogen atom and Rg a methyl group means conversion of compounds of the general formula

NHR,

in which Rj, and Z have the meanings given above, with Methyl isocyanate in an inert organic solvent, for example acetone or acetonitrile, preferably at elevated levels Temperature.

The compounds of the general formula V for which Z represents a hydrogen atom can be made known per se by application Methods are produced, for example by

(i) Reduction of compounds of the general formula

VI

in which R ₁₁ denotes a hydrogen atom or a methyl group, with lithium aluminum hydride in an inert organic solvent, such as, for example, diethyl ether.

The compound of the general formula VI, for which R ^ ₁ denotes a hydrogen atom, can be prepared, for example, by reacting 2-aminothiazole with formic acid at elevated temperatures. The compound of the general formula VI, for which R _{11 is} a methyl group, can be obtained by reacting 2-aminothiazole with acetic anhydride or acetyl chloride in the presence of an acid-binding agent such as pyridine, which is also known as

109817/2227

Solvent can be used for the reaction, or triethylamine, and, if desired, in the presence of an inert organic solvent, such as, for example, a ketone, e.g. acetone, are produced,

(ii) hydrolysis of compounds of the general formula

VII

in which R ^ has the meaning given above. ' The hydrolysis is preferably carried out by treatment with a dilute mineral acid such as dilute hydrochloric acid, if desired carried out at elevated temperature.

Compounds of the general formula VII can be prepared by reacting 2-aoetamldothiazole with compounds of the general Formula RhT, in which R ^ has the meaning given above and T is an acid residue of a reactive ester, for example is a bromine or chlorine atom or a sulfuric acid or sulfonic acid ester residue, in the presence a basic condensing agent such as an alkali hydride such as sodium hydride in an inert organic Solvent, for example dimethylformamide, can be produced.

(iii) Reaction of l, l-diethoxy-2-chloroethane or l, l-dichloro-2-ethoxyethane with compounds of the general formula H ₂ NCSNHR ^, in which R ₁ ^ has the meaning given above, in aqueous solution in the presence a small proportion of a mineral acid, such as hydrochloric acid, preferably at an elevated temperature, for example at 95-100 ^° C.

10 9 8 17/2227

The compounds of the general formula V, for which Z represents a bromine, chlorine or iodine atom, can be carried out by bromination, chlorination or iodination of the corresponding compounds of the general formula V, for which Z represents a hydrogen atom, carried out by customary methods, for example according to the ^ method described above under (a) according to the above (i) and (ii) methods described, the bromine present in the 5-position, chlorine or Jodaton, by known methods, for example according to the above (a) described Process is introduced in any suitable stage of the reaction sequence, for example by bromination, chlorination P or iodination of the compounds of the general formula VII before the hydrolysis , or by preparing compounds of the general formula VII from 5-bromine, 5- chlorine or 5- Iodine-2-aminothiazoles and 5-bromo-, 5-chloro- or 5-iodo-2-acetamidothiazoles are produced.

The compounds of the general formula V for which Z represents a bromine or chlorine atom can be prepared by reacting l, l-diethoxy-2,2-dibromoethane or l, l-diethoxy-2,2-dichloroethane with compounds of the general formula H ₂ NCSNHRh, in which Rj, has the meaning given above, are prepared under the reaction conditions described under (iii) above.

(c) Implementation of compounds of the general formula

VIII

Z ^> N-CO ₂ R ₁

in which Rj, and Z have the meanings given above and RjP is a lower alkyl group of 1-6 carbon atoms or preferably an aryl group, especially a phenyl group, represents, with an amine of the general formula

HNR ₅ R ₆ IX

1 0 9 8 1 7/2 2 Ί 7

in which Rt and Rg have the meanings given above, preferably in the presence of an inert organic solvent, such as, for example, a lower alkanol, e.g. ethanol, or preferably an aromatic hydrocarbon such as benzene. The. Reaction can take place at room temperature under atmospheric pressure or if desired under pressure or if desired under Pressure and at elevated temperature can be carried out.

The compounds of the general formula VIII can by reaction of the compounds of the general formula V with compounds of the general formula

in which R ^ _{2 has} the meaning given above and X represents a chlorine or bromine atom, in the presence of an acid-binding agent such as pyridine, and if desired in the presence of an inert organic solvent such as a ketone, e.g. acetone.

The compounds of general formula VIII for which Z is Bromine, chlorine or iodine atom can also be carried out by bromination, chlorination or iodination carried out by customary methods of compounds of the general formula VIII for which Z represents a hydrogen atom, for example according to the above process described under (a).

(d) Implementation of compounds of the general formula

XI

in which R ^, X- and Z have the meanings given above, with an amine of the general formula IX in which R ₁ - and Rg have the meanings given above, preferably in one

1098 17/2227

inert organic solvent such as an aromatic one Hydrocarbon, e.g. toluene, a halogenated aliphatic hydrocarbon, e.g. chloroform, a ketone, e.g., acetone, or a lower alkanol, e.g., ethanol, in the presence of a suitable acid binding agent such as Sodium carbonate, triethylamine or an excess of the amine reagent.

The compounds of general formula XI can by customary methods, for example by reacting the compounds of general formula V with phosgene, preferably in the presence of an inert organic solvent, such as, for example an ether, e.g. diethyl ether, or an aromatic hydrocarbon, e.g., toluene, in the presence of a suitable acid binding agent, e.g., triethylamine.

The compounds of general formula XI for which Z is Bromine, chlorine or iodine atom can also be carried out by bromination, chlorination or iodination carried out by customary methods of compounds of the general formula XI, for which Z denotes a hydrogen atom, for example according to the above under (a) described method.

(e) If R _{r represents} a methyl group, reaction of compounds of the general formula V with compounds of the general formula

CH

"Z,

X, CON XII

in which X ^, and R ^ have the meanings given above, in Presence of an acid-binding agent, such as pyridine, which can also serve as a solvent for the reaction, or triethylamine, if desired in the presence of an inert one organic solvent such as a ketone, e.g. acetone.

109 8 17/2227

(f) Reaction of compounds of the general formula V with compounds of the general formula

^R 5

NCON XIII

in the R - and Rg are as defined above, at elevated temperature, for example at I50 - 25O ⁰ C, preferably in the presence of an inert organic solvent, such as an inert hydrocarbon solvent with a boiling point of I50 - 250 ⁰ C.

(g) Treatment of compounds of the general formula

xrv

in which the various symbols have the meanings given above have, according to conventional methods for transferring a thioureldorestes into a ureido residue, for example by treatment with a lead or mercury compound, such as Lead nitrate or mercury (II) oxide.

The compounds of the general formula XIV can by processes which are analogous to processes (a) to (f), where the present or formed during the reaction sequence Ureido residue is replaced by a thioureido residue.

(h) If Rf- represents a methyl group, reaction of compounds the general formula

109817/2227

7040580

NR ₁ ,

XV NCONIICH,

in which R ^ and Z have the meanings given above, with Compounds of the general formula

RgT XVI

in which Rg and T have the meanings given above, preferably in the presence of an inert organic solvent such as dimethylformamide, in the presence of a suitable P Net basic condensing agent such as an alkali hydride, e.g., sodium hydride.

(i) If Rc represents a methyl group, reaction of compounds the general formula

^N R

XVII

NCONHR, -

"NK ⁶

in the Z, R ₁ . and Rg have the meanings given above, with compounds of the general formula

CIUT XVIII

in which T has the meaning given above, under the conditions described above under (h).

(j) If Rj ,, Rj- and Rg each represent a methyl group, Implementation of compounds of the general formula

• NHCONHRc- XIX 5

in which R ^ and Z have the meanings given above, with

109 8 17 / 2.2 2 7

Compounds of the general formula XVIII under the conditions described above under (h).

(k) If R ^ and R ₁ - each denote a methyl group, reaction of compounds of the general formula

XX

NHCONHR ^

in which Rg and Z have the meanings given above, with Compounds of the formula XVIII under the conditions given above under (h).

The compounds of general formula XV and XVII can also by the methods (a) to (g) given above. The compounds of the general formula XIX and XX can also by the methods (a) to (g) given above, but using thiazole derivatives for which R ^ is a hydrogen atom means to be produced.

It should be noted that in the aforementioned methods (c) to (i), the meanings of Rh, Re and Rg must be chosen so that they give the defined meanings of these symbols in the products of general formula II.

The acid addition salts of the compounds of the general formula II can by treating the bases with a strong acid, such as a mineral acid, e.g. a hydrohalic acid, e.g. hydrochloric acid or hydrobromic acid, or a strong organic acid, e.g. p-toluenesulphonic acid, Benzenesulfonic acid or methanesulfonic acid, in a suitable one Solution agent, such as a halogenated one , Hydrocarbon, e.g. chloroform, a ketone, e.g. acetone, or a lower alkarn: .- ..?, B. Ethanol, manufactured by £ - »n. The salts can, if necessary, by crystallization Concentration of the reaction medium, can be isolated.

1098 17/2227

The acid addition salts of the compounds of the formula II can be prepared directly from the reaction medium in which they are prepared can be isolated by treatment with a strong acid without isolating the base.

If the reaction was bromination, chlorination, or iodination, the one set free during the reaction forms Hydrogen halide an acid addition salt with the compound of formula II, which can be isolated as such. If the bromination, chlorination or iodination is carried out in acetic acid the isolated salt may contain acetic acid. However, acetic acid itself is not a sufficiently strong acid to directly form salts of the compounds of formula II.

The following examples serve to further explain the preparation of the new thiazole derivatives according to the invention. The specified niesh sieve sizes are British sieve sizes.

example 1

1- (5-bromothiazol-2-yl ) -l, 3- dimethyl urea

A solution of 2.35 ml of bromine in 5 ml of dry chloroform was added over the course of 30 minutes to an ice-cold solution of 8 g of 3-dimethyl-1- (thiazol-2-yl) urea in 45 ml of dry chloroform with stirring. When the addition was complete, the ice bath was removed and stirring continued for a further 30 minutes. The insoluble material was separated, washed with chloroform and dried in vacuo over silica gel. This gave 1- (5-bromothiazol-2-yl) -l, 3-dimethylurea hydrobromide with a melting point of 212-213 ° C. (decomp.). This material was then boiled in 350 ml of water and 10 ml of 2N sulfuric acid. The hot solution was decanted from the insoluble material and allowed to cool. There were thus 3.7 g of l- (5-Bromo-thiazol-2-yl) -l, 3-dimethylharn5toff in the form of a white solid substance of F = 122 - 124 ⁰ C obtained.

The 1,3-dimethyl-l- (thiazol-2-yI) urea used as starting material was made as follows:

1098 17/2227 BADOHJßINAL

A solution of 11.4 g of 2-methylaminothiazole (manufactured according to Wilson and Woodger, J. Chera. Soc, 1955 * 2946) in 50 ml of anhydrous Acetone was mixed with a solution of 5 * 7 g of methyl isocyanate mixed in 20 ml of anhydrous acetone. After stopping the weak exothermic reaction, the mixture was refluxed for one hour. The acetone was then allowed to evaporate, and the remaining Pest substance was crystallized from 180 ml of water. It was 1,3-Dlmethyl-l ~ (thiazol-2-yl) urea in the form of a obtained white powdery substance from P = 100 to 10l ° C.

Example 2 1- (5- bromothiazol-2-yl) ~ 1,3-dimethyl urea

A solution of 0.57 g of methyl isoeyanate in 1 ml of anhydrous acetone was added to a solution of 1.9 g of crude 5-bromo-2-methylaminothiazole in 10 ml of anhydrous acetone. After the mildly exothermic reaction had ceased, the mixture was refluxed on a steam bath for 2 1/2 hours. The acetone was allowed to evaporate, and the residual sticky Pestsubstanz was treated with petroleum ether - and then triturated with 25 ml of petroleum ether (boiling range ι 4θ 60 ° C) (range: .. 80-100 ⁰ C) cooked. The hot solution was decanted off from the insoluble material and cooled, whereby 1.2 g of 1- (5-bromothiazol-2-yl) -1,; 5-dimethylurea in the form of a white pest substance with a P = 121-122 ° C were obtained. The melting point remained unchanged when mixed with material prepared according to Example 1.

The crude 5-BFom-2-methylamino ~ used as starting material thiazole was made as follows:

16 g of bromine were introduced within 50 minutes with the aid of a stream of air into a mixture of 11.4 g of 2-methylaminothiazole, 125 ml of concentrated (48%) hydrobromic acid and 40 ml of water, which was stirred and, if necessary, by external cooling with water was kept at IJ - 16 ° C. The resulting solution was then refluxed for 5 minutes and ^{cooled to 0} ° C., this temperature being maintained overnight

^! " ^V ^" ^W ^ 109817/2227

became. The pH of the solution was then adjusted by adding first solid sodium carbonate and then solid sodium bicarbonate under External cooling (ice water) brought to 7 with stirring. The precipitate was separated off, washed with ice water and in vacuo dried over silica gel. This gave 6.2 g of crude 5-bromo-2-methylaminothiazole obtain.

Example 3 1- (5-chlorothiazol-2-yl) -l, 3-dimethyl urea

A solution of 9> 9 tnl sulfuryl chloride in 10 ml anhydrous Chloroform became a solution of in 30 minutes 18.4 g of 1,3-dimethyl-l- (thiazol-2-yl) urea (prepared as described in Example 1) in 100 ml of anhydrous chloroform are added, v / obei the solution is stirred and carried out as required External cooling with V / ater was kept at 20-25 ° C. After the addition was complete, the solution was left for a further 1 1/2 hours at room temperature touched. The chloroform was then allowed to evaporate and the remaining material was extracted with v / ater, The pH of the aqueous extracts was raised by adding solid sodium bicarbonate with stirring and external cooling (ice water) 7 brought. The mixture was then extracted with chloroform and that obtained by evaporating the chloroform extracts to dryness Solid substance crystallized from hexane. It became l '- (5-chloro- "thiazol-2-yl) -l, 3-dimethylurea in the form of a white pest substance obtained from P = 115 - 117 C.

Example 4 1- (5-bromothiazol-2-yl) -l-ethyl-3-methy! Urea

A solution of 1.17 ml of bromine in 5 ml of anhydrous chloroform was converted into an ice-cooled solution of 3.7 g of l-ethyl-3-methyl-l- (thiazol-2-yl) urea in 20 minutes within 15 minutes ml of anhydrous chloroform were added with stirring. After stirring for a further 1 hour at room temperature, the solution was shaken with excess aqueous sodium bicarbonate solution and then with water. The chloroform was removed by evaporation

^: 1098 17/2227

removed under reduced pressure, and the remaining dark colored, weakly oily solid was crystallized from 30 ml of benzene, with 0.95 g of 1-5- (bromothiazol-2-yl) -l-ethy1-3-methy1-urea from F =. 127 to 128 ⁰ C were obtained.

The 1-ethyl-3-methyl-1- (thiazol-2-yl) urea used as starting material was made as follows;

8.9 g of methyl isocyanate were added to a solution of 20 g of 2-ethylaminothiazole (prepared according to Kay and Parris, J. Org. Chem., 1952, 17., 737) in 130 ml of anhydrous acetone was added. To The mildly exothermic reaction ceased - the solution was up refluxed on a steam bath for 3 hours. The acetone was then removed by distillation under reduced pressure, and the remaining solid was crystallized from 65 ml of benzene. This gave 11.9 g of 1-ethy 1-3-methy 1-1- (thiazol-2-yl) urea obtained in the form of a not completely white solid substance from F = 101 - 1O2 ° C.

Example 5 '

1- (5-bromothiazol-2-yl) -1,3,3-trimethylurea

A solution of 1.6 g of bromine in 10 ml of anhydrous chloroform was added dropwise within 20 minutes to a solution of 1.85 g of l- (thiazol-2-yl) -1,3,3-trimethylurea in 10 ml of dry chloroform, which was stirred and cooled in an ice bath, was added at a rate such that the temperature of the mixture did not rise above 10 ° C. After the addition was complete, the mixture was stirred at room temperature for 2 hours. The chloroform was then removed in vacuo on a rotary evaporator at 10-20 mm Hg, and the remaining glassy material was triturated with diethyl ether, giving 3.2 g of crude 1- (5-bromothiazol-2-yl) -l, 3 » of 3-trimethylurea hydrobromide obtained in the form of a cream-colored powder "This powder was hicarbonatlösung with excess aqueous saturated sodium collected _f triturated, washed with water and dried in vacuo over silica gel getroaknet. There were so 2.1 g of 1- (5-bromothiazol-2-yI) -I, 3,3-trimethy1-

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Urea obtained in the form of a white pest substance from P = 67 ⁰ C. The melting point was raised to 69 ° C. by recrystallization from hexane.

The l- (thiazol-2-yl) -l, 3> 3-trimethylurea used as starting material was made as follows:

A mixture of 17 g of phenyl-N-methyl-N-thiazol-2-yl-carbamate and 1 ¹ IO ml of 30 $ strength (wt./wt.) Solution of dimethylamine in ethanol was kept for 36 hours at room temperature. The ethanol was then removed in vacuo on a rotary evaporator at 10-20 μm Hg and the remaining oil was steam distilled until all traces of phenol were removed. The water was then removed from the aqueous solution obtained by evaporation on a rotary evaporator at 10-20 mm Hg and the remaining brown oil was dissolved in chloroform. The chloroform solution was dried over magnesium sulfate and distilled. 7.9 g of l- (thiazol-2-yl) -l, 3,3-trimethylurea were obtained in the form of a colorless oil, which was collected at 120-122 ° C. at 0.25 mm Hg.

The phenyl-N-methyl-N-thiazole used as starting material - ^ - yl carbamate was made as follows:

18 g of phenyl chloroformate was added dropwise to a solution of 11.4 g of 2-methylaminothiazole (Wilson and Woodger, J. Chem. Soc, 1955, 2944) in 60 ml of anhydrous pyridine, the solution being kept stirring and so cooled in an ice bath was that the temperature did not exceed 10 C. After the addition was complete, the mixture was kept at room temperature for 65 hours. Then it was diluted with a mixture of ice and water, and the precipitated crude phenyl-N-methyl-N-thiazol-2-yl-earbamate was collected, washed successively with v / water, dilute aqueous hydrochloric acid and water and in vacuo dried over silica gel. This gave 21.6 g of a white solid substance. Which melted point of this product was 83-86 ⁰ C and increased by recrystallization from hexane to 89 ⁰ C.

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Example 6 1- (5-eromthiazol-2-yl) -l, 3-dimethyl urea

290 g of methyl isocyanate were added dropwise over 90 minutes to a mixture of 570 g of 2-methylaminothiazole, 1200 ml of acetonitrile and 5 ml of triethylamine with stirring. The reaction temperature rose spontaneously from 19 ° C to 51 ⁰ C. The reaction mixture was then heated and 3 hours at 60 - 65 ⁰ C stirred. The solvent was then distilled off using a water jet pump, the distillation temperature being kept below 45.degree. The residue solidified.

The melting point of the residue was 98-100 ⁰ C. The residue was dissolved in 4 1 of glacial acetic acid and the solution stirred in an ice bath to lower the temperature to 12 ° C. 800 g of bromine in 500 ml of glacial acetic acid were then added dropwise to the solution over 90 minutes. The reaction temperature rose spontaneously to 27 ° C. The reaction mixture was then stirred without heating for 15 hours and filtered. The residue was washed with 5 l of glacial acetic acid and sucked dry on the filter. The residue was then stirred with 4 l of water, while 2 kg of sodium bicarbonate were added in portions over the course of 2 1/2 hours. The reaction mixture was then stirred for 4 hours and filtered, and the residue was washed with 6 l of water and dried in a stream of warm air. There were so I070 g l- (5-Bromo-thiazol-2-yl) -l _{J-dimethylurea} 3 in the form of a white solid substance of F - 118 - 12O ° C obtained.

Example 7 1- (5-Bromothiazol-2-yl) -l, 3-dimethyl urea

A solution of 6.88 ml of bromine in 20 ml of glacial acetic acid was added dropwise to a solution of 20 gl, j5-dimethyl4- (thiazol-2-yl) urea (prepared as in Example 1) in 80 ml of glacial acetic acid with stirring, the reaction temperature was kept at 20 - JO C. After the addition had ended, the reaction mixture was stirred at room temperature for 14 hours. The precipitate was then filtered off, washed with diethyl ether and in vacuo at room temperature

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temperature dried. Aqueous sodium bicarbonate solution was added to the pest substance and then solid sodium bicarbonate added, until no further reaction could be observed. The solid was then filtered off, washed with water and poured over Phosphorus pentoxide dried in vacuo, 25.26 g of 1- (5-bromothiazol-2-yl) -l, 5-dimethylurea in the form of a white solid substance with an temperature of 120 - 121 ° C.

Alternative working methods to the preparation of the above starting material used 1,5-dimethyl 1-1- (thiazolyl) -ureas were used were the following:

(a) 300 ml of methyl isocyanate were added within 50 minutes to a mechanically stirred solution of 570 g of 2-methylaminothiazole in 1.5 l of acetonitrile, which was kept below 50 ° C. by cooling with cold water. The reaction mixture was then stirred at 60 ° C. (bath temperature) for 4 hours. As much acetonitrile as possible was then removed by distillation under reduced pressure (20 mm Hg) at 60 ° C (bath temperature). The brown oil was allowed to solidify, the product obtained was comminuted and dried in a vacuum drying cabinet at 55 ° C./20 mm Hg for 4 hours. The product was then coarsely powdered by sieving through a 50 mesh screen. The powder was then triturated with 700 ml of water and the insoluble material was collected, washed with 100 ml of water and dried, first in air and finally in vacuo over silica gel. There were 619 gl so, 3-dimethyl-l- (thiazol-2-yl) -urea in the form of a shiny white powder F = 100 - 102 ⁰ C obtained.

(b) A mixture of 5 g of phenyl-N-methyl-N-thiazol-2-yl-carbamate (prepared as described in Example 5) and J> 0 ml of a 50 # (weight per weight) ethanolic monomethylamine solution was at room temperature Left for 6 days. The ethanol was then evaporated by evaporation on a rotary evaporator at a bath temperature of 55 ° C and the remaining oil was subjected to steam distillation until it was free of phenol. The aqueous solution obtained was on a rotary evaporator to

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SA

Evaporated to dryness and the remaining solid was treated with decolorizing charcoal and recrystallized from water. There were obtained 101.5 ⁰ C 0.4 g of 1,3-Dimethy1-1- (thiazol-2-yl) -urea from P =.

(c) 5.8 ml of a 21.4% (weight per volume) aqueous monomethylamine solution was added dropwise with stirring to a solution of 3.4 g of N-methyl-N- (thiazol-2-yl) carbamoyl chloride in 10 ml Acetone added * Stirring was continued for 15 minutes and the acetone was then evaporated under reduced pressure. The residue was filtered off, washed with water and recrystallized from water. There were thus 2.9 gl, j5-dimethyl-l- (thiazol-2-yl) urea obtained in the form of an off-white solid of F = ⁰ G 99 -'105.

The N-methyl-N- (thiazol-2-yl) carbamoyl chloride used as starting material in the above preparation was prepared as follows:

A solution of 56 g of 2-Methylarninothiazol and 49.4 g of triethylamine in 300 ml of anhydrous Diäthylather was within 1 hour to 250 ml to a stirred saturated solution of phosgene in anhydrous Diäthylather at 0 ⁰ C was added. The reaction mixture was then stirred at 15 ° C. for 18 hours and then refluxed for 24 hours. 500 ml of anhydrous diethyl ether was then added and the reaction mixture was distilled, collecting about 500 ml of distillate. 1 liter of anhydrous diethyl ether was added to the residue. The resulting suspension was filtered and the residue washed with 1 liter of anhydrous diethyl ether. The filtrate and washings were combined and the diethyl ether was evaporated to give 4-6.1 g of N-methyl-N- (thiazol-2-yl) carbamoyl chloride, melting at 51 ° -52 ° C.

Example 8

2.9 ml of a 23.4 $ (weight per volume) aqueous monomethyl

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amine solution was added dropwise with stirring to a solution of 2.6 g N- (5-bromothiazol-2-yl) -N-methylcarbamoyl bromide (the one little Amount of the corresponding carbamoyl chloride contained) in 13 ml of acetone admitted. A weakly exothermic reaction took place. Stirring was continued for 15 minutes and the acetone was released then removed under reduced pressure. The precipitate was filtered off, washed well with water, dried and removed from water recrystallized. 1.86 g of 1- (5-bromothiazol-2-yl) -l, 3-dimethylurea were obtained obtained from F = 122 - 123 ° C.

The "N- (5-bromothiazol-2-yl) -N-methylcarbamoyl bromide used as the starting material in the above preparation became as follows manufactured:

16.0 g of bromine were added within 30 minutes to a solution of 17.7 g of N-methyl-N- (thiazol-2-yl) carbamoyl chloride (prepared as described in Example 7) in 350 ml of 1,2-dichloroethane Stirring added. The pale yellow reaction mixture was then refluxed with stirring for 3 hours during which time there was copious evolution of hydrogen chloride and hydrogen bromide. The solvent was then removed under reduced pressure. This gave 2 ^, 9 g of N- (5-bromothiazol-2-yl) -N-methylcarbamoyl bromide in the form of a pale yellow solid substance of F = 85.5 ~ 88, O ⁰ C k with a content of some N- (5 -Bromothiazol-2-yl) -N-methylcarbamoyl chloride.

Example 9 1- (5-Bromothiazol-2-yl) -l, 3-dimethylha rns toff-hydrobromide acetate

A solution of 3.4 ml of bromine in 10 ml of glacial acetic acid was added dropwise to a solution of 10 g of 1,3-dimethy1-1- (thiazol-2-yl) urea (prepared as described in Example 1) added in 20 ml of glacial acetic acid with stirring, the temperature being kept at 0-5 ° C became. The reaction mixture was left for 1 hour at room temperature stirred and the precipitate was filtered off with diethyl ether washed and dried in vacuo. This gave 21 g of 1- (5-bromothiazol-2-yl) -l, 3-dimethylurea hydrobromide acetate obtained from F = 214 ° C.

1.0.9 _T 8r1 7/222 7

Example 10 '9 *

1- (5 "bromothiazol-2-yl) -1, 3-dimethylurea hydrobromide

5.72 ml of a 50% (weight per weight) aqueous hydrogen bromide solution was added dropwise to a solution of 13.5 g of 1- (5-bromothiazol-2-yl) -l, 3-dimethyl urea (prepared as in Example 1 described) added in 50 ml of chloroform with stirring. The precipitate was filtered off and dried in vacuo. There were thus 15.24 g of l- (5-Bromo-thiazol-2-yl) -l, 3-dimethyl-urea hydrobromide from F = 213 - 214 receive ⁰ C (dec.).

Example 11 ■

1- (5-chlorothiazol-2-yl) -l, 3-dimethyl urea f

5 ml

A solution of 5 * 7 ml of methyl isocyanate in / acetonitrile was added within 5 minutes at 20 - 30 ⁰ C are added to to a stirred, cooled with water suspension of 12 g of 5-chloro-2-methylaminothiazole in βθ ml acetonitrile. At the end of the addition, a cloudy solution had formed, which was then ^{heated for 1 hour at 45-50 °} C. with stirring. The solution was then concentrated at 30 ° C. under reduced pressure, a brown solid substance being obtained which was then dissolved in 1 l of hot water / water. A sufficient quantity of sodium metabisulfite added to the solution to decolorize, which was then cooled to -1O ⁰ C. The solution was then allowed to warm to room temperature. The precipitated, slightly contaminated 1- (5-chlorothiazol-2-yl) 1,3-dimethyl urea (4.8 g) was filtered off, treated with decolorizing charcoal and recrystallized from 450 md η-hexane. There were thus 3.2 g of l- (5-Chlorthia2ol-2-yl) -l, 3-dimethyl-urea as a white crystalline solid of F = 118 - 118.5 ⁰ C obtained.

The S-chloro-ß-methylamLnothiazole used as starting material was made as follows:

A solution of 29.4 g of sulfuryl chloride in 100 ml of anhydrous chloroform'wurde within 40 minutes at 10-20 ⁰ C to an ice-cooled solution of 50 g of N-methyl-2-acetamido-thiazole

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added in 300 ml of anhydrous chloroform with stirring. After complete addition, the ice bath was removed and stirring continued for a further hour. The insoluble material was collected, washed on the filter with chloroform and dried to give 61.5 g of N-methyl - ^ - acetarnido - ^ - chlorothiazole hydrochloride a white Pestsubstanz from F = 145 in the form - were obtained 150 ⁰ C, the triturated with sodium bicarbonate and ice, washed with water and dried. Was obtained as 32.5 g of N-methyl-2-acetamido-5-chlorothiazole from F = 73 ⁰ C. This product was mixed with 3 ml of 10 ^ 0 $ strength (weight per volume) aqueous hydrochloric acid and heated under reflux for 20 minutes . Then decolourisation "was bung charcoal added and the mixture heated an additional 10 minutes at reflux then the mixture was filtered, cooled and with continued cooling with 80 g solid sodium carbonate in 9 -. Neutralized 10 ⁰ C up to pH 6 The insoluble material was collected. , washed once with water and in a desiccator at ⁰ C dried. There was thus 11.1 g of 5-chloro-2-methyl-aminothiazol in the form of a white solid substance (when stored at 0 ⁰ C pink becoming) from F = 75 - 77 ° C.

The N-methyl-2-acetamidothiazole used as the starting material in the above preparation can be obtained by the following method P can be produced:

57 grams of warm molten 2-methylaminothiazole was slowly added in portions to 59 ml of acetic anhydride with stirring. The first addition was 5-10 ml, after which the temperature rose slowly to 58 ^° C. The remainder of the addition took place within 10 minutes at 75-80 ° C. After the addition was complete, the mixture was heated on a steam bath for 2 hours and poured into 1 liter of ice water. The insoluble material was collected, washed with ice water and dried, whereby 42.3 [beta] N-methyl-2-acetamidothlazole was obtained as a white solid of F-89C.

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Example, 12 l- (5-chlorothiazol-2-yl) -l, 3-dimethyl urea

A solution of 1β2 ml of freshly distilled sulfuryl chloride in 400 ml of dry sym.-tetrachloroethane was added dropwise within 8 hours to a filtered, mechanically stirred solution of 542 g of 1,3-dimethy1-1- (thiazol-2-yl) urea ( prepared as described in Example 1 or 7) in 1 1 of sym.-tetrachloroethane was added, which was kept at 0-5 ° C by cooling in a dry ice / acetone bath. The reaction mixture was kept for 64 hours at O ⁰ C and then 18 hours at 6o ° C (bath temperature). The reaction mixture was then cooled and filtered. The white residue was washed on the filter three times with 100 ml of anhydrous sym.-tetrachloroethane each time and then six times with 250 ml of water-free diethyl ether each time. After drying in vacuo over silica gel, the solid substance (174 g) was stirred with 200 ml of water and the pH of the aqueous phase was brought to 2 by the gradual addition of aqueous 2N sodium carbonate solution (67O ml). The insoluble white solid was collected, washed with 120 ml of water and dried in vacuo over silica gel. There were 124 gl ~ so (5-Chloro-thiazol-2-yl) -l, 3-dimethyl-urea as a white solid from the obtained F = 118 120 ⁰ C. The sym. Tetrachloroethane mother liquors and washing liquids were combined and extracted twice with 500 ml of 6N hydrochloric acid each time. The combined acidic extracts were shaken with activated charcoal, filtered and mechanically stirred while 500 g of sodium bicarbonate were added until the The pH was 2. The precipitated crude 1- (5-chlorothiazol-2-yl) -l, 3-dimethylurea (129 g), melting point 114-119 ° C., was collected, washed with water and dried.

Another extraction of the sym.-tetrachloroethane mother liquors with 6N hydrochloric acid (two times 50O ml) and the treatment of the acidic extracts, as described above, 10 g of crude 1- (5-chlorothiazol-2-yl) -l, 3-dimethyl urea were obtained from F = 117-12O ° C.

10 9 8 17/2227.

All of the crude 1- (5-chlorothiazol-2-yl) -1, jS-dimethylurea (139 g) was dissolved in 2.1 l of 2N hydrochloric acid. The solution was then treated with activated charcoal and filtered, and the pH of the filtrate was brought to 2 by the gradual addition of sodium carbonate (about 300 g) with mechanical stirring. The precipitate was separated, washed with water and dried to give 124 g of l- (5-Chloro-thiazol-2-yl) -l, 3-dirnethylharnstoff of F = 118-120 ⁰ C were obtained.

Example I3

1- (5-chlorothiazol-g-yl) -l, 5-dimethyl urea

A solution of 1.15 g of monomethylamine and 4 g of phenyl ~ N- (5-chlorothiazol-2-yl) -N-methylcarbamate in 60 ml of anhydrous benzene was left in a sealed flask at room temperature for 2 days calmly. The reaction mixture was then subjected to steam distillation until there was no more phenol in the distillate and the remaining aqueous solution was concentrated in vacuo to give 1.9 g of a white solid which was then dissolved in 100 ml of 2N hydrochloric acid. The pH of the solution was brought to 3 by adding solid sodium bicarbonate. The precipitated solid was filtered off and dried. 1.42 g of 1- (5-chlorothiazol-2-yl) -l, 3-dimethyl urea were obtained from F = 117 - 119 ° C.

The phenyl N- (5-chlorothiazol-2-yl) -N-methylcarbamate used as the starting material in the above preparation became as follows manufactured:

A solution of 2 ml of sulfuryl chloride in 20 ml of anhydrous chloroform was converted into a solution of 5 g of phenyl-N ~ methyl-N- (thiazol-2-yl) carbamate in 50 ml of anhydrous chloroform at ⁰ ° C. within half an hour Stirring added. The reaction mixture was left to stand at 15 ° C. for 20 hours and then washed successively with aqueous 2N sodium bicarbonate solution and with water. The organic layer was separated and evaporated under reduced pressure to give crude phenyl-N-methyl-N-

10 9 8 17/2277

(5-chlorothiazol-2-yl) carbamate was obtained from F = 104-1O6 ° C, which was recrystallized twice from a mixture of acetone and petroleum ether (boiling range: 60-80 ° C). This gave 1.5 g of phenyl-N-methyl-N- (5-chloro-thiazol-2-yl) carbamate νοτη F = 119 ⁰ C.

The phenyl-N-methyl-N- (thiazol ~ 2-yl) carbamate used as the starting material in this preparation was made as follows:

g of phenyl chloroformate were added over the course of 1 hour to an ice-cooled, mechanically stirred solution of 228 g of 2-methylaminothiazbl in 1.2 l of anhydrous pyridine. The reaction mixture was stirred for a further 2 hours without cooling and then left to stand at room temperature overnight. After filtering, the solid portion of the reaction mixture was washed successively with 200 ml of water, 75 ml of 2N hydrochloric acid and 100 ml of water and dried over silica gel in vacuo. 20 g of an impure product (A) with a melting point of 55 ° -80 ° C. were obtained. The liquid part of the reaction mixture was slowly added to 3 liters of ice water while stirring by hand. A somewhat sticky solid substance separated itself and was rapidly hardened and collected on further stirring, washed successively with 650 ml of water, 500 ml of 2N hydrochloric acid and 650 ml of water and dried initially in air and finally in vacuo over silica gel. In this case were 425 g of a product (B) from F = 78 to 81 ⁰ C after initial sintering obtained. All of the aqueous liquids obtained in isolating the product (B) were combined and, upon standing for 2 days, gradually deposited another solid matter, which was collected, washed with water and dried. Here, 16 g of a product (C) from F = 78-87 ⁰ C according to the preceding sintering obtained.

Product (A) was sieved through a 4o-mesh sieve and stirred with 30 ml of diethyl ether and the solid matter was filtered off, washed on the filter with 50 ml of diethyl ether and dried. The solid obtained (9 g) from F = 84-85 ⁰ C was combined with the products (B) and (C) and the whole was passed through a 40 mesh sieve overall

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sieves and stirred with 400 ml of cyclohexane. After filtering, the residue on the filter was washed with 600 ml of cyclohexane and air dried. This gave 495 g of phenyl N-methyl-N- (thiazol-2-yl) carbamate in the form of a pale yellow crystalline powder from F = 82 - 85 ° C, which is for further use was sufficiently pure as an intermediate or starting product.

Example 14 1- (5-chlorothiazol-2-yl) ~ l, dimethyl urea

An excess of ethanolic 50% (w / w) monomethylamine solution was added to a small sample of N- (5-chlorothiazol-2-yl) N-methyl-carbamoyl chloride (about 100 mg) dissolved in ethanol (about 5 ml ), admitted. The reaction mixture was left to stand at 15 ° C. for 16 hours. The ethanol was then removed by evaporation under reduced pressure, l- (5-chlorothiazol-2-yl) -l, 3-dimethylurea having an melting point of 115 ^° C. being obtained.

The N- (5-chlorothiazol-2-yl) -N-methylcarbamoyl chloride used as the starting material in the above preparation became as follows manufactured:

A solution of 6.2 g of chlorine in 100 ml of 1,2-dichloroethane was (as described in Example 7) to a solution of 15 W "38 g N-methyl-N- (thiazol-2-yl) carbamoyl chloride in 100 ml of 1,2-dichloroethane were added and the reaction mixture was left to stand at 17 ° C. for 1 hour. The precipitated solid was filtered off, washed with a little cold 1,2-dichloroethane and dried in vacuo. 8.35 g of N- (5-chlorothiazol-2-yl) -N-methylcarbamoylchlorld with a melting point of 98 ° C. were obtained in this way.

Example 15 1,3-Dimethyl-1- (5-.1odthiazol-2-yl) urea

A solution of 10.27 g of 1,3-dimethyl 1-3 ^ (thiazol-2-yl) urea (prepared as described in Example 1) in a mixture of 90 ml of ethanol, 12 ml of concentrated sulfuric acid and 75 ml of water

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was added within 15 minutes to a solution of 8–7 g of potassium iodide and 5.49 g of potassium iodate in 150 ml of water at 55 ° C. with stirring. The reaction mixture was then stirred ^{at 52 to 58 ° C. for a further 45 minutes.} The solution was decanted so that, as far as possible, some tarry material which had separated was removed, filtered while warm and cooled, and the precipitate formed was filtered off. 7 * 51 g of 1,3-dimethyl-1- (5-iodothiazol-2-yl) urea with a P = 150-155 ° C. were obtained in this way. Concentration of the filtrate gave a second fraction of the product ... (2.34 g) melting at 147-151 ° C. " The two fractions were combined and recrystallized from a mixture of equal volumes of benzene and twice Petroleum benzine (boiling range 80-100 ⁰ C) recrystallized. 6 * 5 gl, 3-dimethyl-1- (5-iodothiazol-2-yl) urea with a melting point of 155-155 ° C. were obtained.

Example 16
1- (5-iodothiaz.ol -2- yl) -l, 3-dimethyl urea

A solution of 437 g of iodine monochloride in glacial acetic acid (volume of the solution: 1986 ml) was stirred within 1 1/2 hours to a solution of 184.4 g of 1,3-dimethyl-l .- (thiazol-2-yl ) urea, prepared as described in Example 1, added in 1 liter of glacial acetic acid, the temperature of the reaction mixture not being allowed to rise above 25 ^° C. The reaction mixture was then stirred for 3 hours at room temperature, "The deposited yellow solid was filtered, washed with petroleum ether (boiling range 40 - 60 ⁰ C) and dried, whereby 415 g of a solid substance were obtained. By adding 2 liters of petroleum ether (boiling range: 60-80 ° C.) to the filtrate and allowing it to stand overnight, a further amount of 39 g of a somewhat darker material was obtained. The two fractions were combined, suspended in 1 liter of water and decolorized by adding sodium metabisulphite (4 times 50 g) in the minimum amount of water. The now cream-colored solid material was filtered off, washed with water, sucked dry on the filter and then suspended in 1.5 liters of aqueous saturated sodium bicarbonate solution. After stirring for 11/2 hours, the suspended solid was filtered off

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(ft)

and dried in vacuo over silica gel, whereby 262 g of impure i- (5-iodothiazol-2-yl) -l, 3-dimethylurea with a melting point of 148 15 ¹ I ⁰ C were obtained, which was obtained from a mixture of equal volumes of benzene and petroleum benzine ( Boiling range: 80-100 C) was recrystallized. This gave 225 S l- (5-Jodthiazol-2-yl) -l, 3-dimethylurea by F = 152-154.5 ⁰ C.

Example 17 1- (5-Bromothiazol-2-yl) -l-ethyl-3-methylurea

A solution of 3 * 05 ml of bromine in 5 ml of glacial acetic acid was added dropwise P to a mechanically stirred solution within 30 minutes of 11.1 g of l-ethyl-j5-methyl-l- (thiazol-2-yl) urea (prepared as described in Example 4) added in 30 ml of glacial acetic acid, which was kept at a temperature below 10 C by cooling in ice water. The reaction mixture was then at room temperature stirred for a further 15 minutes. The deposited solid substance was filtered off, washed on the filter with a little glacial acetic acid and then with anhydrous diethyl ether and in vacuo dried over silica gel. The solid product (15 g) was washed with excess aqueous saturated sodium bicarbonate solution triturated and the off-white insoluble solid material was collected, washed with a little water and in vacuo fc dried over silica gel. This gave 9.2 g of 1- (5-bromothiazol-2-yl) -l-ethyl-3-methylurea obtained from F = 124-125 ° C.

Example 18 1- (5-chlorothiazol-2-yl) -l-ethyl-3-methylurea

A solution of 4.5 ml of sulfuryl chloride in 20 ml of anhydrous chloroform was converted into a solution of 9 * 25 g of 1-ethyl-3-methyl-1- (thiazol-2-yl) urea (prepared as in Example 4) was added in 30 ml of anhydrous chloroform with stirring, the temperature of the reaction mixture being kept below 26 ^° C. The solution was then evaporated to dryness and the residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. the

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The ethyl acetate phase was separated off and dried over sodium sulfate, and the ethyl acetate was evaporated under reduced pressure. 9.44 g of crude 1- (5-chlorothiazol-2-yl) '- ethyl-3-methylurea with a P = 103 ° -118 ° C. were obtained in this way, from. Cyclohexane was recrystallized and thereby 4.15 g of l- (5-Chlorthiazoi-2-yl) -l-ethyl-3-methylharnstqff from F - 123,5- -125.5 ° C afforded.

Example 19 1- (5-iodothiazol-2-yl) -l-ethyl-3-methyl- urea

A solution of 39 * 0 g of iodine monochloride in glacial acetic acid (volume of Solution: 180 ml) became a Solution of 14.8 g of l-ethyl-3-methyl-l- (thiazol-2-yl) urea (prepared as described in Example 4) added in 80 ml of glacial acetic acid, the temperature was not allowed to rise above 15 ° C. The reaction mixture was then left at room temperature for 3 hours touched. The deposited yellow pest substance (31 * 9 g) was filtered off in a solution of 12 g of sodium metabisulphite Suspended 100 ml of water, stirred for 15 minutes and filtered off. This filtered precipitate was washed with water and water then in 100 ml of aqueous saturated sodium bicarbonate solution suspended, stirred for 2 hours and filtered. In this way 17 * 3 g of crude 1- (5-iodothiazol-2-yl) -l-ethyl-3-methyl-urea from F = 106-109 ° C obtained, which was recrystallized from cyclohexane to 15.5 g of l- (5-iodothiazol-2-yl) -l-ethyl-3-methy! Urea vom F = 111-112 ° C to give.

Example 20 1- (5-bromothiazol-2-yl) -1,3,3-trimethyl urea

A solution of 79 ml of bromine in 500 ml of anhydrous chloroform was added dropwise over the course of 75 minutes to a mechanically stirred solution of 286 g of 1- (thiazol-2-yl) -l, 3,3-trimethyl urea in 500 ml of anhydrous chloroform , the solution being kept at a temperature below 10 ^{° C. by cooling in ice water.} After the addition was complete, the reaction mixture was heated to ⁰ ° C.

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cooled and then added within 75 minutes to 2.6 l of ice-cold anhydrous diethyl ether with thorough stirring. The precipitated, somewhat sticky, slightly brown powdery substance was collected and air-dried. After sieving through a 40 mesh sieve, this solid (503 g) was stirred with 500 ml of anhydrous acetone. The insoluble solid was separated, washed with acetone and air dried. The beige colored solid substance obtained (465 g) was then gradually added to 2 liters of distilled water with thorough stirring. After the addition was complete, stirring was continued for an additional hour. The insoluble solid was then collected, washed thoroughly with water / water (500 ml twice) and dried first in air and then in vacuo over silica gel. There were thus 275 g of l- (5-Bromo-thiazol-2-yl) -1,3,5-trimethylurea in the form of an off-white solid of F = 68 - 69 ⁰ C obtained.

The treatment of the combined aqueous mother liquor and washing liquids with a sufficient amount of aqueous 2N sodium carbonate solution (1.25 1)> to bring the pH to 7, separation of the precipitated solid matter, washing with water and drying initially in air and then in vacuo over silica gel yielded a second fraction of 36 g of slightly less pure l- (5-Dromthiazol-2-yl) -l, 3,3-trimethylurea from F = 68 - 69 ⁰ C.

^ The one used as the starting material in the above manufacture 1- (Thiazol-2-yl) -l, 3,3-trimethylurea was prepared as follows:

415 g phenyl-N-methyl ~ N- (thiazol-2-yl) -carbamate (manufactured as described in Example 13) were in 800 ml of anhydrous benzene suspended, and 400 g of dimethylamine were added while cooling with ice. The resulting solution was divided into portions and divided into Pressurized glass bottles were introduced, which were then sealed. The pressure bottles were then left on a steam bath for 12 hours heated. The contents of the pressure bottles were then combined and the combined solutions were subjected to steam distillation, until all of the phenol was removed (12 liters of distillate were

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.collects). Most of the water in the reaction mixture was then reduced by distillation on a steam bath Pressure (20 mm Hg) removed. The remaining oil was in Dissolved methylene chloride and the resulting solution under atmospheric Pressure distilled to dryness. Remaining traces of methylene chloride were removed by heating on a steam bath removed under reduced pressure (20 mm Hg). It was 286 g l- (Thiazol-2-yl) -l, 3i3- "fcrimethylurea in the form of a brown Obtained oil, which is used as starting material without further purification became. ·. .

Alternative processes used for the preparation of 1- (thiazol-2-yl) -1,3 * 3-trimethylurea suitable as starting material are the following:

(a) 1.5 g of sodium hydride was added to a solution of 8.55 S. 1,3-Dimethyl-l- (thiazol-2-yl) urea (prepared as in example 1) in 40 ml of dimethylformamide was added, and the mixture was stirred at room temperature for 24 hours. X 4.25 ml Methyl iodide was then added to the solution and stirring continued for another 15 minutes. The solvent was then removed by evaporation and the solid residue extracted with diethyl ether. The ether extracts were dried over sodium sulfate and concentrated. It was 6.0 g Obtained l- (Thiazol-2-yl) -l, 3,3-trimethylurea in the form of an orange-red oil.

(b) 5.1 ml of an aqueous 40 # (weight per weight) dimethylamine solution was added with stirring to a solution of 4.0 g of N-methyl-N- (thiazol-2-yl) -carbarr.oyl chloride (prepared as in Example 7 described) added in 5 ml of acetone. An exothermic reaction occurred and stirring was continued for 15 minutes. The acetone and water were then evaporated under reduced pressure. The residue was then with 50 ml Diethyl ether extracted and filtered, and the solid was washed with a further amount of diethyl ether. The ether extract and the wash fluids were combined and submerged

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Evaporated under reduced pressure, leaving 3 * 4 g of l- (thiazol-2-yl) -1,3,3-trimethylurea in the form of a brown oil.

(c) A mixture of 5.7 g of 2-methylaminothiazole, 5.0 g of triethylamine and 30 ml of anhydrous toluene were added within 2 hours to a mechanically stirred solution of phosgene (20 ml, measured at -20 ° C.) in dry toluene (30 ml), by external cooling in a dry ice / acetone bath at 0 - 5 ⁰ C was added held. The reaction mixture was then allowed to stand at room temperature for 3 days and unreacted phosgene was removed in a stream of dry nitrogen. The Reaktionsgemjs ch was filtered, and a solution of dimethylamine (10 ml, measured at -20 ⁰ C) in dry toluene (25 ml) was then added to the mechanically stirred, ice-cooled filtrate. After standing overnight at room temperature, the reaction mixture was filtered off and the toluene was removed from the filtrate under reduced pressure on a rotary evaporator. This gave 3.1 g of 1- (thiazol-2-yl) -1,3,3-trimethylurea in the form of a brown oil.

Example 21

1- (5-bromothiazol-2-yI) -I, 3,3-trimethyl urea

A solution of k, 0 gPhenyl-N- (5-bromothiazol-2-yl) -N-methylcarbamate and 1.44 g of dimethylamine in 60 ml of anhydrous benzene was at room temperature in a sealed flask allowed to stand for 2 days. The reaction mixture was then subjected to steam distillation until there was no more phenol in the distillate. The aqueous solution that remained was concentrated in vacuo and gave 2 g of a white solid which was dissolved in 100 ml of 2N hydrochloric acid. The pH of the solution was brought by addition of solid sodium bicarbonate to 4, and the precipitate was filtered and recrystallized from petroleum ether (boiling range: 60 - 8O ⁰ C) recrystallized. There were thus 1.2 g of l- (5-Bromo-thiazol-2-yl) -1,3,2-trimethylurea from F = 67 - 68 ⁰ C obtained.

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'6S

That used as the starting material in the above manufacture Phenyl N- (5-bromothlazol-2-yl) -N-methylcarbamate was obtained as follows:,

A solution of 4.56 ml of bromine in 20 ml of chloroform was added dropwise to a mixture of 20 g of phenyl N-methyl-N- (thiazol-2-yl) carbamate (prepared as described in Example 5 or 13) and 20 g Calcium carbonate in 400 ml of chloroform was added with stirring. The reaction mixture was stirred for an additional hour and then filtered. The filtrate was washed twice in succession with 50 ml of aqueous 2N sodium bicarbonate solution and 50 ml of water each time, dried over sodium sulfate and evaporated. There were thus 25 * 07 g of phenyl N- (5-bromothiazol ~ 2-yl) -N-methylcarbamate P = 114 - 116 ⁰ C obtained.

Example 22

1- (5-brorofluorothiazol-2-yl) -1,3,3-trimethyl urea

2.25 ml of an aqueous 40% (weight per weight) dimethylamine solution were added with vigorous stirring to a solution of 2.6 g of N- (5-bromothiazol-2-yl) -N-methylcarbamoyl bromide (prepared as in Example 8) was added in 15 ml of acetone. Stirring was continued for 15 minutes at room temperature and the acetone was then removed under reduced pressure. The precipitate was filtered off, washed thoroughly with water, dried in vacuo over silica gel and recrystallized from aqueous acetone. There were thus 2.0 g of l- (5 ~ Bromo-thiazol-2-yl) -l, 3,3-trimethylurea in the form of fine white needles, P = 67.5 to 7O ⁰ C. were obtained.

Example 23

1- (5-BromothiazQl-2-yI) -I, 3,3-trimethyl urea

A solution of 12.5 g of 1- (5-bromothiazol-2-yl) -l, 3-dimethylurea (prepared as described in Example 1, 2> 6, 7 or 8) in 20 ml of anhydrous dimethylformamide was within 2 hours to a mechanically stirred. Mixture of 4.25 ml

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Methyl iodide and 1.5 g sodium hydride in 40 ml anhydrous dimethylformamide admitted. The reaction mixture was stirred overnight, the solvent removed and the residue that remained Solid substance was extracted with chloroform. The chloroform extract was dried over sodium sulfate and concentrated, and the residue was obtained from petroleum ether (boiling range: 6o - 80 ° C) recrystallized. 7.5 g of 1- (5-bromothiazol-2-yl) -1,3,3-trimethylurea were obtained in this way from F = 67 - 68 ° C.

According to the above procedure, but with the replacement of the 1- (5-bromothiazol-2-yl) -1, 3-dimethy! Urea by 1- (5-chlorothiazol-2-yl) -1, 3-dimethylurea (prepared as described in Example 11, ';<>, 13 or 14) and by replacing the methyl iodide with ethyl iodide or n-propyl iodide, l- (5-chlorothiazol-2-yl) -l, 3-dimethyl-> ethylurea and l- ( 5-chlorothiazol-2-yl) -l, 2-dimethyl-3n-propylurea obtained.

Example 24

1- (5-bromothiazol-2-yl) -1,3,3-trimethyl urea

A solution of 4.72 g of 1- (5-bromothiazol-2-yl) -3-methylurea in 20 ml of anhydrous dimethylformamide was converted into a mechanically stirred mixture of 2.5 ml of methyl iodide and 1 g of sodium hydride in 20 ml over the course of 2 hours anhydrous dimethylformamide added. The reaction mixture was stirred overnight, the solvent was removed in a stream of warm air and the solid residue was extracted with diethyl ether. The ether extracts were dried over sodium sulfate and concentrated and the residue was recrystallized from petroleum ether (boiling range: 60-80 ° C.). There was thus 1 g of l- (5-Bromo-thiazol-2-yl) -l, 3,3-trimethylurea from F = 67-68 ⁰ C.

The 1- (5-bromothiazol-2 ~ yl) -j5-methylurea used as starting material in the above preparation can be prepared according to one of the following procedures can be obtained:

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(a) A solution of 2.85 g of methyl isocyanate in 10 ml of anhydrous acetone was added to a solution of 8.95 g of 2-amino-5-bromothiazole- (prepared according to English et al. J. Amer. Chem. Soc, 1946 , 68, 457) in 25 ml of anhydrous acetone was added, during which time the temperature rose from 18 to 28 ° C. The mixture was then stirred at 60-65 ⁰ C (bath temperature) for one hour under reflux and cooled. The deposited white pest substance was separated off, washed with a little acetone and dried, 4.6 g of 1- (5-bromothiazol-2'yl) -5-methylurea being obtained. A sample was crystallized from ethanol to give a material with an F = 204 ° C (dec.). ,

(b) A suspension of 83 g of 3-Methy1-1- (thiazol-2-yl) -urea in 500 ml of anhydrous chloroform was kept under stirring at 20 ⁰ C (by external cooling with water as necessary), while - A solution of 26.3 ml of bromine in 50 ml of anhydrous chloroform was added for 3 hours. No solid phase was present halfway through the addition. After the addition had ended, the mixture was stirred for a further 11/2 hours at room temperature. The insoluble material was separated off, washed with chloroform and dried in vacuo over silica gel, giving 77 g of 1- (5-bromothiazol-2-yl) -3-methylurea hydrobromide, melting point 192-195 ° C. (decomp.) . This material was then thoroughly triturated with excess aqueous saturated sodium bicarbonate solution and the insoluble solid was separated, washed thoroughly with water and dried. 49 g of 1- (5-bromothiazol-2-yl) -2-methylurea were obtained in the form of a brown-yellow solid. A sample was crystallized from methylcellusolve to give a material of F = 206 ° C (dec.).

Example 25

1- (5-chlorothiazol-2-yI) -I, 3,3-trimethyl urea

A solution of 13.6 ml of sulfuryl chloride in 15 ml of dry chloroform was within 15 minutes to a mechanically stirred ice-cold solution of 27 g of l- (thiazol-2-yl) -l, 3,3-trimethyl-

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urea (prepared as described in Example 5 or 20) in 100 ml of dry chloroform was added. The reaction mixture was Left overnight at room temperature, remove the chloroform by evaporation under reduced pressure on a rotary evaporator (Bath temperature 35 ° C) removed and the brown greasy residue taken up in 75 ml of ethanol. The ethanol solution was diluted with 120 ml of anhydrous diethyl ether and continued with If a fawn-colored solid substance separates, it is washed thoroughly with acetone and dried in vacuo over silica gel became. The solid substance obtained (15 * 5 g)> F = 133 - 135 C, was dissolved in a little water, and the resulting dark colored solution was diluted with 250 ml of water and washed thoroughly with it Diethyl ether extracted. The almost colorless ether extracts were washed successively with water, aqueous sodium bicarbonate solution and water and dried over magnesium sulfate. By evaporation of the diethyl ether, finally in vacuo over silica gel, 9 * 5 g of l- (5-chlorothiazol-2-yl) -1,3,3-trimethylurea in Preserved the form of a golden yellow oil.

Example 26 1- (5-iodothiazol-2-yl) -l, 3> 3-methyl-urea

A solution of iodine monochloride in acetic acid (110 ml containing 24.2 g of iodine monochloride) was added dropwise within "of 45 minutes to a solution of 14.1 g of 1- (thiazol-2-yl) -l, 3.3 ~ trlmethylurea (prepared as described in example 5 or 20) in 15 ml of glacial acetic acid, which is cooled in a cold water bath was added with good stirring. Stirring was continued at room temperature for an additional 16 hours. The reaction mixture was then left to stand, and the clear supernatant Liquid was decanted off. The dark colored insoluble residue was dissolved with a mixture of 100 ml of water, 30 g of sodium metabisulfite and shaken 150 ml of methylene chloride. The organic layer was separated and the methylene chloride evaporated left, with 16 g of crude 1- (5-iodothiazol-2-yl) -1,3,3-trimethylurea in the form of a pale yellow solid substance with a melting point of 118 121 ° C obtained after softening at 115 ° C. Through treatment

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with decolorizing charcoal and recrystallization from 18O ml of cyclohexane 13 g of 1- (5-iodothiazol-2-yl) -l, 3,3-trimethylurea were obtained in the form of shiny white platelets with an temperature of 123-125 ° C.

Example 27
1- (5 ~ bromothia2ol-2-yl) -l-ethyl-3,3 ~ dlmethylurestoi'f

A solution of 22.7 g of 1-ethyl-3-methy1-1- (thiazol-2-yl) urea (prepared as described in Example 4) in 55 ml of dimethylformamide was stirred into a mixture of 50 within half an hour ^ igen (weight per weight) suspension of sodium hydride in oil (containing 7.36 g of sodium hydride) in 35 ml of dimethylformamide with cooling in a water bath in order to keep the temperature at about 25 ° C Stirred for hour, and 11 ml of methyl iodide were then added over the course of half an hour. Stirring was continued for 3 hours. The deposited solid was filtered off. The filtrate was evaporated to constant weight under reduced pressure, and the non-volatile residue was taken up in 100 ml of 2N hydrochloric acid. The acid solution was extracted with benzene. The aqueous layer was neutralized with solid sodium bicarbonate and extracted with diethyl ether. Evaporation of the diethyl ether gave 12.8 g of a dark brown oil which was then dissolved in 30 ml of chloroform. A solution of 3 Λ ml of bromine in 10 ml of chloroform was added to the chloroform solution over half an hour with stirring, the temperature of the reaction mixture being kept below 35 ° C. Then some sodium metabisulfite was added to the reaction mixture with stirring to remove excess bromine, and the reaction mixture was filtered and the chloroform removed in vacuo. The residue was taken up in diethyl ether and saturated aqueous sodium bicarbonate solution. The Ktherschieht was separated and the ether removed to give 14.6 g of a dark brown oil were obtained, which in petroleum ether (boiling range 60-80 ⁰ C) was dissolved. The solution was chromatographed on aluminum oxide (100 g in a column 2 cm in diameter), which eluted with benzene / diethyl ether

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Fraction was collected and distilled. The main fraction (3 * 87 g), bp ₀ «p = 1O3 ° C, crystallized to a solid substance of F = 61-65" C ₁ which was recrystallized from petroleum ether (boiling range: 60-80 ° C). This gave 2 , 73 g of l- (5-Bromo-thiazol-2-yl) -l-ethyl-3,3-dimethylurea by F = 65.5 to 67.5 C ⁰

Using the procedure described above, but replacing the bromine with sulfuryl chloride, 1- (5-chlorothiazol-2-yl) -l ~ ethyl-3,3-dimethylurea was obtained obtain.

Example 28
"L- (5-bromo thiazole-2-yl) -l _J 3-dirnethyl-3-ä thy lharnst off

A solution of 4 ml of bromine in 20 ml of anhydrous chloroform was added over the course of 1 hour to a mechanically stirred solution of 14 g of 3-dimethyl-3-ethy1-1- (thiazol-2-yl) urea in 30 ml of anhydrous chloroform and stirring was continued for an additional hour. The chloroform was then removed and the residual oil treated with aqueous saturated sodium bicarbonate solution. The oil was purified by dissolving in petroleum ether (boiling range: 60-80 ° C.) and by column chromatography on silica gel (60 g in a column 2 cm in diameter). The fractions eluted with petroleum benzine (boiling range 80-100 ° C.) / 10% ethyl acetate were combined and distilled, with J>, 2 g of 1- (5-bromothiazol-2-yl) -l, 3-dimethyl-3-ethylurea with a bp _{Q χ} = 124 - 126 ° C.

The l, 3-dimethyl ~ 3-ethyl-l- (thiazol-2-yl) urea used as starting material in the above preparation can be according to the following processes can be produced:

(a) A mixture of 17.1 g of 1,3-dimethyl-1- (thiazol-2-yl) urea (prepared as in Example 1) and 3 g of sodium hydride in 80 ml of dry dimethylformamide was stirred at room temperature for 24 hours. A solution of 7 * 5 ml of ethyl bromide in 20 ml of dry dimethylformamide was added then sets within 20 minutes, and stirring was continued for another 30 minutes. The solvent was removed and the residue with diethyl ether

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extracted. The ether extracts were dried over sodium sulfate and narrowed. There were so Hg 1,3-dimethyl-; 5-ethyl-l- (thiazol-2-yl) urea obtained in the form of a reddish oil.

(b) A solution of 28.8 g of ethyl isocyanate in 50 ml of acetonitrile became a mechanically stirred solution in 150 minutes of 45.2 g of 2-methylamino-thiazole and 0.5 ml of triethylamine in 200 ml of acetonitrile was added, and the reaction mixture was refluxed for 4 hours. The solvent was then removed, with 70.6 g of 3-ethyl-l-methyl-l- (thiazol-2-yl) urea were obtained in the form of a red oil. 37 g of this Oil was mixed with 6 g of sodium hydride in 80 ml of anhydrous dimethylformamide mixed and stirred for 24 hours at room temperature. A solution of 18 ml of methyl iodide in 20 ml of anhydrous dimethylformamide was then added over 20 minutes and the reaction mixture was stirred at room temperature for 1 hour. The solvent was then removed and the residue with diethyl ether extracted. The ether extract was dried and concentrated. 29.6 g of 1,3-dimethyl-3-ethyl-l- (thiazole- -urea in the form of an oil.

Example 29

1- (5-bromothiazol-2-yl) -1,3-dimethyl- ^ n-propylurea

A solution of 4.9 g of bromine in 40 ml of anhydrous chloroform was added dropwise and with stirring at 0 ^° C. to a solution of 6.5 g of 3-dimethyl-3-n-propyl-l- (thiazol-2-yl) -urea added in 40 ml v / water-free chloroform. The ice bath was then removed and the reaction mixture was stirred for 4 hours. The chloroform and unreacted bromine were removed by evaporation under reduced pressure. The orange-colored viscous oil obtained crystallized on standing overnight in the refrigerator. The solid substance was triturated with acetone, with 8.2 g of 1- (5-bromothiazol-2-yl) ~ 1,5-dimethyl-3-n-propyr-urea hydrobromide in the form of a white solid substance with an F = 126-127 , 5 ° C, which was then partitioned between 50 ml of diethyl ether and 20 ml of water. The ether extract was washed three times with 10 ml of water each time and

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dried over sodium sulfate. The diethyl ether was reduced Pressure evaporated and the residue at 30 ° C / 0.1 mm Hg heated. There were thus 5 * 9 S 1- (5-bromothiazol-2-yl) -1, J-dimethyl-3> -n-propy Obtain urea in the form of a colorless viscous oil.

The 1,5-dimethyl-> n-propyl-1- (thiazol-2-yl) urea used as starting material in the above preparation was made up of the following V / way received:

3.1 g of granular sodium hydride were slowly added with stirring at -5 ° C. to a solution of 19.9 S of 1-methyl-3-n-propy 1-1- (thiazol-2-yl) urea in 80 ml of anhydrous dimethylformamide admitted. The reaction mixture was then stirred for 1 hour at OC and then and stirred for 2h hours to reach room temperature. The solution was decanted from trace amounts of unreacted sodium hydride, and 8.6 ml of methyl iodide were then added dropwise with stirring and cooling to maintain the temperature at 15 - added to maintain 20 ⁰ C. After stirring for 4 hours at room temperature, the mixture was filtered to remove the precipitated sodium iodide. By distillation in vacuo was removed first, the dimethylformamide and then 6.5 g of 1,3-Dimothylj5-n ~ propyl-l- (thiazol-2-yl) -urea was a pale yellow oil, bp = _{0 ol} HO ⁰ C in the form of .

The l-methyl-J-n-propyl-l- (thiazol-2-yl) urea became as follows manufactured:

A solution of 8.5 g of n-propyl isocyanate in 75 ml of anhydrous Acetone was added dropwise with stirring to a solution of 11.4 g 2-Methylauiinothiazole was added in 50 ml of anhydrous acetone. After refluxing for 15 hours, the solution was evaporated under reduced pressure, giving 19.9 S 1-methyl-5-n-propyl-^ - (thiazol-2-yl) urea in the form of a viscous golden oil that can be used as a starting material without further purification was used.

According to a further feature of the invention, assemblies

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.ffr.

Settlements which are suitable for herbicidal use are created which contain one or more of the thiazole derivatives of the general formula II or agriculturally useful acid addition salts of these together with and preferably homogeneously dispersed in one or more compatible diluents or carriers (ie diluents or carriers of the type generally recognized as being suitable for use in herbicidal compositions which are compatible with the compounds of the general formula II or agriculturally useful acid addition salts thereof). The term "homogeneously dispersed" is intended to include compositions in which the compounds of the general formula II are dissolved in the other components. The term "herbicidal compositions" is used in a broad sense and includes not only compositions ready for use as herbicides but also concentrates which must be diluted before use. Preferably, the compositions contain from 0.05 - 90 wt -.% Of compounds of the general formula II or an agriculturally acceptable acid addition salts.

The herbicidal compositions can be both a diluent or a carrier as well as a surface active agent, (e.g. a wetting agent, dispersant or emulsifier) contain. Surface-active agents which can be present in the herbicidal compositions according to the invention, can be of the ionic or non-ionic type, such as Sulforicinoleate, quaternary ammonium derivatives, products on the basis of condensates of ethylene oxide, such as condensates of ethylene oxide with nonyl or octyl phenols, or Carboxylic acid esters of anhydrosorbites obtained by etherification of the free hydroxyl groups are made soluble by condensation with ethylene oxide, alkali and alkaline earth salts of * sulfuric acid esters and sulfonic acids such as dinonyl and dioctyl sodium sulfosuccinates and Alkali and alkaline earth salts of sulfonic acid derivatives high molecular weight such as sodium and calcium lignosulfonates. Examples of suitable solid diluents or carriers are aluminum silicate, talc,

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calcined magnesia, kieselguhr, tricalcium phosphate, cork powder, Adsorption carbon or soot and clays such as kaolin and bentonite. The solid compositions (which are in the form of Dusts, granules or wettable powders may be present) are preferably prepared by grinding compounds of the general formula II or their agriculturally useful acid addition salts with solid diluents or by Impregnation of the solid diluents or carriers with solutions of compounds of the general formula II or their agriculturally usable acid addition salts in.volatile solvents, evaporation of the solvents and if necessary Crushing the products to obtain powder made. Granule preparations can by absorption of the compounds of the general formula II or of the agriculturally useful acid addition salts of these (dissolved in volatile solvents) on the solid diluents or carriers in granular form and evaporation of the solvents or by granulating compositions obtained as described above in powder form. Solid herbicidal Compositions, particularly wettable powders, can Contain wetting agents or dispersants (for example of the types mentioned above), which, if they are solid, also as Diluents or carriers can serve.

Liquid compositions according to the invention can be in the form of aqueous, organic or aqueous-organic solutions, suspensions and emulsions which may contain a surfactant are present. About suitable liquid diluents for incorporation into the liquid compositions include water, acetophenone, cyclohexanone, isophorone, toluene, Xylene and mineral, animal and vegetable oils (and mixtures these diluents). The surfactants can be ionic or non-ionic (e.g. those of the types mentioned above) and, if they are liquid, can also serve as diluents or carriers. If so desired liquid compositions of the compounds of general formula II

109817/2 2 27

be used in the form of self-emulsifiable concentrates, which contain the active substances, dissolved in the emulsifiers or in solvents, which are compatible with the active substances Contain emulsifiers, whereby- the simple addition of V / water to such concentrates enable ready-to-use compositions to obtain.

Herbicidal compositions according to the invention can also be desired if necessary, usual adjuvants, such as adhesives, Colorants and corrosion inhibitors, contain * These adjuvants can also serve as carriers or diluents.

Herbicidal compositions according to the invention can also use the compounds of the general formula II or their agriculturally useful acid addition salts together with and preferably homogeneously dispersed in one or more other than pesticides active compounds and if desired one or more diluents or carriers, surface active agents and useful in pesticides customary adjuvants as described above contain. For examples for other compounds which are effective as pesticides and which are in the herbicidal compositions according to the invention can be included or can be used together with the herbicidal compositions according to the invention, include herbicides such as phenoxy alkanoic acids [e.g. 4- (4-chloro-2-methylphenoxy) butyric acid, 4- (2,4-dichlorophenoxy) butyric acid, 2- (4-chloro-2-methylphenoxy) propionic acid, 2- (2,4-dichlorophenoxypropionic acid, 4-chloro-2-methy! Phenoxyacetic acid, 2,4-dichlorophenoxy-acetic acid and 2,4,5-trichlorophenoxy-acetic acid], Benzoic acid derivatives (e.g. 2,5,6-trichlorobenzoic acid, 2-methoxy-j5,6-dichlorobenzoic acid and 3-amino-2,5-dichlorobenzoic acid), halogenated aliphatic acids (e.g. trichloroacetic acid and 2,2-dichloropropionic acid), carbamates [e.g. Isopropyl N- (5-chlorophenyl) carbamate, isopropyl N-phenyl carbamate and 5-chloro-2-butynyl-N- (5-chlorophenyl) carbamate], thiocarbamates (e.g. S-2,3,5-Trichlorallyl-N, N-diisopropylthioearbamate and S-propyl-NjN-dipropylthiocarbamate), amides [e.g. 5.4 Di

10 9 8 17/2227

chlorpropion anilide, 2-chloro-N-isopropylacetanilide and DN-ethyl-2- (phenylcarbamoyloxy) propionamide], urea derivatives [e.g. N- (4-chlorophenyl) -N, N-dimethylurea, Ν, Ν-dimethyl-N ' -pheny 1 · - urea, N '- (3,4-dichlorophenyl) -N _i N-dimethylurea and N' - (4-chlorophenyl) -N-methoxy-N-methylurea], diazines (e.g. 5-bromo-j5 -isopropyl-6-methyl-uracil and I-cyclohexyl-Siß-trimethyleneuracil), triazines [e.g. 2-chloro-4,6-bis-ethylamino-1, j5 * 5-triazine, 2-chloro-4-ethylamino-6 -Isopropylamino-l, j5,5-triazine and 6- (j5-methoxypropylamino) -4-isopropylamino-2-methylthio-1,2,5-triazine], substituted phenols [e.g. 2-methyl-4,6. -dinitro ~ phenol, 2- (1-methylpropyl) -4,6-dinitrophenol and 2,4-dichlorophenyl-4-nitrophenyl ether], quaternary ammonium derivatives (e.g. 1,1 * -ethylene-2,2 ¹ -bipyridylium- and 1 , 1 '-dimethyl-4,4'-dipyridyliurfisalze), benzonitrile derivatives (for example 2,6-dichlorobenzonitrile and ~ j>, 5-Di iodine and ~ $, 5-dibromo-4-hydroxybenzonitrile and their esters, for example, their octano -Dibromo-4-hydroxybenzonitrile and the en esters, e.g. their octanoates), triazole derivatives (e.g. 3-amino-l, 2,4-triazole), ihiocarbonyl derivatives [e.g. dimethoxythiocarbonyl) disulphide] , benzenesulphonylcarbamates (e.g. methyl 4-aminobenzenesulphonylcarbamate * Mothy1-4-nitrobenzenesulphonyl Methyl-4-methoxy-carbonylatnobenzenesulphonylcarbamate), 4-chloro - ^ - oxo-benzothiazoline-Jy! -Acetic acid and 2-tert. "Butyl-4- (2,4-dichloro-5-isopropyloxyphenyl) -5-oxo-1 , 3 * 4-oxadiazole, insecticides such as naphth-1-yl-N-methylcarbamate, and fungicides such as 2,6-dimethyl-4-tridecylmorpholine, methyl-N-benzimidazol-2-yl-N- (butylcarbamoyl ) carbamate and 1,2-bis (3-methoxy-carbonyl-2-thioureido) -benzene. Other biologically active materials that can be included in the herbicidal compositions according to the invention or used together with these are plant growth regulators, such as maleic acid hydrazide, 2,2-dimethylhydrazide of succinic acid and (2-chloroethyl) -trimethylammonium chloride, and fertilizers containing nitrogen , Potassium and phosphorus and trace elements known to be essential for plant life such as iron, magnesium, zinc, manganese, cobalt and copper.

109817/2227

The following examples serve to further illustrate the invention herbicidal compositions.

Example 30 ■

Wettable powder

1- (5-Bromothia2ol-2-yl) -l, 3-dimethylurea 25 g ethylene oxide-octylenephenol condensate 10 g

finely divided aluminum silicate 65 g

The thiazole derivative is dissolved in about 1 liter of acetone, and this solution is sprayed onto the mixture of the other products in a ribbon mixer and crushed to a suitable fineness. This powder is thiazole derivative in water in an amount of 3 * 5 - 14 g suspended per liter of water and in an amount of 335 liters per hectare to control Chenopodium album, Polygonum lapathifolium, Sinapis arvensis, Stellaria media, Alopecurus myosuroides, Avena fatua and Poa annua are used before or after rising.

One can also make wettable powders that are in the same Way are usable, with the l- (5-BromthiazQl-2-yl) * - l, 3 ~ dimethy! urea with the same amount of 1- (5-chlorothiazol-2-yl) -l-ethyl-3-methy! urea replaced. ·

Example 31 Wettable Powder

The procedure is as in Example 30, except that the 1- (5-bromothiazol-2-yl) -l, 3-dimethylurea by the same amount of 1 ~ (5-bromothiazol-2-yl) -l, 3 * 3-trimethyl urea replaced. This powder is in the same manner as that of Example 30 with the same Results usable.

One can use wettable powders in the same way by adding the l- (5-bromothiazol-2-yr) -l, 3,3-trimethylurea by the same amount of l- (5-chlorothiazol-2-yI) -I-

109817/2227

Replaced ethyl-3-methylurea.

Example 32 Emulsifiable Concentrate

l- (5-bromothiazol-2-yl) -l, 3-dirnethylurea 20 % (weight per volume)

Calcium dodecylbenzenesulfonate 5 % (weight per volume)

Ethylene oxide-nonylphenol condensate 5 % (weight per volume) isophorone 2 volumes)

Xylene 2 volumes) _{1 (χ) volume} ^.

k Dissolve the products in the isophorone-xylene mixture. To the Ve? This concentrate is diluted in water in an amount of 7.5% V / irksubstanz per liter and applies the dilution in an amount of 225 liters per hectare to control Polygonum sp., Brassica sp., Matricaria sp.j Chenopodium sp., Stellaria media, GaIeonsis tetrahite, Chrysanthemum segetum, Lamium purpureum, Poa annua and Alopecurus myosuroides in cultures of potatoes by application after the weeds have risen and before the potatoes have risen.

Similar concentrates which can be used are prepared in the same manner with the same results by using the 1- (5-bromine- ^ thiazol-2-yl) -l, j5-dimethylurea by the same amount V l- (5-chlorothiazol-2-yl) -l, 3,3-trlmethylurea, l- (5-bromothiazol-2-yl) -l-ethyl-3-methylurea, l- (5-chlorothiazol-2-yl) -l-ethyl-3-methylurea, l- (5-bromothiazol-2-yl) -1-ethy1-3,3-dimethylurea, L- (5-iodothiazol-2-yl) -l, 3,3-trimethylurea or l- (5-iodothlazol-2-yl) -l-ethyl-3-methylurea replaced.

Example 33 Powder

1- (5-bromothiazol-2-yl) -l, 3-dimethylurea 50 wt .- ^

Sodium salt of the condensation product

of formaldehyde and naphthalenesulfonic acid 5 wt .- # finely divided synthetic magnesium silicate 45 wt .- ^.

109817/2227

The active substance is dissolved in acetone, the solution is dispersed in Magnesium silicate, evaporates the acetone and sets the sodium salt of the condensate too. The powder is dispersed for use by stirring in water in an amount of 5 g of active substance each Liters and applies the suspension in an amount of 225 liters per hectare to control Amaranthus sp., Chenopodium sp., Polygonum sp., Digitaria sp., Setaria sp. and Bromus sp. before the rise of the Weeds in maize crops and before the latter emerge.

A powder is made in the same way, the corresponding one Gives results by using the l- (5 ~ bromothiazol-2-yl) -l, j5-

dimethylurea with the same amount of l- (5-chlorothiazol-2-yl) -l-ethyl-j5-methylurea replaced.

Example 3 ^ .

concentrate

l- (5-BrQmthiazol-2-yl) -l, 3-dimethylurea 40 wt -.% of condensate of propylene oxide and higher fatty alcohols. 0.5 wt. Of distilled water qs 100 vol. ~ $.

The ingredients are mixed and ground in a ball mill during 12 hours.

For use, this concentrate is diluted with water so that 20 g of active substance are present per liter. One uses this means in an amount of 112 liters per hectare to control Bracharia eruciformis, Cynodon dactylon, Echinochloa crus-galli and Leptochloa filiformis in sugar cane crops before the weeds emerge and before or after the sugar cane emerges.

Analog concentrates can be used in the same way by adding the l- (5-bromothiazol-2-yl) -l, 3-dimethylurea by the same amount of l- (5-bromothiazol-2-yl) -l, 5,5-trimethylurea, 1- (5-chlorothiazol-2-yl) -1,3,3-trimethylurea or l- (5-chlorothiazol-2-yl) -l-ethyl-3-methylurea replaced.

109817/22 27

Example 35 Emulsifiable Concentrate

80

l- (5-chlorothiazol-2-yl) -l, 3-dimethylurea 20 % (weight per volume)

Calcium dodecylbenzenesulfonate 5 % (weight per volume)

Ethylene oxide-nonylphenol condensate 5 % (weight per volume) isophorone 2 volumes)
Xylene 1 volume

) q.s. 100 Vol.-Ji.

The products are dissolved in the isophorone-xylene mixture. For use to the concentrate is diluted in water in an amount of 2.5 g of active substance per liter and applies this dilution in an amount of 450 * 1 per hectare for controlling Amsinckia sp., Amaranthus spp., Polygonum spp., Digitaria sp. and Setarla sp. in bean crops before the weeds and beans emerge.

You can prepare usable concentrates in the same way, by the l- (5-chlorothiazol-2-yl) -1,3-dimethylurea through the same amount of l- (5-chlorothiazol-2-yl) -l, 3,2-trimethylurea, 1- (5-bromothiazol-2-yl) -l-ethyl-3-methylurea, 1- (5-chlorothiazol-2-yl) -l-ethyl-3-methylurea or 1- (5-bromothiazol-2-yl) -1-ethy1-3,3-dimethylurea replaced.

Example 36 P powder

l- (5-chlorothiazol-2-yl) -l-ethyl-3-methylurea 50 wt .- ^ sodium salt of formaldehyde-naphthalenesulfonic acid condensate 5 wt .- %

finely divided synthetic magnesium silicate 45% by weight .

The active substance is dissolved in acetone, the solution is dispersed on the magnesium silicate, the acetone is evaporated and the sodium salt is set of the condensate too. A powder is obtained. For use, this powder is dispersed in water in an amount of 5 μ Active ingredient per liter and applies this dispersion in an amount of 225 liters per hectare to combat Alopecurus myosuroides, Poa annua, Avena fatua, Chenopodium album, Galisoga parviflora,

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Polygonutn aviculare, Spergula arvensis and Veronica sp. in wheat fields before the weeds and wheat emerge.

Example 3 7 Concentrate soluble in water

l_ (5_jodthiazol-2-yl) -l-dimethylurea ₄ 3 20% (Gew.Je vol.) aqueous solution of 50% (weight per volume)
Benzalkoniurabromide qs 100 Vol., - $ «.

The thiazolyl derivative is dissolved in the solution of the benzalkonium bromide. For use, this concentrate is diluted with water in an amount of 2.50 g of active ingredient per liter and this dilution is used in an amount of 450 liters per hectare to combat
Plantago sp., Stellaria media, Veronica sp. and Urtica urens in cultures of black currant bushes using after cbm emergence.

Similar concentrates which can be used can be prepared in the same way by mixing the l- (5-iodothiazol-2-yl) -l, 3-dimethylurea with the same amount of l »(5-bromothiazol-2-yl) -1, 3 * 3-trimethylurea, 1- (5-chlorothiazol-2-yl) -l,; 5,; 5-trimethylurea or 1- (5-chlorothiazol-2-yl) -l-ethyl-5-methylurea.ff
replaced.

Example 38

Emulsifiable concentrate

1- (5-Brornthiazol ~ 2-yl) -1,3,3-trimethyl ~

urea 20 % (weight per volume)

Calcium dodecylbenzene sulfonate 5 ^ (weight per volume)

Ethylene oxide-nonylphenol condensate 5 % (weight per volume)

Isophorone 2 volumes) _n _ _1ΛΛ , _{ΤηΛ α}

* ) qs -100 VoI .- ^,

Xylene 1 volume)

The products are dissolved in the isophorone-xylene mixture and thus a concentrate is obtained. For use, this concentrate is diluted with water in an amount of 7 * 5 g of active substance per liter and
applies this dilution in an amount of 112.5 1 per hectare

109817/2227

sp

Control of Digitaria sp., Echmochloa sp. Eleusine sp., / Euphorbia sp. and Portulaca sp. in peanut crops before the weeds and peanut plants emerge.

Comparable concentrates which can be used are prepared in the same way by adding the l- (5-bromothiazol-2-yl) -l,; 3,; 5-trimethylurea by the same amount of l- (5-chlorothiazol-2-yl) -1,3,3-trimethylurea, 1- (5-bromothiazol-2-yl) -l-ethyl-j5-methyl-urea, 1- (5-chlorothiazol-2-yl) -l-ethyl-3-methyl-urea or Replaced l- (5-bromothlazol-2-yl) -l-ethyl-; 5,3-dimethylurea.

I Example 39

Emulsifiable concentration

l- (5-bromothiazol-2-yl) -l, 3-diethylurea 20 % (weight per volume) ^, S-diiodine - ^ - n-octanoyloxy-benzonitrile 7.2 % (weight per volume)

Mixture of ethers of polyoxyethylene, polyoxyethylene glyceride and alkyl aryl sulfonate

available under the name Atlox 3 ¹ IOJ 5 % (weight per volume)

Mixture of ethers of alkyl-aryl-polyoxyethylene and alkyl aryl sulfonate, commercially available under

the name Atlox 3404 available 5 % (weight per volume)

■ Isophorone 2 volumes} _n ^ _1r . _n , _r , ^

* ; qs 100 VoI .- ^.

Xylene 1 volume)

The products are dissolved in the isophorone-xylene mixture. You get a concentrate. For use, this concentrate is diluted with water in an amount of 9 cnr of concentrate per 1 V / water (which is 1.8 g Thiazolyl derivative and 0.45 g benzonitrile derivative, calculated as 3,5-diiodo-4-hydroxy-benzonitrile, corresponds) and applies this Dilution in an amount of 450 liters per hectare to control Avena fatua, Polygonum sp. Stellaria media and Veronica sp. in potato crops after the weeds have emerged and before the kairtoffei plants emerge.

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Example 4.0-3

Emulsifiable concentrate

l- (5-chlorothiazol-2-yl) ~ 1,3-dimethyl-

urea $ 15 (weight per volume)

2,4-dichloro-phenoxy-acetic acid iso-

octyl ester (2,4-D-iso-octyl ester) 15 % (weight per volume mixture of ether of polyoxyethylene, polyoxyethylene glyceride and alkyl aryl sulfonate, ^

in trade under the name
Atlox 3403 available 5 % (weight per volume)

Mixture of ethers of alkoxy-polyoxyethylene

and alkyl aryl sulfonate

under the name Atlox 34θ4

available 5 % (weight per volume)

Isophorone 2 volumes) _{q # B #} . I ₀₀ VoI .- ^. Xylene 2 volumes)

The 'products are dissolved in the isophorone-xylene mixture. You get a concentrate. For use, this concentrate is diluted with water in an amount of 25 cnP concentrate per liter (which is 3.75 g Thiazolyl derivative and 2.5 g of 2,4-D compound per liter) and applies this dilution in an amount of 450 liters per hectare to control Eleusine sp., Echinochloa sp., Cyperus notundus, Ageratum sp. and Bidens sp. in sugar cane cultures after emergence the weeds on. ·

1098 17/2227

Claims (3)

Claims J Thiazole derivatives with herbicidal action of the general formula N-CO-N in which Xi is a chlorine, bromine or iodine atom, Rj is one Represents methyl or ethyl radical, Rc represents a hydrogen atom or ^ denotes a methyl radical and Rg is a methyl radical or, if R ^ and Rr each represent a methyl radical, also an ethyl or n-Propyl radical means, as well as their addition salts with acids. 2. Process for the preparation of the compounds according to claim 1, characterized in that one a compound of the general formula NR ₁ N-CO-N Rr in which R ^, R ₁ - and Rg have the meanings given above, subjecting to a bromination, chlorination or iodination reaction or if Rt- denotes a hydrogen atom and Rg denotes a methyl radical .represents methyl isocyanate with a compound of the general formula 109817/2227 -NH in which R ^ has the meaning given above and Z is a bromine, Means chlorine or iodine atom, converts or a compound of the general formula N - C0 ₂ - in which L and Z have the meanings given above and R.p is an alkyl radical with 1-6 carbon atoms or an aryl radical means with an amine of the general formula H NR ₅ R ₆ in which Rp- and R / - have the meanings given above or a compound of the general formula ■ Ri N - CO-X in which Z and R ^ have the meanings given above and X ₇ denotes a chlorine or bromine atom, with an amine of the general formula HNR ₅ R ₆ in which Rp- and R _{6 have} the meanings given above, converts or if R, - denotes a methyl radical, a compound of the general formula 109817/22 2 7 -N R. NH in which Rj, and Z have the meanings given above, with a compound of the general formula - CO in the X, and
sets or have the meanings given above to a compound of the general formula R ₁ ■ 4 NH in which Z and Ru have the meanings given above, with a compound -N-CO- N " in which Rp- and R ^ have the meanings given above or a compound of the general formula N-CS-N ^R 6 reacts with a lead or mercury salt or if Rc denotes a methyl radical, a compound of the general formula 103817/2227 -N N-CO-NHCH with a compound of the general formula in which Rg has the meaning given above and T is a represents reactive ester radical, converts or if Rp- is a methyl radical, a compound of the general formula Z- -N -N-CO - NH R4, in the Z, pnd Rg have the meanings given above, with a compound of the general formula CH ₃ T in which T has the meaning given above, converts or if R ^, R ₁ - and Rg each represent a methyl radical, a compound of the general formula NH-CO-NH R _r where Z and R ^ have the meanings given above, with a compound of the general formula in which T has the meaning given above, converts or if R ^ and .R ₅ each represent a methyl radical, a compound of the general formula 109817/2227 NH-CO-NH where Z and R6 have the meanings given above, with a compound of the formula in which T has the abovementioned meaning, are reacted. " 3. Concentrated or ready-to-use herbicidal compositions, characterized in that they contain at least one compound according to Claim 1 as active substance. 109817/2227