DE1934809A1 - New hydrazone-N-dithiocarboxylic acid esters and process for making the same - Google Patents

Description

EGYESULT GYOGYSZER ES TAPSZERGYAR in Budape *, Hungary

iiEÜE HYDRAZON-N-DITHlOCJLRBONSAUHE-ESifER UOT TOH MANUFACTURING THE SAME

IN η ErTiMuKf * relates to novel hydrazone 5 [-aitiiiOcäf * Boue '· eäure ester UOwIe ₁ yhainnaaeutlsche preparations, this ITER, the "bonds included _s also ■" Terfahx "η for the production DERS elber? _a . * - ". ■ '.;■." ■ .-. "-: ;;

The new compounds according to the invention have bak- ^ terlcläe, anlhelmintische and viro-s-tat is ehe. ■■ Effect. ',,' ■ - V.

ϊί «are- ereifca some connections with similar; ■ chein.lohen structure known from vJiPrakt ".Ghem" ^ 2 * 59/1916 / " Ζ .. Chem, Soc. 1952,.-29-529 ■. .Sohweia «Pat," Mr. 133.25? - QiXn-

9 0 988 5/1759

1953t 4086 / a). However, the known substances have none therapeutic effect, or is this much less than that of the compounds of the present application.

Compounds of the present application can be characterized by the following formula »

Hi ' ^: - ■■ ■ ..- ■■■

C = H-JIH-CSS-R ³ U)

in which

R waters fabric, an amino optionally substituted by alkoxy "carboxy, carboxylate, carbalkoxy, or amino, alkylamino _r Bialkylaroino and Trialky! ^ Groups .bzw.durch the pharmazeuttes) compatible acidic Addltionsaalze substituted straight or branched alkyl ,, alkenyl * Arälkyl- and ar alkenyl

ν group; an optionally mono- or polysubstituted phenyl wherein the Substitusnien same or different sini undzwar halogen, alkyl, AIkOSy ₉ acyl, hydroxy, carboxy, carboxylate, or SuIfonsäure. Garbalkoxy mean an optionally mono- or polysisbstituierte heterocyclic group such as pyridyl, Xndolyl, quinolyl ₉ thienyl or furyl ,; where the substituents are the same or different and are halogen, alkyl, alkoxy, acyl, hydroxy, carboxy, carboxylate, sulfonic acid or carbalkoxy and

ΈΓ for hydrogen; an optionally substituted straight or branched alkyl and aralkyl group given in accordance with the definition of R ^{1 according to & S, a carboxy or carboxylate}

Group stands - ν ^:

1 2
Furthermore, R and B with the carbon atom to which they are bonded can form a mono- or polycyclic ring containing at least one carbonyl group in which the oxygen atom of the carbonyl group is replaced by a ³ H-IJH-GSS- ^ R Best can be * that of the connection dey Pormel * . .; > ■,

H ₂ F-NH-CSS-R ³ (III)

_ ₂ _ S09885 / 17B9

BATH ORIGINAL

originates in which R is optionally substituted by halogen Atoms or straight or branched alk ^ groups mono- or polysubstituted straight or branched alkyl, alkenyl or Aralky! group.

The compounds according to the invention can be different Way to be made. According to one method, the oxo compounds of the formula

R ¹ ^ CO-R ² · (II)

or derivatives thereof, which during the reaction in the Compounds of formula II are rearranged - e.g. that corresponding potassium lead sulfite, sodium bisulfite, diacetal, Diaeetat or the geminal Dlhalogenivat -with a Dithiocarbazic acid esters of the formula

. H ₂ N-RH-CSS-R ³ (III)

implemented, advantageously at a temperature of 30 to IQO ⁰ G.

12 3
In the formulas, R, R and R have the above meanings.

Conveniently, no more than an equivalent of the Oro compound used in the reaction. The reaction can without the use of a special solvent but also in the presence of a solvent - e.g. water, straight or twofold alcohol, ether, dioxane, tetrahydrofuran, dimethylformamide, dimethyl sulfoxide, substituted or unsubstituted aliphatic or aromatic hydrocarbons or a mixture of these - are carried out.

Be after a particularly beneficial method the starting oxo and / or dithiocarbazic acid bsters, that are formed during the reaction are not isolated and that Heat mixture is processed further without using one special solvent. In this case, the Solvents in the reaction mixtures are not necessarily miscible be. The reaction can be carried out in a homogeneous or heterogeneous phase, at room temperature or below will. The condensation reaction can be caused by higher temperatures

90 9885/1759

BATH

ratures are promoted; advantageously is carried out between 30 and 100 ⁰ C. Warm methanol, ethanol and isopropanol are advantageously used as solvents; in this case a reaction time of 5 ° "" 60 minutes is sufficient, which depends on the reactivity of the oxo compound. If the reactivity is sufficient, the reaction is carried out with cooling. To complete the condensation reaction, however, the mixture is heated to the boiling point of the alcohol used. This latter process is extremely advantageous from an industrial point of view.

According to another method of the invention, the oxo compounds of the formula

R - CO-H ² (II)

or a derivative thereof, which during the reaction in,. These compounds are transferred - e.g. the potassium bigulfite »sodium bisulfite, diacetal, diacetate, or dad ge--. minale dihalo derivative - with a dithiocarbamine salt of formula

H ₂ N-NH-GSS-Z ■ (IV)

condensed, advantageously in the reaction mixture _f in which one or both 'reagents are formed, and the compounds of the formula thus obtained

C * ir-NH-CSS-Z

are alkylated or aralkylated in known catfish. In in the above formulas, R and R have the above meaning, Z stands for alkali metal »alkaline earth metal, ammonium or Hydrazine cation. The reaction is advantageous in hetero- " generPhase carried out, »alas another procedure the solvent used is water, a straight or branched lower alcohol or a mixture of the same.

909585/1759

χϊ, BAD ORIGINAL

turns, and the reaction at a temperature of 0 to 100 ⁰ O completed. This condensation reaction is carried out at a temperature of 20 to 80 ° C and the alk

or aralkylation at Ό big 50 ⁰ C | which depends on the reactivity of the alkylation amlttoiy.

The compounds of formula 1 can also be nn heard that one hydrazones of the formula

with sodium, potassium, N; ¹ · fcriumnmid or Niitrl.nmli.vdT.id sets in front and the connection not received dor Forin ob

"Ι ^: - ■■■■■■. ■■ '- ■■

^ N-NH-Z _χ . (VIl)

with carbon disulfide umnotivt and dio no οrhnitenon compounds form the formula

are alkylated or aralkylated in bnknrinUr .Wn.lne. In

ohifcon Fnrinn'l hatmn R and K the ubi.Re Bed out un ^, and Fitohh. for Nnit ^ um r.dor KmI Ium. ,; . . ν "-"■,.-'.-.,

f) .i © VopHintiunKinn dnr -gi3 ^ enw? trtigiin ßrfindun / ?; can Harn tuwh no_ h ^ v ^ ntr> .l ^: ] t w. «rjd« ri, daiJ one connections. .. de?

■ · χ * V

90 3885/1759

(Which are prepared according to the above reaction or according to other known methods?) with a chloroithioformic acid ester the formula

■■. Cl-CSS-R ³ (Till)

offset »R ¹ YR, R ^ ³ and Z- have the same meaning here as above. ·

The compounds of the formula I can also be prepared by using the compounds of the formula

C = K-NH-Z ₁ (TU)

Reacts with thiophosgene and the resulting derivatives of the formula

C = N-MH-CS-Gl (II)

with a mercaptide of the formula.

R ³ -SZ • (X) ;

1 2 3
lets react .. R, R, R, Z, and Z have in the formulas

the meaning already given.

The two reaction steps are advantageously carried out without isolating the intermediates.

Compounds of formula I are also by the
Reaction of a hydrazone of the formula, -,. ,, · -..- ■■ ".- ■.

with a dialkyl or a 'diaralkyl trithiocarbonate formula. ".... _; " ... .. _f - ...--; ...-.-, -.-, -,.,. _; , _: ; ■ · ■. ■.; -; .. ■ -

R ⁴ -S-qSS-fl ⁴ (XI)

manufactured,

■ -'- "'->;;. ■ - _: Γ :: ^ .-" - ■ " ⁶ " 90 9885/1759

BADOFtIGINAiI

at a temperature below 150 ° C. In these formulas, H ¹ and R ^{2 have} the meaning given above and H ⁴ stands for a non-eucalyzed alkyl or aralkyl. The reaction is advantageously carried out at a temperature between 60 and 100.degree. It is advisable to use the verbiistang of formula XI in excess ",

Compounds of the formula I and their mixtures, or a combination with other pharmaceutically active and / or syn @ rgetisc £ i acting products can ζω conventional pharmaseutic coffi positions for externals, oral or parenteral® administration can be worked up by the necessary solvents »thinners and others Adding tools. Because these compounds are sensitive to acids are, they are beneficial to inteBtinsolvente.i coated tablets processed.

Bithiocarbazine acid esters of the formula

H ₂ I-KH-CSS-R ³ (III)

Can be prepared by reacting hydrasine hydrate with carbon disulfide in an alcoholic medium, in the presence of kallua hydroxide, ammonia or excess hydrazine hydrate, converting the isolated bithiocarbamic acid so obtained into an ester by breaking down alkylation odor Alkylating agents. (J. Chem. SQc. 119> 1921 p. 7β4 »J. Erakt. Ghem. 2>, 1 ^ 16 p. 59. J- 0rg> Chern. ^ 4, 1954 p. 733, J. former Soc. 1952 p. 2959 · J-Indian Chem. Soc. 3_ · 1926, p. 148, Ü.SP 3,261,8581. This last step is carried out in water or in a mixture of water and alcohol or in alcohol alone The reaction is carried out in a single reactor to which the alkylating or aralkyling agent is added as a solution to the feithiocarb base prepared according to the above method

The potassium salt (J.-Prakt. Chem "^ ₉ 1916, p. 59) ₈

909885/1759

^ Salt (J. Chem. Soc. Ill »1921 ^p . 764) and Hydrassonium salt (J. Org. Chem. ^ 4, 1954» p. 733, Ber.22., 1894, p. 59 »J. Prakt. Che / n. £ 2, 1895, p. 486, Micrpchlm. Acta 1959, p. 481, J. Cbem. Übe. 12, 1, 1922, p. 2543) “the compound of the formula III is known from the literature. We made the sodium sala.

The compounds of the present application show a pronounced bactericidal bacteriostatic _# vlrostatische and anthelmintlache effect. In Table I the minimum inhibitory concentrations are given which the investigation of the tuberculoetate-like activity of the above compounds revealed. The data relate to the internationally known H37-RV strain, which is best suited for testing anti-tuberculosis substances, and to some mutants of the same, which are resistant to isonicotiiic acid hydrazide (IHH), streptomycin (STIl) or p -iniino-alicylaic acid (PAS).

909885/1759

BATH ORIGINAL

4th Minimal Table 1. H37 Rv ^ H37 Rv LfN H37 Rv ■ ". STM reo. PAS rj30. Connect ". H37 Rv 6th 10-25 . IWH res. In T / ml Ln SuIa No. 9 Q.025-O ₉ 05, Inhibition ac on ent rat i on 14th 10-25 Culture medium 10-25 -; 5 ^: V ^ V; - ■; " 16 25-50 10 0, £ 0.5 V - 17th 5 0.5-1 1 V- ■ - ■ -1-5 / V-vv 23 5 5 10-25. ■ .10-25: V 24 10-25 10-25 - "5-10 -5 .Vv V 25th , 0.78-1.56 ■; ; ' . ■ 5-10 , 5-10 V1-5: ' 27 3 * 12-6.25,] V-- 1-5 V. 10-25 ' / 1 ^ 5 '., ";. v' 30th 10-25 5-10; . * - '~ 31 6.25-12.5 -5 ; 5-10 ν; 35 12.5-25 LO 10 10-25 / V 10-25'V V 40 0.05, 0.78-] -10-25 42 0.1-1 44 0.1-5 2-5 P ^: 45 10-25 - ₉ 56 _S 5 ■ _f : 2-5-ν-; v 0.1 _: 0.1 V vv. 48 0.1, 0.12 0.1-1 V -. $ · ...: ■ "- .: : V '-. 5 ^' - V ^{L /} 50 0.78-1.56 5-10 V 10-25 BC vi <i-25 V 53 12.5-25, 50 10-25 V oii OeI:. 54 - 50 o.i V-V 55 0.05-0.1 ^ 0-5O V20 '; 63 0.78-1.56 50. 1-10 1-IQ V-; V 64 0.025-0.05, 1-10 -V- - _ - 66 1 / VVV-; V ^:. " 68 100-200 V- ■ vJ "-ν ^; 0.5-1 ^ v 71 10-25 1-2 1-2 ■ 1-5 V 1 ^ -5-ν VV 73 1 - - ! 1-5, - ■ '■ 100-200 > 20ö 10-25 10-50 10-25 5 ^ -10 V ... V V 1-10 10-25 VO.i-i 0.1-1 / «■■. 0.1-1V 10-25 5-io: 10-25 ■■ '. · 0.1-1 .0.T-I V ) 98 8δ / 1 ^V::; 7; ^5f; "j '; - ^: BADÖWGINAL

Table 1 continued

75 10-50. 50 .10-50 1Ü-5Q 77 25-50 10-25 25-50 10-25 79 1.56-3.12, 2-5 2-5 2-5 80 1-10 10-50 1-10 10-50 86 10-25 5-10 10-25 1-5 91 10-25 5-10 - 5-10 ■. 1- ^ 92 50 10-50 10-50 50-iüO 93 5O-100. 1-10 10-50 1-10 95 100 50 50 20-50 103 10 10 10-20 113 10-50 10-50 10-50 10-50 114 1-5 "■■■. ■ - ■ -" ■■ 126 '10-25: 10-25 10-25 10-25 138 0.5, 10-20 10 . ■■ 10-20 10-20 140 12.5-25 »20-50 20-50 20-50 10-20 142 10-25 10-25 10-25 5-10 148 10-25 / 10-25 10-25- 10-25 154 10-25 10-25 10-25 10 156 ■ 50 20-50 20 ■■ '- .. · ■ - 20-50. 158 . 20th 20th 20th 20 ^: 161 10-25 10-25 10-25 10 --V 164 5-10 5-10 ΙΟ; 5-10

- 10 -

/ ITS9

BATH ORIGINAL

CSS «β · C t - t

t V * 9 9 * β 9 «···

κ «ct · t t «te

As can be seen from the table above, acetophenone derivatives containing aromatic or heterocyclic groups - which have a methyl group as a group - show the best tuberculostatic effect. The effect does not depend on the solubility of water. The toxicity values of these compounds are very advantageous, that is, the intraperitoneal LD ^ ₀₄ values in mice as 68. ^ - 1690 ag / kg ₉ the oral * Φ% _Ο values in guinea pigs 200-2000 mg / kg, while the minimum HöQMuhgskonzentrationswarte at 0.1 or 5 T / el lie ί see table lh

Table 2 shows the results of the bacterlostatic Tests (in vitro) of some new compounds too Find.

In the experiments "those in the following Table 2 / a enumerated Bacterium Stumme used. '

11 -. "■.

909885/1759

Table 2 / a

Nf. dee
Tribal Name of the bacterium Remarks Polymlxin empfli Penicillinase 1 . B. GuIi 6R only on
borrowed Penioillinase SaIm. thy phy nmr 1um P. TJ o ~ ti - "W -'- ' j. away. aonnei resist. C, S, T P # S «Ο» Τ 4th Staph. aureus 53R resist. P, C 5 / 3taph. aureus Duncan P, C. 6th Staph. aureue 1104 > resist. for domestic pathogens
sensitive P. S 7th Staph. aureus tour result Ρ * S, C, T ⁸ · Staph. aureus A. result ^ P, S, C, T 9. Bacillus cereus 569 / H ~ resist. C. 1 · »^ -Siuph ^. ^ Auretts ^ GyT ^ ⁷ "^"" ¹ " ^ "" ^ "^^"" resist. ρ, s, σ. τ J-U. -! - ^ - τ. 11. BaciLlus aubtilis ATGC 6633 resist. Penicillinase 12th Jacillus subtills Τ9Θ resist. P. T 13th B. coli 4R resist 14th Candida albicans resist. resilient 15th Staph. aureus 102 resist. 36. E. Oolt. Olli resist. S = streptomycin
C = chloramine-phenol col 17.- ^ l Bacillus cereus result 18th resist. Pseudomonas pyocyanea 13 19th Sarcina lutea ATCC 9341 20th Abbreviations »resist. »- 'reactive» P - penicillin

T = Terramyoia

- 12 -

9098 85/1759

The compounds listed in Table 2 / b have a pronounced or little μtens noticeable effect against the microorganisms of Table 2 / a. ■ -....

Table 2 / b -

Link; No. de a St amme a

5, 3, 9, 15

6 4,6,9,10,11, 12, T i _s: 15,17 14 - I ^ "

18 4, 6, 9, 10, 11, 12, 13, 15

27 15 ^v J '■■■■ .;'

28 3

29 17. ■ ■

30 2, 4, 5, 6 ^ J, 9, 11, 15V 16

35 4, 6, 9, 10, 11, 12, 13, 15- ™ -— = ^^

45 15, - '

53 4, 5, 6,7., Π, 15, 16 / '-.

54 2, 3, 4, 5, 6, 7, 9, 11, 15, / 16, 20

63 2, 4, 6, 9, 10, 11 ,, 12, - "- 14i 15 ..., '\

104 9, 15 '■■' "■

116 7, a, 15, 20 ·; ". .-, ■ '' ._ · ■■" _'_ ■■ ";

119 '4.9, 13.4 15. ^ ^ ~

3, 5, -6, 7, 8, 10, 15 * 16, 20 ";

121 4, 6, 9, 10, 11, 12, 13, ·:. "- ■".,. ". '

4, 9, 10, 12, 13, 1 &

123 15 x; ■. ■ - ". '. ■■■." ■ _.._

134 2 _? 3, 4 _S 6.9, 1O ₉ 11, 12 _r 13, 14, 15, 17, 19

137 2 _S 4 _S 6, 9, 10, 11, 12, 13/14, 15 * 17 »'"' 19 '

20th

2, 4, 6, -9.,. 11, 13, 15

161 4,? * 11 _} 12, 13, 15, 17 '

4, 6, 9, IQ, 11, 12, 13, 15 '

170 9, 10 ₉ 12, 13, 15 .. · '■ -. : 181 4 _S 6, 9, 10, 11, 12, 13, 15

- "■■■ v 90 9 885 /

Dan quantitative impact aspects of some
ca and notcher compounds «which are most effective in the
runs of the above antiiaicrobial pores

in Tables 3 / a and 3 / to below.

fabeile 3 / a

No. * des Peni Strepto- Chloram Terra Connections No. 18- 30 3 5 0 Tribal cillin rajcin phenicol aiyciti fe _ 0 0 0 1 0 0 0 0 0 . 0 50 0 2 8th _? x 10 * 10 0 0 0 5 3 0 2 ^X 2 10 0 10 0.05 - 4th 16 0 0 5 - o, 5 5 % 0 0.5 20th - - 0 0.5 ■ -. 6th .0 0.5 JO 2 5 - 0.5 7th ■■ 16 * 0.5 0 20th - - - - LfN θ 16 ^Χ 2 10 * 20th - 10 0.05 ' 5 la 2 1 0 10 0 -. - 20th 10 0 0 0 0 10 20th 0..5. 5 Ύΐ "\ 0 0.5 0 20th 5 20th 5 12th 16 0.5 20th IO ³¹ 10 -. 0; 13th 0 0 10 10 5 0 0 5 14th 0 2 10 * IO 0 10 0 - ■ - .. - 15th 0 - 0 0 0 5 - '"■■■ o, -5 ^fc .- 0 16; 16 * 0.5 0 20th - 20th 0 - - 17 ■ 0 jÖ 0 0 20th - '. - -. ■ " 0 18th 16 ^s 0.5 20th 0 - 0 0 _ - 19th 0 2 2O ^ 0 0 -20 8th 0.5. ., - IC * "" " 10 -

Comments from Tables 3 / a and 3 / bs

-Not checked
0 no effect '
_for no waxing nail 48 hours inettliation
the minimum doses of effectiveness: are given in | * / ml, with üuenahae of penicillin, where it is given la international units »"

909885/1759

_offlQINAU

OO OO

Sl <&<& S IA 1) Hi _f -4 IA ri H! Approx. SL S Sl i I H H & H H Sl H

f si §

Sl SL. <&. ft I IA I I H H U> H «Λ l & ΙΛ I Ϊ & j

«Ο O OQOO

si Si si hi ι «si ι s η ia w w η ta η

ru

ι rusts, t

«Ι

OO O OO Ο

m ι cm ι i οι si (M «& tu m Iu ι n ι« ι

ON

MMOO O O

η η ηι η ι οι e phi

IA ιαΊαμ ia

H »Μ · · O '· 1 I rH O rH OOHOI

INI

Si SI H I Sl i § (M

ta «&

IA IA SA YES IA IA

ι ο * ι ι o o o o o

ft ft ft ft ft

ο ι ο ι ο ι ο γ ft ι o ft ι ι ι ι i.i. »

O OO

cH β ISL I I H r4

if \ & US > ©. S.

i »

Hi i <Sl t SL I

Yes

, ^M ft

«M

ta, ft ι ία ι e ia u \ * ft \ «a ia« m on ι d ia <ä ι

IA

ft ft IA SA O O O O

ft ft O O

O O O O I OI O 1 IA O

O SL t SL

»-J pH r-S ieoO> H H CM

! 4809

- 15 - 909885/1759

BAD OFWGlWAt-

The antiraicrobal spectrum shows that the new compounds of the formula I _{1 are} mainly effective against grarapaitlve bacteria. Alphatic oxo compounds already show a significant bacterostatic effect, but the presence of a heterocyclic group is also desirable in terms of effectiveness. If one compares the methyl, benzyl and p-chlorobenzyl esters, it turns out that the methyl and the p- Chloro-benzyl esters are more effective than the corresponding benzyl esters. In this area are -

with a few exceptions - such compounds of formula I the

1 2

most effective, in which R and / or R is an aromatic radical or a pyridine group and H is methyl, as well as compounds of the formula I _{9 derived} from the furan, thiophene, indole derivatives of the formula II, or from a salicylaldehyde » where R is a p-chloro-benzyl group.

The exact concentration of effects of the substances could can only be determined in the case of the water-soluble compounds. The "screening test" of the water-soluble compounds was carried out according to Tamm's known method (survivors Ghorionallanteis membrane tissue, from incubated KÜckeneinbrloa taken). The numbers in brackets indicate the difference between the infection factors of the virus strains and the control units, expressed in logarithmic units.

-16 -

90 9 885/1759

BATH ORIGINAL

Table 4

Connection Inhibition of haemagglutinant factor, in #

^Nr * Influence A-2 / Sing Virus strain Influenza AO / M

Virus strain

100

/ Ug / ml. 1000 / Ug / ml 100 v

9. (1,250) 100; .: JO :: \ ','. : -

25 44 - ';; - Λ:

42 27— ■ -.- "" - "

131 100 '- ■■:

136 0. · ■■■■ 100th; ; -

145 0; -; ■■■ -; ■ -:. '; - .: \ -: V "

151 .-. 100 (2.875) - V.

164 (2.875) 100 93 '■■ ":,'

The results of the anthelrainti see "Screening... Te3ta" of the aqueous compounds of general formula I show that they are about an order of magnitude more effective than the well-known fiperazine adipates and about two orders of magnitude less effective than that l- ( fb -Diethylamino-äthyl-amlnoj ^ -inethyHhiazant.hon. '

: Table 5. ".. _; ^: '■' - '".

Connection Enchytraeus alb. Tubifex riv.

No ' -

Minimum anthelmintiacne concentration ^ in mg

ή: '- ■■ "

62.5-125 31- -. ■ " IGOO

1000

■ 7 '" 62.5-125 9 125-250 25th 62.5-125 42 125 58 125 94 5000 Miracil D ^v 1.55 -.,; ■ Piperascat 1000

■ * a β

• Β *

• · ■

• · Λ *

The n ^ n-jn compounds of formula I are not only therapeutically applicable, as indicated above, but are also used world-wide in practice; "They can be used, for example, as chemotherapeutic agents, rubber vulcanizing agents, additives in the manufacture of plastics or Synthetic fibers:

^ are used; some prove to be insecticidal, fungicidal, phytocidal, antioxidant or stabilizing agents in the petroleum industry, as intermediates in the chemical industry, as analytical reagents, etc. The invention is explained in more detail by means of the following examples, not as a restriction to the examples to be included. The following examples describe methods for making esters

'of the dithiocarbazic acid of the formula III (Examples 1-13) »see above such as production methods of the new compounds of formula I (methods A-AU). .

' Example 1":

Dithiocarbazic acid methyl ester

ν 100 g (2 mol) of pure hydrazine hydrate are a mixture of 300 ml of ethanol, 175.5 g (2.1 mol) of potassium chloride and 175 - added water. Become 160 g (128 ml, 2.1 moles) of carbon disulfide added drop by drop to the reaction mixture, which is then stirred for 1 hour and cooled in a salty ice water bath. The mixture becomes another Stirred for hour under cooling and 265 g (200 ml, 2.1 mol)

. Dim thyulfate and 500 ml of water were added drop by drop over a period of 30 minutes. Meanwhile, the crystalline methyl ester begins to precipitate. It is immediately filtered and washed with 2 × 100 ml of ice water, 100 ml of 48% by weight of cold water, aqueous ethanol and washed with 100 ml of carbon tetrachloride after vigorous dust removal. The substance is air-dried to constant weight; one receives 170-185 g of a bright yellow product. Yield $ 69-76. F. 65-8O ⁰ G. The unpurified substance has an irritating smell. The crude product can be made from three times the amount of bees oil (yield 82 % of theory, F. 78-82 ° G) or from a three-fold amount of

- Ί A - XO

9098 85/1759

ORIGlNAL BATHROOM

ff «t t ·« »» * C

t β crv4t

· Β r «9« ti

48 wt. # 1geii aqueous ethanol (yield * 7Oj6 ά.Th, P. 80-82 ⁰ C) are recrystallized with equilateral decolorization with charcoal. Colorless crystal grains are obtained which, after one month, turn brown or purple due to the metallic impurities. In order to remove the impurities, it was recrystallized with special solvents so that the metal complexes dissolve. According to this process, the crude product is dissolved in a three-fold amount of carbon tetrachloride «methanol (3: 1) mixture with rapid heating; at the same time, the solution is decolorized with 5% by weight of charcoal. When cooling, small® crystals separate * which, if left in the refrigerator for 1 day, grow into large, colorless crystal grains «. The crystal suspension - is filtered9 washed with 2 x 50 ml carbon tetrachloride, - dried in the air, protected from dust and metal contamination. Yields 137-140 g. The mother liquor is concentrated to half, cooled and kept in the refrigerator over Stacht. The second generation which separates out is filtered and the crystals are washed with 2 × 20 ml. Teträchlo: drohl @ nstoff. The melting point and purity of the substance thus obtained correspond to those of the first generation. Yield 13-15 * 5 g

Gesaiiitausbeutei 150-156 * 5 g (61% * 5-64 d _e Th.). Ps 81-82 ° C degree of purity (based on S & or on the conductometric filtration results as $ 9.2-99.8 -.%.

Pure hydrain hydrate can be obtained through a corresponding Amount of an aqueous Hydrasioliy & rat solution to be replaced j in this case, however, the quantity of water in which the Potash hydroxide is dissolved with the amount of water introduced of the hydrazine hydrates are reduced.

Example 2t

Dlthlocarlsasinsäure-ätfey! -Ester

7 «75 g (6 * 2 ml β 0 _e 102 Moll carbon disulfide are added dropwise in one hour to a mixture of 5 g (0.1 mol) of pure Bydraalnhyto & ta 6 g (0 _o 107 mol) of potassium hydroxide, 6 ml of water and 2'5. ® 1 IthaBol _s while stirring and up to the water bath

909885/1759

BAD ORlGJHAL

t. I · ' ¹

<1 t I

It

cooling added. 14.8 g (7.7 ml, 0.095 mol) of ethyl iodide or 14.65 g (12.5 g, 0.095 mol) of diethyl sulphate are added to the two-phase reaction within 30 minutes The equipment is warmed to 25 ° C. in 30 minutes, then cooled to 10 ° C., 50 ml of water are added and the yellowish oil which separates out is isolated. The crude ethyl ester obtained has to be worked up immediately, since on standing the substance decomposes with elimination of ethyl mercaptan. The crude kann'höchstens'1 day without stabilization left etehen "ground, or need to keep moving over anhydrous sodium sulfate w th. After" another method, the crude ethyl ester is not precipitated with water, aondern is the oxo compound of the for τι- el II added immediately to the alcohol solution.

Example 3; .

AlTyl dithiocarbazinoate

The procedure is as in Example 2, with the difference that instead of ethyl iodide, 7.26 g (7.73 ml, 0.095 mol) of allyl chloride or an equivalent amount of allyl bromide is used. The mixture is ^{heated to 40 0} O for 1 hour, the allyl ester partially separating out . The oxo compound is added to the mixture thus obtained because the yellow oil formed decomposes on standing. ⁰
Example 4:

Dithiobarbaziric acid butyl - 08ter

Proceed as in Example 3, with the difference, '■' -. that instead of allyl chloride, 13 g (10.2 ml, 0.095 mol) of n-butyl bromide are used. The ester can by precipitation fflit a large amount of water to be isolated, but the reaction mixture is added vorzugeweiöe the Oxoyerblndung § without Zwischejq ^ roduct isolate. It is even more advantageous to use n-butyl iodide in the above process.

Example 5s

Dlthiocarbazine acid n-octyl ether

Proceed as in Example 3, with the difference that instead of allyl chloride, 17.4 g (0.096 mol) of n-octyl bromide

- '-' ■■ - ■ ■ ■ '' - ■ '■ ' .- 20 - ^:

909885/1759 _@AD original

is used. The mixture is heated to 40 ⁰ C, and then abgekühlt.Der Octyleater separates in an oily form, and crystallized on standing. The crystals are filtered and dried. The crude product can be recrystallized from a 3.5-fold carbon tetrachloride: ethanol solvent mixture (2t 1). White, shimmering "-" lamellas are obtained, F .: 78-79 ⁰ G.

Analysis (CgH ^ NgS ^ SO ^ l) - -

Calculated: I 12.71% S 29'.1O 36 '/. Found: N "12.38% S 29.02 ^ ■,

Example 6

Dithiocarbazole acid lauryl ester

Proceed according to example 5 "with the difference, that instead of n-ootyl bromide, 22.4 g (0.09 mol) of n-dodecyl bromide is used. The crude product is precipitated with 250 ml of water

I!

and recrystallized from a carbon tetrachloride (2: 1) mixture of ethanol. White, shimmering lamellae are obtained from 92-93 ° C.
Analysis (C ₁₃ H ₂₈ N ₂ S ₂ = 276.51).
Calculated; Ϊ ". 10.13% b. -23-. 19.5t 'found ι N 9.74% S 23.31%

Example 7 ^. '. - /

Cetyl dithiocarbazate _; ,

The procedure is as in Example 6, with the difference that instead of n-octyl bromide, 27.4 g (O.O9 Itöl). Getylbromid used wirdV-result is a waxy substance "which, after repeated recrystallizing from ethanol at 86-88 ⁰ G melts. ,. ".". "

Yield? 64 % of the total ''

Analysis (C ₁ OH ₃₆ N ₂ S ₂ = * 332.62)
Calculated! N 8.42% S 19.28% Foundj N 8A3% S 19 * 42% -, '

Example $ 8. ,

Dithiocarbazic acid benzyl ester

78 g (62.5 ml, 1.025 mol) carbon disulfide will be

: 9D9885 / 17 59

drop by drop in one hour to the mixture of 50 g (1 mol) of pure hydrazine hydrate, 60 g of (7) mol) potassium hydroxide, 80 ml calf and 250 ml ethanol while stirring and cooling in an egg bath. Part off. 126.5 g (114.5 ml «1 mol) of benzyl chloride are added dropwise to the reaction mixture obtained. The excretion of the 3 benzyl ester begins during the admixture. The temperature of the bath is gradually increased to 35 ° C. over the course of one hour, then the reaction mixture is cooled with an egg-water system, while 150 ml of water are added over the course of 15 minutes. The mixture is filtered and the light yellow crystal needles are washed with 2 × 100 ml of 50% ethanol. Is Daa weight of the crude product obtained, 140.5 g of dry (71 # of theory), m.p .: 120-126 ⁰ C. After Umrkistallisieren of a 7-fold amount of benzene yon in the presence of activated carbon, the yield is 74%, d .Th. and SV: 129-131 ° G. After repeated recrystallization from a 4-fold amount of ^ ethanol * F .: 129-13O ⁰ G, yield 89 ^. White, loae Kriatalle are preserved.

: Example 9 ^:;

• ßithiocarbazinaäure-p-chlorobenzyl-eater

The procedure is as in Example 8 with the difference that 1 mol of p-chlorobenzyl chloride is used instead of benzyl chloride. The crude product is obtained with a yield of 80% of theory. obtained, F.ι 125-130 ° C. The substance is recrystallized from a carbon tetrachloride / ethanol mixture (1: 1) or from ethanol or methanol in the presence of activated charcoal. White, slightly light-sensitive needles are obtained, F, ₅ 135-137 ⁰ C. - '/
Analysis (C ₈ H ₉ OlUT ₂ S ₂ = 232.76)

Calculated: Έ 12.03 % 3 27.55 % Cl Vy JO% Found «» 11.85% S 27 * 72% Cl 15.25 J,

Example 10,

Dithiocarbazlic acid p ^ ethylbenzyl-eater

. V '' ■■; ■ ". ■■■". ■ · - - 22 - -.

909885/1759

BAD ORJGIMÄi

«· Β * a * - te ν

# 9 t · -t

The procedure is as in "Example 8, with the Unt-ornchi ed" that instead of benzyl chloride, L mol of p-ethylbenzyl bromide is used. The raw enter is obtained with a yield of 60 # d.Th. obtain. The substance is coated with a 9-fold carbon tetrachloride-alcohol solvent. On earth weifls, ο jollowing lamellae preserved P,: 142-144 ° 0. _f

_??? Analysis (C _{1 (y} f ₁₄ I S ₂ * 2PG.3) Calculated: I 12 "8%> 3 28.33 *

(iefundenr If ί '<?. 60 ί S --28. ^ 8 *

Example II

Dithiocarba? .InaäurR p-Ieoprop.vl ~ benz, vl-OHter The procedure is as in Example 8 with the difference that instead of benzyl chloride, 1 mole of p-laoproyyl-benzyl bromide is used. The raw eater is obtained with a yield of 63 % of theory. The substance is crystallized from pure triple carbon tetrachloride ethanol. The white crystal powder obtained melts at IJb-137.5 ° C.
Analysis (C ₁₁ H ₁₆ I ₂ S ₂ »240.40)
Calculated*. 1 11 .i> 5 * S 26.68%

Found: 1 11.50 3 & S 26.81 *.

■ Example 12s ■ -. -

DithiocaroazinsMure pn- ^ butyl-benzyl -enter The procedure is as in Example 8, with the difference that 1 mol of pn-butyl-benzyl bromide is used instead of BeiiEylchlorids , crude ester is used with a yield of 74% of theory. obtain. The Sultan is a ert au <* 4.5 times TetrachlorkohlenstoffsAthanol Lb'eung ^ mittelgemiach (2s 1) urakristall lsi. · The resulting "white, shimmering fins melt at 130-132 ⁰ C ₀
Analysis iG ₁₂ ^H ia ^ll 2 ^S 2 ⁼

Calculates ι R. 11th .01 * S. 25th .21 * Found! Έ 11th .10 * S. 25th .18 *

909885/1759

BATH ORIGINAL

ti ι 1

Example] 3;

^ ithiocarbazinaäure crfHÄethylbenzyl-eöter ■
The procedure is as in Example 8, with the difference that instead of benzyl chloride, 1 mol of C- | methylbenzyl chloride
is used. The raw eater is veined with a 'yield. 58 % of the total received. The substance only comes from one. Carbon tetrachloride: Ethanol solution mixture / (2j1), sodami from
Umkrigtalliaiert ethanol. The white shimmering fine needles obtained melt at 135> -137 ° C.
Analysis (CgH ₁₂ N _? S ₂ = 212.34)
Calculated: N 13.19. * S 30.20 #

Found: H 13.2O ^ S 30.06 ^ 6

0 9885/17 59

8AD ORIGINAL

' 193Λ809

Procedural method
Procedure A

A mixture of 13.6 g fO.l mol) furfural acetone, 12.2 g (O.l mol) dithiocarbazinaic acid methyl ester (prepared according to Example 1) and 5p ml of ethanol is 5 minutes refluxed. Shimmering shades shed while cooling brick-red lamellae from the light red solution. The mixture is chilled with bis for a few hours, then

Il

filtered, and the crystals washed with 20 ml of ethanol. Yield; 20.6 g (86 % of theory), mp .: 136-138 ° C. The furfuralacetone hydrazone-N-dithiocarboxylic acid methyl ester (compound no. 44) can be prepared from a 25-fold amount of methanol with a yield of 70 % of theory, and a 10-fold amount of ethanol with a yield of 90 '# of theory, and from a 11-fold amount of isopropanol.mifc a yield of 90 % of theory be re-kriatallisiert. The purified product melts at 138-139 ⁰ O.

Analyae iw = 240.34; the product was crystallized from methanol) '

Calculated! N 11.66 $ S, 26.68% Found K 11.82 % ' S 26 * 62 %

Procedure B

A mixture of 12 g (0.1 mol) of acetophenone, 12.2 g (0.1 mol) of dithiocarbazinaic acid inethyl ester and 100 ml of methanol is refluxed for 10 minutes. On cooling, acetophenonhydrazone-N-dithiocarboxylic acid methyl-eater (compound no. 53) excretes from the room in the form of thick, pale yellow, shimmering needles. Yield? 93 #, · Fs 148-150 C. The crude product can be recrystallized from a 15-fold amount of ethanol with a yield of 84 % . F .: 149-150.5 ° E.
* Analysis (M = 225.35)

Calculated {IT 12.49 H> S. 28.58 $ Foundj 3J 12.59 ^ S 28.50 $ ·

-25 - = ■■■: ■■ .. ■, - ;. -.- ·;

9 0 9 8 8 5/17 5 9 BAD ORIGINAL

Procedure C

A mixture of 26 g (0.1 mole) laurophenone, 13.4 g

Il

(OiIl mol) DithiocarbazinBäure-raethyl-ester and 100 ml ethanol is heated for 5 minutes at a temperature of ⁰ C 6Q, added 5 ml of water, and dag mixture overnight in a refrigerator maintained. The white, loose waxy precipitate obtained has a dry weight of 26.2 g (72 #.) And melts at 58-62 ° C. Laurophenone hydrazone N-dithiocarboxylic acid methyl ester (compound no. 195) melts at 62-63 ° C. after recrystallization from J times the amount of ethanol.

Analysis (M = 364.62) Calculated! S .17.58 % Found: 3 17.40 ^

Method D * -

A mixture of 12 g (0.1 mol) of acetophenone, 13.6 g (0.1 mol) of ßithiocarbazinsäure-äthyl-eater just prepared according to Example 2) and 100 ml of 75% aqueous Ithanpl are boiled in a wafiaerbacl of 80 ⁰ C for 10 minutes under reflux . On cooling, a light yellow crystal powder separates out, which is filtered, washed with 25 ml of ice-cold ethanol and dried. 20.45 g (86%) of acetophenone hydrazone N-dithiocarboxylic acid ethyl ester are obtained. M.p .: 129-130 ⁰ C. The Erodukt '^ compound no. 73) achmilzt at 129 .5-131 ⁰ C after recrystallization from a 12-'fachen amount of ethanol. . Γ '

Analysis (M = 238.36)

Calculated »! I 11.75 % S 26.90 ^, found: E 11.9Θ %. S 27 * 00%

Method E

A mixture of 12.1 g (0.1 mol) of 2-acetylpyrldine and 12.2 g (oil mol) of dithiocarbazoleic acid methyl ester and 100 ml of ethanol is refluxed for 10 minutes. On cooling, pale yellow needles separate from the mixture, which are filtered, washed with 2 × 20 ml of ethanol and dried ^{at a temperature of 50 ° C.} 2 ~ acetyl pyridine

90 988 5/17 59

BATH ORIGINAL

I · ■

• t » « β

β 9

; ^: ■■■■ .- Vt ■■ ;. ■■ _v ; ... '.

-hydrazone-N-dithiocarboxylic acid-inethyl-eBter (compound no, '; -30) can be recrystallized from a 3-fold amount of' ethanol with a yield of 82%. The melting point does not increase even after recrystallization.

Analysis (M = 225.34)

Calculated! N 18.65 ■ & S 28.45 * Found: H 18.57 % S 28. %%

Procedure P.

A mixture of 11.4 g (O.M mol) heptanone-2y 12.2 g \ (0.1 mol) dithiocarbazic acid fliethyl ester and 200 ml of ethanol are refluxed for 30 minutes. Eawerden 400 ml of water are added and the mixture is placed in a refrigerator. Heptanone-2-hydrazine-K-dlthiocarboxylic acid -methyl-eeter (compound no. 36) separates in the form of a The oil appears as white crystals within a few hours stiffens. The crystals are filtered and placed in a vacuum desiccator dried over phosphorus pentoxide. Ea - «earth 19 g (87%) of the substance received, F .: 75 ~ 77 ° ö. The melting point rises also after the above-described cases from an ethanol solution not.

Analysis (M = 218.37)

Calculated ι IT 12.83 % S 29.36 * Found! H 12.62 % S -29.07 * "

Procedure G

A mixture of 31.65 g (0.1 mol) of PalmitopheDOö, 33.25 g (0.1 mol) of dithiocarbazine acid cetyl ester - prepared according to Example 7 - and 200 ml of ethanol is refluxed for 1 hour. Upon cooling and rubbing the inner wall of the vessel, a light yellow, loose, waxy product exudes. The crude product is dried over phosphorus pentoxide in a vacuum desiccator. Yield! 54.2 g (86 ^ d.Th.), P.ϊ -63-67 C. Palmitophehon-hydrazone-N-dithiocarboxylic acid-cetyl- ester (compound no. 208) is dissolved in alcohol, and the solution is decolorized with activated charcoal, then the substance is precipitated with water. The purified product melts at 68-70 ⁰ O *

; '909885/17 5 9

"" ■ ". BATH

Analysis (M = 631.14)

Calculated N 4.44% '

Found; N 4.30 '$' method H

A mixture of 26 g (oil mol) of laurophenone, 19.8 g (O ₄ I mol) of benzyl dithiocarbazate (prepared according to Example 8) and 300 ml of ethanol are refluxed for 1 hour. When cooling, almost white, fine needles are excreted. Yield; 27.7 g (63 % of theory) F .: 1O2-1O5 ° C. The laurophenone hydrazone N-dithiocarboxylic acid benzyl ester (Compound No. 206) 'melts at 105-107 ° after recrystallization from a 10-fold amount of ethanol.

Analysis (M = 440.72)

Calculated! N 6.36 # S 14.55 #

Found * H 6.70% , S .14.32 $

Procedure I.

. A mixture of 15.2 g (0.1 mol) of vanillin, 12.2 g (0.1 mol) of methyl dithiocarbazinic acid and 60 ml of methanol is boiled for 30 minutes. During this time the yellow crystals begin to precipitate. The mixture is cooled, filtered, the crystals are washed with 2 × 20 ml of methanol and dried to constant weight. 22.6 g (38.5 #>) vanillin hydrazone K-dithiocarboxylic acid methyl ester (compound no. 47) are obtained, F .: 162-163 ^O C (decomposition), Daa product decomposes at 164.5 ° C Recrystallize from ethanol,

Analysis (M = 256.35) Calculated! S 10.93 # Found; K 10.95 # Procedure J

11., 2 g (0.1 ώοΐ) cycloheptanone are the suepeneion. of 12.2 g (0.1 mol) of dithiocarbazic acid methyl ester in 30 ml abs. Ithanol added. The reaction partly plays out immediately, with little heat development. The condensation is completed by refluxing for 15 minutes.

- 28 -

909885/1759

·.-.-- V BAD ORIGINAL

Upon cooling separates cycloheptanone hydrazone N-dithiocarboneäure-methyl-eeter in the form of colorless needles yield (Compound No. ". 34). 16.5 g (76 · 5%)" F.5 116-118 ⁰ C. The crude product may consist of a 5 ~ times the amount of ethanol in a yield of 82 # d.Th be umkiiatalliaiert P:... 119-120 ⁰ C.

Analysis: (M = 216,376)

Calculated N .12.95 % S 29.63%

Found: F -12.94% S 29.60%

Verfa lead K

A mixture of 1b.3 g (oil mol) of 2,6-diacetyl-olefin, 244 g (0.2 mol) of methyl dithio.carbazinate and 300 ml of ethanol is refluxed for 10 minutes. During this process, 2,6-piacetyl-pyridine-di-hydrazone- ^Nij0l _s N -bis-dithiocarhonBäuro-methyl-ost.er (Compound No. 11.5) precipitates in the form of a yellow crystal powder. The Gemiach is chilled in ice, filtered * the crystals are

Il

washed with 2 χ 30 ml of ethanol and ^{dried at a temperature of 50 0} C to constant weight. Ea 34> 2 g ("92 # d.Th.) of the product are obtained" Ps 191 ⁰ C (decomposition) ". Since the substance is difficult to dissolve, ea can advantageously be purified in the following way: -fold amount of ^{dimethylformamide heated to 80 0} C, the suspension is cooled and filtered and the crystals are washed with ethanol, F .;. 195 ' ⁰ G (erosion) *

Analyaei (I = 371.05) *

Calculated: N 18 * 85 * S 34.52 ^

Found: N 18.70 % S 34.60%

Method L ',

12.2 g (0.1 mol) Dithiocarbazinaäure-methyl ester are dissolved in 200 ml, heated to 50 ⁰ C Ithanol and 12.2 g (0.1 mol) Salicylaidehyd "added The KondeesationsreaktloM occurs immediately ,, evolution of heat. The mixture is boiled for 5 minutes and then cooled in egg water. The rich precipitate of colorless, fine needles is filtered and

- 29 - "" ■■ "'■■■" ■'

08 ^ 057 17 59

raifc 2 × 20 ml of ethanol. - Yield * 19.85 g (88 ', Ό d.Th.h P-. Ι 197 ° C (-decomposition), salicylaldehyde-hydra2on-! R- -dithiocarbongäur-niethyl-eater (compound no. 27) "can from a 30 times ₍ _, e \ ron ethanol with a yield of 70 <# of theory can be converted into iriatallia. F .: 199 ⁰ C (decomposition K.

Analysis (M = 226.3J) .

Calculated: N "12.J8 ί S 28.33 # Found: N 12.50 * S 28.35 #

SaI iny IALD eh.yd can III and IV isolated from the crude product containing w by means of the oxo compounds of the formula as? was obtained using the Reimer * -Tlemann reaction. .

Method M -.

A mixture of 13.4 g (oil mol) of o-phthalaldehyde, 24 Λ g (0.2 mol) of JJi thiocarbazinnäure-tnethy 1-eater and 100 ml of ethanol is refluxed for 10 minutes. The o-phthalaldehyde-dihydrazone-NiN'-bia-dithiocarboxylic acid-methyl-eBter (compound no. 84) separates in part during the boiling process. The mixture is cooled, filtered, the crystals with. washed with a small amount of ethanol and dried. Is yellow needles obtained »yield? 30 g {88 % of theory) »P.-r 140 ⁰ C (decomposition). The crude product can be purified advantageously as follows: The substance is treated for 30 minutes with a 3-fold amount of hot ethanol, the Geraiscii filtered in the hot state _s and the crystals dried. The purified material melts at 146 ° G (Zersetaiiiig).

Ansly.se (M = 342.54)

Calculated! H 16.36 ^ S 37.44 # Found N 16.3O ^ S '37.37 * ■■ method Ή .

A mixture of 10 g (0.1 mol) acetylacetone 9 25.6 g (0.21 mol) dithlocarbaainaiure fliethyl ester and 100 μl abs. ithanol is boiled under reflux for 30 minutes. The yellow solution obtained has a light, asm ^

BATH ORIGINAL

I (f

similar smell. iJie Löoung is kept in a refrigerator. i'icetylAceton-dihydrazon-H.N'-bia-dithiocarbonetture -niethyl-ester (compound no. j5) separates out in the form of light yellow, transparent granules from »yield of 23.35 g (? 6.5 % of theory P .: 1 M) -l'i5 ^q C. After Umkriatallleieren from ethanol fa ^ t colorless crystal grains are obtained, Fi

Analysis (M = JOö. ^ 2)

Calculates % N 18.1b % S '"41.5b $

Found; R 17.θ J I 3 41.5-3 *

Procedure P

A mixture of 15.6 g (0.1 mol) of furfural _{acetone B} 19.8 g (0.1 mol) of iHthiocarbazic acid benzyl ester and 15 ml of ethanol is boiled for 1.5 minutes under high flow. After cooling in the refrigerator, light red lamellae separate from the red solution. The crystals are filtered, washed with 2 × 20 ml of methanol and dried at a temperature of ^ OC. 30.2 g (96 -jb d.Th .l of the crude product is obtained, mp 8106-109 ° C. The furfural-acetone-hydrasson-K-dithiocarboxylic acid benzyl-oster (compound Sr. 1 ^ 4) is purified in the following way? The crude product is finely ground, in 100 ml heißera 80-jb aqueous ethanol, the suspension is cooled and filtered. the purified material auhmilgt at 108-110 ⁰ C. Umkiiatallisieren of a 3-faofaen amount of ethanol does not increase the Schiselspunkt.

Analysis (M »316.53) '

Calculated H 8.85 * S 20.26 $ Found! H 8.98 % S 20.40% Yerfahr en Q

40 ml of concentrated hydrochloric acid and 20 ml of Waneer & 6Γ solution of 16.6 g (0.1 mol) of phenylacetaldehyde-dlmethylaceta € in 300 ml of methanol are added and the resulting mixture is ^{stirred at a temperature of 45-5O 0} C for three hours, then cooled with bis-water and neutralized with a solution of 20 g of sodium hydroxide in 50 ml of water.

- 9 0 9 8 8 5/1759

BATH ORIGINAL

12.2 g _(θ β 1 mole) Dithiocarbazinaäure-methyl ester are added to the ao Löaung obtained immediately, the mixture is heated over 30 minutes to a temperature of 60 ⁰ C, after which 500 ml of water are added. The mixture is cooled, the yellow precipitate is filtered off, washed with water and dried. 13 g (58 % of theory) of the crude product are obtained, P .: 142 ^° C. (decomposition). The compound obtained is dissolved in ethanol and precipitated with water. The Phenylaeetalaldehyd hydrazone N-dithiocarbonic acid-methyl ester (compound no. 52) separates as an amorphous yellow Pui-ver, F.-s 150 ⁰ C (decomposition) .When admixing the compound to the method D is not prepared according to Schmotpunktdepreaeion observed.

Analysis (M = 224.35)

Calculated? N 12.49 % S 28.56% «

Found N 12.40% S 28.31%

Procedure R

A mixture of 12.2 g (0.1 mol) of salicy! Aldehyde 23.25 g (0.1 mol) of p-chlorobenzyl dithiocarbasinate (prepared according to Example 9) and 300 ml of ethanol is refluxed for minutes. The device is cooled with ice, and the precipitated, light yellow, loose needles are filtered, washed with 2 × 50 ml of ethanol and dried. Yield! 32 g (95-5% of theory), Fs 189-191 ⁰ C. Salicylaldehydnydrazon-N-dithicarbonsäure-p-chloro-benzyl ester · (compound no. 134) uffikristallisiert from ethanol in the presence of activated carbon. The white needles obtained melt at 190-192 ⁰ C.

Analysis (M = 336.8?)

Calculated ι N 8.32 % S 19.03 %

Found If 8.13% S 19.19%

Procedure p

A mixture of 11 g (0.1 mol) of 2-furyl methyl ketone, 19.8 g (0.1 mol) of ditniocarbazic acid benzyl ester and 150 ml of ethanol is refluxed for 5 minutes.

- 32 - _

909885 / 17S9

;.;:;> 'BADORIGiNAl.

The mixture is cooled and filtered, the crystals washed with 2 × 20 ml of ethanol. Yield: 26.9 g of T93 % of theory ), F .: 131-I) J ⁰ C. The ^ -Puryl-inethyl-ketone-hydrazün-N-dithio- _ carbono-acid-benzyl-ester (compound; No. L? 2.) Melts at 1'32- 134 ⁰ C, after recrystallization from ethanol. Yellow, fine needles are obtained.

Analysis (M = 290.41)

Calculated: N 9.65 i> "S-2 ^ _.08%,

Found: N 9.50%. '. S- ?? ΛΙ £

Procedure T

2 3.2 g {0.1 mol) DL-10-camphor sulfona acid becomes por ~ tioh-sweiae of the Lcteuru>; of 5/1 g (0.1 mol) Kalj umh.yrirox.yd in 60 ml ethanol are added with stirring and cooling, then 12.2 g (OVI Mo]) dithiocarbazic acid methyl ether are added and the Lb '. <iun _f »· Boiled under reflux for 15 minutes. The mixture is kept in the refrigerator overnight. The precipitated white Kaliuinrvalz is filtered, washed with 2 × 20 ml of ethanol and dried. Then the weight of the received DL ~ * IU -— K ampfe rs u1fönπH11 re —kali um-hydraz οη — Nd it hi ο c arb υ naau re - -methyl-entere f connection no. 94) amounts to .27 .3 g ( ^f / 3 % i "F. ι 290-30O ⁰ C (decomposition). After drying in ethanol, the decomposition point rises to 305 ° C. The connection is good in water soluble.

Analysis (M = '374.60)

Calculated: N 7.48 % S 25.67 % ,

Found: N 7.29% S 25.46%

V er fahr en Jl

A Gemla.ch of 11.6 g (0.1 mol) levulinic acid _s 12.2 g (0.1 mol) diethLocarba ^ irisäure-methyl-eeter ¹ , 300 ml Benael and 7b ml ethanol is heated under reflux for 30 minutes'

and then Gemi "; h to a quarter of a volume .at 50 mm. Hg a / r; f3ongt. On cooling, LEvulinic acid-hydrazone-M-dhlncarbonfjäure-methyl-eBtör (compound no. 10) separates out in a form of white crystals. Prey? 20.1 g (91.5 <$> d ^ h *), Pt l5) -155 ^fJ C (Zorset / ung). The substance is in the mixture

• - 33 -

BADORLGiNAL

Ct

of benzene and abs. Ethanol (4 liters dissolved, the solution with Activated charcoal decolorized, filtered, the piltrate to a fourth] its volume was concentrated and the residue was cooled. the precipitated white crystals melt at 157 ° C (decomposition).

Analysis (M = 2? Q.32).

Calculated: If 12.72 % E 29.11 $ Found s SF L2.57.-j6- S- '24.20%.

Procedure V

A mixture of .16 .8 g (0.1 I.il} oC-iCeto-glutaric acid-mononafcrium aces, 12.2 g (O.l mol) dithiocarbazic acid -methyl-ester and 150 ml 80 & -igea ethanol is 15 minutes refluxed. 100 ml of benzene are added and the solution to half its volume in a vacuum at a Temperature of about 50 ° G, "concentrated. The residue is cooled down, and the excreted csC-keto-glutaric acid-mono- sodium salt hydrazone N-iiithiocarlsonic acid methyl ester (compound Mr. 7) filtered and washed with isopropanol »Das Product has sufficient purity »

25 g (Ol mol) of the -. Connection- # 8 are dissolved in the IiÖsung of 4 g sodium hydroxide or 5.3 g Fatriumcarbonat in 50 ml of water under cooling .. The solution is maintained at a below -20 ⁰ C temperature lying in vacuo evaporated (advantageously by means of freeze drying), the product obtained is pulverized and treated with 2 × 50 ml isopropanol. 22.6 g (83 % of theory ) of the above compound are obtained, Pt 192 ⁰ C (decomposition).

Analysis (M = 272.29)

Calculated: N 10.29 * 3. 23.35% Found N 9.88% S 23.31 % - .

Method 2

.25,2 g (0.1 koi) of DL-p-Nit3? O- ^ -ac et amino- ^ ~ -hydroxy-propiophenone are dissolved in 200 ail heated to 6O ⁰ C * dimethylformamide the mixture, the Löfiung of 12.2 g (0.1 mol) Dithiocarbazlnaaure-inetViyl-enter in 100 ml of ithanol added and the yellow solution obtained with niner

SAD ORlGWAL

Temperature ¹ of 60 ° C. for 30 minutes. The mixture

in the
is decolorized and poured 1 ^ 00 ml of water. The DL-p-NitrooC-acetamino-A-foydrox ^ -propinphenon-hydrazone-N ^ -dithlocai-bonaäure-methyl-eater (compound: No. 114) precipitates as a yellow crystal powder. The Peatsubatanzen be filtered "3 χ 30 ml of water ^ e"aM;. Hen and hei oiner temperature of 40 to ⁰ ^ O ^ C until weight kυη3tanz dried. Yield: 29.85 g (84 d.Th.), F .: l (. ^ -] b8 ° G (decomposition). The crude product is purified as follows: The solid substances are suspended in a small amount of hot ethanol or removed a large amount of ethanol umkr'i3tal 1 ined. In both cases you erhHlt an x-OHES production-t, which is at I68-169 ⁰ C melts ■ iZernetzuni? :) · ßi ^{e n} <> substance obtained has, in accordance with procedures P obtained compound added, no melting point depression on »

Analysis (M β Jh ^ .ΛΑ)

Calculated: K Ib.7 «'>' S 17. * 9 h Found: R lh. ^ J 3 18.08 *

Procedure X. -

Sin -Iead.3-oh. from 1 ^ .2 r. («> .L mol) Resaco'tophenon., 12.2 g (ol 'iol) Liithicrarbazinei acid methyl] - ester and ? Xnl 50 % - tiger Atiianol is stirred for 45 minutes 1 at _f - at 70 ⁰ O, then 125 ml Water was added and the reaacfitophconon-hydrazone-S-dithi ^ carboxylic acid niethvl-epter obtained (compound no. 48) was filtered after cooling. Yield: 2J ρ 30 ί of theory), P .: Crystals shrink from 173 ° C, decomposition at 17 ¹ J-ISO ⁰ G. After recrystallization from 50% aqueous. Ethanol and subsequent decolorization with activated charcoal are immediately obtained orange-colored hadels, which acquire a purple-brown color in air. F _.: IBO ⁰ C ίdecomposition).

Analysis (M = »2t> b.35)

Calculated: K 10.93 i S 25.01 j & Gefttndeni Έ 11.07 ^ S 25.01 J6.

- 35 -

.9098 85/1759

BATH ORIGINAL

Method Y

A mixture of 17.4 g (0.1 mol) of oxoraalone acid- ■

-dlethyl-eater, 12.2 g (O.l mol) dithiocarbazic acid-methyl-

"1

ester and 50 ml of ethanol is refluxed for 15 minutes. 200 ml of water are added to the yellow solution and the yellow oil which has precipitated is only added at 200 ml, then 100 ml Benzene shaken. The combined benzene extracts are with 100 ml of water washed over sodium sulfate and dried the benzene evaporates under vacuum. The weight of the residue is 27.25 g (98% of the total). The oxomalonic acid diethyl ester hydrazone K-dithiocarboxylic acid methyl ester obtained also (Compound No. 33) is cleaned as follows! dl © Subetana is dissolved in 50 ml of alcohol, precipitated with 300 ml of water and the yellow, non-crystallizing oil obtained in this way in one Desiccator dried over calcium chloride, /

Analysis (M = 278.36)

Calculated! N 10.07% S 23.03 * Gefujsdem W 9-.Θ5 # S 22; .. 87 '% method AB

. A mixture of 12 * 8 g (O.l mol) acetobutyrolactone # 12.2 g (0.1 mol) dithiocarbazic acid methyl ester and 50 ml Ethanol is refluxed for 10 minutes and the light- yellow solution added 30 ml of water. The eliminated yellow oil crystallizes quickly in the refrigerator * The crystals are filtered with a small amount of $ ® # -igem washed aqueous ethanol and dried. Yield ^ 21 * 1 g (91 * d.Tiuh P. 1 123 ~ 125 ° C. The melting point of acetobutyrolactone-liydrazone-H-dithiocarboxylic acid methyl ester Ir * I?) Increases the recrystallization from 65% igea » Ethanol nothing

Aaalys © (M »232.33)

Bereolmeti Jf 12.06 % S 2γ _Λ β0 #

I 11.89 # S 27.45 *

- 36 -

909885/1759

BATH ORIGINAL

ί i , t »· ■ *

: ♦ r I <»

fc * »» t _t ί - ι Ml

Procedure AG

17.8 g (0.1 mol) triketo hydrindene hydrate (Nlnhydrin) are dissolved in 180 ml of "70 ° C heated err dimethylformamide and 24.4 g (0.2 mol) dithiocarbazate-methyl - ester are heated in 100 ml of ethanol 7Q ⁰ C The solutions are combined and the red solution obtained is refluxed for 5 minutes. Triketo-hydrindene- -1,3-dihydrazone-N, N ^s -bis-dithiocarboxylic acid-methyl-thyl-θstθr separates on cooling (compound no. 105) made in the form of ruby, flaky crystals. The product is filtered, washed with 3 χ 30 ml of ethanol and dried at 50 ⁰ C dried. exploits 33.2'g (90 # of theory), mp! 206-208 ° C. (decomposition). The product is suspended in 300 ml of ethanol and the hot suspension is filtered.The decolorized substance melts at 209-10 ° C. (decomposition) ν

Analysis (M = 368.33)

Calculated: N 15.2Of ₀ S 34.80% Found: K 15.35 $ S 34.67 #

Procedure AD

The mixture of 29.4 g (34.5 ml · 0.3 mol) Mesltylöxyd, 50 ml abs. Ethanol and 12.2 g (oil mol) of methyl dithlocarbazlate are refluxed for 10 minutes and the reaction mixture is evaporated under vacuum at a temperature of maximum 70 ° C. "The yellow, oily residue slowly crystallizes and 20 g (90%) Mesityloxyd-hydrgzon-N-dithiocarboiicäure-methyl-estar (Compound No. 19) er; hold, Pt 68-7O ⁰ C. The product was purified by recrystallization from cyclohexane and at the same time decolorization with charcoal. The thus obtained yellowish needles scjhmelzen at 70-72 ⁰ C.

Analysis (M = 202.35). ·

Calculated j N 13.85%, S 31 "69 % found" K 14.02 ^ S 31.76 $ method AB _

The solution of 19.8 g (0.1 mol) of di-thiocarbaic acid -beftzyl-eöter in 200 ml of hot water ethanol is the suspension

-37 ■■ * ■■ ■ - .. - - ..

• i

of 13.5 g (0.1 mol) levulinaic acid calcium ae in 100 ml 90 days hot ethanol was added. The condensation reaction takes place immediately; on cooling, LS-vulinaic acid-calcium hydrazone-N-dithiocarboxylic acid-benzyl-eater (compound no. 108) separates out in the form of an oil. After cooling and rubbing the inner wall, the oil crystallizes in the form of snow-white crystals * The crystals are filtered, washed with 2 χ 30 ml of ethanol and air-dried. There are obtained 28.7 g (8 ² * theory) of substance which melts at 108 ⁰ C under water discharge. The substance is poorly soluble in water. By decomposition—. ρpunkt does not change after recrystallization from ethanol or water.

Analysis (M = 351.48)

Calculated: N 7.97 % ' S 18 * 24 # H ₂ O 10 * 25 * Found: W 8.08 % S 18.30 $ H ₂ O 9.93%

Procedure AF -

A mixture of 33.1 g (0.2 mol) chloral hydrate or 29.5 g (0.2 mol) chloral and 12.2 g (oil mol) dithiocarbazic acid methyl eater is melted in a hot water bath with stirring, and the brown liquid obtained becomes 200 ml water Light yellow resin separates, which is preferably treated a few times with water. The product is dried in a vacuum deslcator to constant weight. 24.8 g of a non-crystallizing resin are obtained (the yield is 99% of theory calculated on the basis of the oxo reagent). Chloral-hydrazone-B-dithiocarboxylic acid-fflethyl-ester (Ver ¹ -compound no. Γ) is purified as follows? The crude product is dissolved in dimethylformamide, precipitated with water, and preserving a Fiederschlag in the above ^ beschrlebenen way getropk ™ net, ·

Analyee (M = 251.60)

Calculated ι N 11.14 % S ■ 2§, 49. *

Found! ■ '_ JT 11.03 * S 25.22 %

- 38 -

3U8Ö9Ö / "I t

BATH ORIGINAL

"Verfahren AG '

22.2 g (0.1 mol) of acetophenone-p-sulfonic acid sodium salt are dissolved in 1 ^ 0 nile of hot water, the solution is decolorized with activated charcoal - "if necessary - and the mixture is filtered. 12.2 g (100 mol} of bithioearbaginic acid ffiethiy-eater . (. compound No. 42) are the FiItrat "ztiRefügt, the mixture is heated to the boiling point, then cooled acetophenone p-su] fonaäure-natrlum ~ hydrazone N- -dithiocarbonsäure-methyl-ester is _f in the form of light; the same _The fine crystals are precipitated, the crystals are filtered and washed 2 20 ι oί ethanol. Yields 27 3 g (84 it d.fh.K Fi the material first becomes dark and then decomposes above 230 ° C. The product can escape 4 times the amount of water to be recrystallized, yield? 92 % of theory.

Analysis {Μ = 326.40)

Berectmetr ü Β.5> β * S 29.47%

N 8.49 <£ S 29.32%

Procedure A

First, an ethanol-containing solution is Waeoer of Dithiocarbazin ^ äure-ethyl-eeters ζ * .. prepared as described in Example 2 by aug 1.5 mol (75 g) 100 $> - auegeht sodium Hydrasinhydrat-B-. dan product but nich ⁺ isolated. Spell is immediately 2:32 g (1.4 mol} p ~ nitro-acetophenone the solution thus obtained, at a temperature of 5 C was added and the ReaktiOnsgeinisch quickly with continuous stirring to 40 ⁰ C heated the precipitation of yellow crystals begins during the reaction. The mixture is kept for a further 5 minutes at 40 ° e, then cooled to 15 ° C, filtered and _{washed successively with 500 ml of ethanol s} 2 χ 500 räl water and 500 ml of ethanol. The crude product is purified by precipitation » Bas ~ o obtained pure © intermediate is the L'dstmg before 16O g of potassium hydroxide in ^- 1 liter © iskaltem water added · from the solution crystallized Kalluiasala the .Gemisch is poured in 6 1 eiskalte® water the main fraction of the Hied ers.. chi ages dissolves with the exception of 80 g of dark yellow methyl-p-nitro-phenyl-k et as ins (F .: 196-197 ° CK The dark

- J9 - '

909886/1759

■ '■' ■ ''"'" ■ · "■■' ■ '■''- ■ BADORiGlNAL

The bright red alkaline solution is acidified with glacial acetic acid until; the red color disappears with constant cooling and stirring. The yellow powdery precipitate obtained is filtered, then washed off one after the other with 2 × 1 liters of water and 2 × 500 ml of ethane oil and dried at 80 °. Yield: 246 g (62 $ of theory calculated on p-nitro-acetophenone), Fs 185-186 ⁰ C (decomposition) The p-nitro-acetophenone hydrazone-N- -dithiocarbonsäure-äth.yl-eater ( Compound no. 68) can be obtained from a 10-fold Men .- ^ e of ethanol with a yield of 84 # of theory. be umkriatallieiert, P .; 188 ⁰ C (displacement). The compound obtained in this way has no melting point depression when mixed with the compound prepared according to the method.

Analysis (M = 2HJ.38)

Calculated! N 14.83 h S 22.63 % '

Found r ... Έ 14.60 % 8 22.32 ί

Procedure AI

12.2 g (0.1 mol) of salicylic aidehyd, 13 g (0.1 mol) of finely powdered Dithiocarbazlnsäure sodium salt and 50 ml of ethanol are mixed together and heated the resulting suspension to a temperature of 50 ⁰ C. After cooling and filtering, salioylaldehyde-hydTazon-IT-dithiaarboneaure-liatrlujD-sals ?, a compound of the formula V, is obtained in the form of a light yellow, crystalline powder. The weight of the dry subetana is 21 g (theoretical weight: 23.4 g), Pr 253 ^° C. (decomposition). The sodium salt is dissolved in 200 ml of water and the solution is an equivalent amount vorMethyIjOdid or dimethyl sulfate was added at 10 to 15 ⁰ C. 18 g (80 %) of salicylaldehyde hydrazone-IIIithlocarbonaäurö-Jnethyl- ester (compound no. 37) are obtained, which sicii decomposes at 199 ⁰ C after recrystallization from ethanol. The connection <. No. 27, when mixed with the products obtained according to methods B and L , has no decomposition point depreeelon.

Dlthiocarbazinsäure-natriumaalz is prepared as follows t 84 g (2.1 mol) dissolved in 100 ml Natrluiahydroxyd

- 40 -

909885/1759

ν, <'; e _A - BADORJGINAL

Waaaer the solution of 100 g (2 mol) 100 # -igem hydra-. '

"zinhydrat in 600 ml of abs. ethanol was added, the solution cooled to 0-5 ⁰ and G dropwise LOOE g (128 ml ', 2.1 mol) carbon disulfide in" of- added for two hours under stirring and cooling. The suspension is then stirred in a salty egg bath for 2 hours. The light yellow sodium salt is filtered off with 2 χ IQO ml. Washed ethanol and dried over calcium chloride in a vacuum desiccator. Yield: 200 g (T7 # of theory).

The sodium dithiocarbazina acid can be replaced by a corresponding potassium salt (J. Prakt. Chera. (2), S3, _{59/1916 /) »NH 4} -SaIz (J. Chera. Soc. 119,? 64/1921 /), or hydrazonium salts (Ber. 2 £, 58/1894 /, J. Prakt, Chem. (2), ^ 2, -486 / 1895 /, Ber. 41, 1099/1908 /). ·

Procedure AJ

, In the reaction of hydrazones with NatriuinpuLver or sodium "in the presence of an inert solvent a mixture of Eono-sodium and di-sodium compounds can be obtained. If the mono- ^ Natritini compound is prepared in the presence of carbon disulfide _s is thus obtained one the compounds of formula V, for example

4.2 g (Ό.11 mol) sodium amide is added in portions to the solution of 13.4 g (oil 1 mol) acetophenone hydrazone in 6.0 ml anhydrous carbon disulfide. The mixture begins, according to the developing heat of reaction, with the release of ammonia The reaction is over in 30 minutes. After cooling, the precipitate, which consists for the most part of acetophenone-nydrazone-hif-dithiocarboxylic acid-sodium salt, is filtered and washed with 3 κ 30 ml of anhydrous ether. The 20 g of sodium sala obtained is dried and dissolved 200 ml of water _e. decolorized with Ig activated charcoal, filtered and the piltrate within 20 minutes 7.6 ml (0.08 mol) (dimethyl sulfate added dropwise, with stirring, and ice cooling. The aoetophenone-hydrazone-N- ^ dithiocarboxylic acid-methyl ester (compound no. 53) separates in the form

- _ «■ - Ί909 & 85/1759

- BATH

193481 »

of "yellow flakes, from ...""They are filtered, washed with water and dried. 15" 7 g (70%) of the crude product are obtained, Fs 147-150 ° C. After recrystallization from ethanol, can bright yellow, shimmering, fine! threads can be obtained »F.» .149-150 ⁰ O.- The compound obtained in this wine, mixed with the substance prepared according to method B, has no melting point depression.

Procedure AK

2.3 g of sodium powder are added in portions to the solution of 13.4 g (-0.1 mol) of acetophenone hydrazone in 100 ml of abs. Aether was added while stirring and cooling in a salty sis bath. The w stirring is continued until the disappearance of sodium.

Then the solution of 14.05 g (0.1 mol) of DlthlocarbonsHure- -ethyl-ester-chlorld in 50.ral abs. Ether is added dropwise to the solution over the course of 2 hours, and the reaction mixture is stirred for a further 6 hours at 5 ~ 10 ° G. The mixture is evaporated and the residue treated with 200 ml of water. "The crystals are filtered, first washed with water" then with 3 × 10 ml of ice-cold ethanol, yield 11.4 g (48 % of theory) Acetopbenon-hydraaon-N -dithJOiarbonsäure-ethyl-ester (Vor- ■;. binding Nr / 73). The substance melts at 129.5-131 ° C after recrystallization from ethanol, and shows no Schmelzpunkrtdepression _s if it is mixed with the compound prepared GEMMS Yerfahren D. .

Yegfahren AL

11.5 g (0.1 mol) thiophosgene are dissolved in IpO ml abs "ether and added dropwise with stirring and cooling in a salty ice bath to the acetophenobi-hydrazone sodium salt prepared according to the procedure ÄK" 14.6 g (0.Ί mol) dry benzyl mercaptide -Natriuasalz- are immediately added in portions to the mixture obtained. The mixture is evaporated and the residue is heated with 200 ml of water. The crystals are »filtered» first with water »then washed with 2 χ IJ ml of ethanol. Yield 12.3 g (41 % of theory) Äeetophenon-ij ^ drazon-S- ^ ithlocarbonsäure '-' beiizyl 'ester (compound Ir «,

- ■ '■■' ■ ". - 42—" .-. ■■ - '- ■■ ·'

ORIGINAL BATHROOM

* V

* t

1561 are preserved. The Subejban.a melts at after recrystallisation from aqueous ethanol and sodium 9O.j & comprises, substance prepared with ά & τ geaiME Method E mixed no Schmelzpisiiktdepresaion on.

Analysis Cl - 300.45)

Calculated 1 9.33. * S 21.34 * Found * I 9.11% S 21.57 *

The mixture of 13.4 g of C 0.1 mol) acetophenone hydraonunci 49.3 g CO 3 mol) Trithiokohlendloxfd-ethyl-egter are boiled over a hot water bath for 10 hours * piert, the mixture cooled vtnä filtered in an eieüoldem Sustassd 11 g C46 <& d.Th.l ύ @ Β crude product are obtained, which make recrystallization as ethanol melts at "129..5-131 ⁰ C · The acetophenone liydrasoii . ^ mixed -dlthlocarboiisaure ihsl-Sister (compound Hr. 73Ϊ weists feergeatellten with the gemäß'Verfahren B substance, no Sehmelzpunktdepressioii on _o

Corruption ''

This "method is advantageously used when the oxo compound can only be isolated with difficulty, but the blood-oil derivative can easily be excreted.

12.2 g (0 ·! Mol) oithiocarbazic acid methyl ester g © - n

Dissolved in 50 ml of hot ethanol, the mixture of 21.1 g of 0.1 KoIi ^ friiiii-S-aldehyde-natriuni-bieulflt in 100 ml of water is added. A solution of 10.6 g of Hatriuilacarbonat in 100 ml of water is added to the reaction mixture droppinsweie® ₉ with stirring within τοκ 30 meows at a temperature of 50 ° C, among other things. the resulting mixture for an additional 30 minutes. 50 ° ö tubed. After cooling, the yellow tan product is filtered »washed with 3 × 30 ml of Wb, bs & t and 20 ml of ethanol, yield 16 g '(76 % d.Tfa.i» F.ι 173-17? ° G (Zersetzungh Der Pyrldin- - 2-aloehyde - li5 ^r draEon - if-dith £ ocarbonsäure "inethyl-ester (compound Mr * U) seraeta-t at 180-182 ⁰ C after Umkristalli-

- 43 - ■ ■

909885/1759

eggs ana ethanol. Light, cream-colored, loose needles are obtained.

Analysis (M = ■ 211.31-)

Calculated: N 19.89 $ S 30.34% * Found »K 20.02 % S 30 * 43 # Method AP

Quinaldine is oxidized with selenium dioxide in a Dloxanmediura (JACS 63, _{2654/1941 /) 8} then quinoline ~ 2-aldehyde is reacted with dithiocarbazic acid esters of the formula III without isolation in the following way}

14 * 1 g (Ol mol) quinaldine dissolved in 23 ml of dioxane, the solution of 13.3 g (0 * 12 mole) of selenium dioxide in 120 ml of dioxane and 5 oil water dropwise with stirring at a temperature of 45 "5O ⁰ C for 15 minutes added, the resulting reaction mixture is boiled for 1 hour under Hückflu0. To the still hot mixture containing defl · selenium boiler add 2 g of activated charcoal and filtered. The filtrate is concentrated to a quarter of its volume under a stream of Np. 9.8 g (0.08 mol) of dithiocarbic acid. Ethyl ester dissolved in 100 ml of ethanol is added to the residue, and the mixture is heated to the boiling point of the alcohol. During the reaction, methyl quinoline-2-aldehyde-hydrazone-F-ethyl-carboxylic acid methyl ester (compound no. 79)

in the form of an ocher yellow powder. The mixture is cooled and filtered, the crystals washed with 3 × 20 ml of ethanol. There are 14.3 g of the desired product obtained (55 # d, Th _f calculated on the quinaldine), Fi 186-189 ° C (decomposition) .The substance is dissolved in Dimethylfoiimaiaid at 90 ⁰ C and precipitated with water. Daa purified product melts at 192-194 ⁰ C (decomposition) and has, with the compound prepared gzmäS method B mixed no SchiaelEpönktdepression on.

Analysis (M = 261.3?)

Calculated f F 16.08 % S 24 * 53 #

Found «K, 16.09 <*> S 24.55 ^ 6

- 44 -

90 9885/175 9

BATH ORIGINAL

■ AR procedure

The mixture of 25.5 g (oil 1 mol) of sajirem troplnon fumarate, 12.2 g (0.1 mol) of methyl dithiocarbaztnate, 100 ml of isopropanol, is refluxed for 15 minutes Washed amount of ice-cold acetone and dried at 65 ° C / 2 mm Hg. For example, 26.9 g (75 i of theory) tropinone hydrazone-N-dithiocarboxylic acid methyl ester (compound no. 58) are obtained, Ps 158-160 ° C. (decomposition). The above salt decomposes at 16 ° C. after recrystallization from ethanol and drying to a constant weight. -. -.

Analysis (M = 359.48)

Calculated: N 11.69 % S 17.84 # Found: N 11.53% S 17.66 $

Procedure AS

15.05 g (0.05 mol) θα »ui-dibromo-quinaldln 6.8 g (0.05 mol) CH ₃ COONa.3HpO and 45 -nl dimethylformamide are placed in a 250 ml round-bottom flask equipped with a stirrer, reflux condenser, thermometer and oil bath Minutes with stirring up to an internal temperature of 135-140 ⁰ C heated. The solution of 7.19 g (0.57 mol) of anhydrous potassium carbonate in 15 ml of water is added to the mixture at / the same temperature. The solution obtained - containing chloroline-2-aldehyde - is cooled to 65.degree. 5. 5 g (0.045 mole) of 'pulverized Dithiöcarbazinssure-methyl * - ester to the mixture are added and the solution cooled to 25 ⁰ C. 70 ml of water are then added dropwise to the mixture over a period of 30 minutes, while stirring and cooling with ice. Öhlnolin ^ -aldehyd-hydrasson-K-dlthioearbönsSure- -methyl-ester (compound Kr ₆ 73) is excreted in the form of a yellowish brown powder. The pest substance is filtered and washed with 2 × 25 ml of ethanol. The compound obtained in this way melts at 192-194 ° C (decomposition) and shows no melting point depression, mixed with a product prepared from geiaMB Example E,

. -. , - 45 ~
'90 9 885/1759

Procedure AT

Isolating pure 4-acetyl-l-naphthol (free of oc-naphthol) is quite difficult »if the connection is made according to the method of L. Vanino: Handbuch der ρräparati-ven Chemie Volume II. Page 514. Our process enables the production of 4-acetyl-1-naphthol-hyärazone- -N-dithiocarboxylic acid methyl ester (compound no. 121), without to isolate the pure Oüto connection

14.4 g of anhydrous sink chloride and 15 rals fresh

k distilled glacial acetic acid to 14.4 g (Ό.1 Hol) * <- together naphthol and the Reaktionsgemi-sch boiled in an oil bath at a temperature of 125-13O ⁰ C for 2 hours under reflux. The resulting dark red, hot solution is poured into 100 ml of ice-cold water. 4-Acetyl-1-naphthol containing c-naphthol varnishes precipitates in the form of brown granules. After dismembering, filtering and washing with water and intensive suction, the moist crude product is dissolved in 100 ml of hot methanol. The solution is clarified, 12.2 g (oil mol) of methyl dithiocarbazate are added to the red solution thus obtained and the mixture is heated to boiling. After cooling, the dark yellow precipitate is filtered, powdered and washed with 2 × 30 ml of methanol. Yield: 23.2 g) (80 % of theory 1 »Ps iao-185 ° C (decomposition). In practice, the product can be dissolved in most organic solvents. The substance is purified as follows: the crude product is purified in a 4- times the amount to 45-50 ⁰ C heated DimethyIformamid dissolved, the solution decolorized if necessary, and the mixture to as "twice its volume of water NAIT / erdünnt ₉ and the withdrawing yellow Kristallpulvsr washed with ethanol. exploits 95 # ^ .HI." F * s 188 ⁰ O (decomposition). When mixed with a compound prepared according to process I, the fine subatanss has no melting point depression.

Analysis (M ■■ »290.41)

Calculated ι N 9.65 56 S 22.08 ^ 6 Found: Έ 9.39 * S 21 »83 ^

BATH ORIGINAL

Procedure AU

The solution of 2 g of sodium hydroxide dissolved in 10 ml of water is added to the mixture of 48 g (0.5 mol) of fufurol _s 220 ml of water and 32 g (0.% Moll acetone, while cooling with bis. The reaction mixture obtained is added for one hour stirred then 4 ml of kois. hydrochloric acid added and heated. The crude® furfural acetone obtained by aldol condensation precipitates in the form of an oil? At the same time, the suspension of ditbiocarboxylic acid ester in ethanol-water is prepared according to the Weis® described in example 1 "By starting out from 30 g (0.6 mol) of pure mydrazine hydrate · The suspension obtained is added to the oily crude furfural acetone. The Qemiscfa * Itü is heated to 50 ° under ÜUhr @ n» then cooled »filtered and the Feetefelaetanisen is washed with water and dried . 73 S, i62. ^% S.Th »! the Hohproduktes be obtained. FurfurQl®o © ton'4iydrfeson-H ° ~ dithioöarlsonsäure- -ffiethyl ester separates in WOSM by schimm®vna @ n _t brick-red fins to Umkristalli ei & ren g @ s ^ £, ferfahr @ n A from »? .i 136-139 ⁰ Ce The substance has _s rait ά @ τ according to the process A $ compound vensisciit no melting point depreesion.

- 47 -

9 09885/1759

BATH ORIGINAL.

Table 6

(O O

co

OO

cn

OT

¹ I.

2. 3. 4 ·

5. 6 .. 7.

8. 9

10. 11 ·

15. 14.

yerbia- Btto «Formula of the compound used as a starting compound- Hr. sKS formula (I) dete OxoyVerb.

(R —CQ-Ii) or the corresponding _ ■ the derivatives

Process (yield,%)

F ⁰ C

(Cleaning procedure)

C ₄ H ^ Cl ₃ H ₂ S ₂ ^C 6 ^H 6 ^N 4 ° 3 ^S 2

⁰ Ai ¹ A '

^C 7 ^H 8 ^N 2 ^OS 2

Chloral or chloral hydrate

Alloxan

n-But yral dehid

Methyl ethyl ketone

Parfttrol

Thioph © n-2-aldehyde

-glot axsltare « HBOBLOaat r iuiaaalz

^, 2 ^ 0 Lttmline & iires

Calcioma

Lfivulinattore Cyclopentanone

Pyridis-2-aldehyde Pyridine-3-aldehyde

CH ₃ AF (99) resin 15 ° (k) CH ₃ C. (86) over 260 ° (*) Γ (90) oil, freezing point: (a) CH ₃ J (71) 69-71 (b) CH ₃ A. (93. 5) 152-153 (b) CH ₃ S. (94) 173-174 e.g. (b) CH- V (83) 192 Z _e (s)

CH ₃ CH ₃ CH ₃ CH ₃

Π (90) 157-158 Z,

A (76) 117-120

^ (91.5) 157 T.

J (82) 145-146

F (88) oil

E, AN, AP 180-182

(90, 76, 52)

E (93) 197.5 Z _e

Table 6 continued

Verbin— Btto.Formula of the

connection

No. mttfi formula (I)

OxogVerb used as the output connection.
(R ^ -CO-H ^) or
the corresponding. Derivatives

Έγ method
(Yield, ^c , \

_FC (cleaning process)

CD οι 15th , φ ' b 16. Φ
OO O 17th CJt 33 18th —I Q 19th i S ¹ ■ ' 2ö; $ ■ ■ 21. I. 22 25 * 26th 27 28.

Pyxidine% aldehyde
2-furyl-methyl-ethyl-ke t on
Acetobutyrolactone
Acetoacetic ester

Isbpropylidene acetone
(Mesityl oxide)

Cyclohexanone
MetSlyl-t. files yl-ke tone
5-methyl pent san-2-one
p-bromo-benzaldehyde
p-chloro-benzaldehyde hyd

CBL • CH ₃ CH ₃

CH ₃ CH, CH ₃

Benz aide hyd-p-sul fön- CE ₅ acid sodium

p-nitro-benzaldehyde

o-Hydroxy-benzaldeliyd ^ CH- -aaiizyLaldehyd ^

ffli-Hydroxy-be nz aide hyd CH ₃

E. (90) 203 Ζ,

A (91) .131-132.5

AB (91) 123-125

J (76) 62-65.5

AD (99) 70 ^ 72

J (70) 107-108

I (79) 103-105

F (90) oil

A (69) 194.5 Z.

A (82) 174 Z.

AG (77) over 200

A (91) 198 ZL.

B _r L, AI _/ 199.S5.
(96, 88, 80)

A (70) 173 Z.

Table 6 continued

o ■ 2 Q Z

Connect Btto. formula the As output ver "* Procedure F. ⁰ C manure Connection g e- Use binding E (Yield,#) (Certification process) No. measure formula ( I) de te OxogVerb. (E / -CO-E * ") or which correspond the Deirivate

29th 30 31st 32.

34. 35.

.36 * 37.

38.

40

8 ° 'Λ

p * -Hy droxy-benzai de hyd CBL

CBL

H-

2-acetyl-pyridine

3-acetyl-pyridine

4-acetyi-pyridine

OxomalongSure-diethyl- CH-

ester ·. *

Cycloheptanone.

Acetyl-aeetön

Heptan-2-one.

CnIoral or chloral

A A T

hydrate

Cl

"0 * 2

Chloral or chloral hydrate

3 _t i4-4äetßyleadiöxy-ben- CE »zaldehyd (pipöronal) *

p-bromo-aöetopheaoa C

p <= € hl or «acetophenone G

Acetophenone-p-sulfon-CH,

acid s-N atrium ^

(65)

(73.67) (73.5) (71) (98)

(76.5)

(87). (.100)

(99)

(95. *)

(73) (79)

171.5 Z. 131-132.5 171-172 Z, 18t oil

119-120 135-136.5

75-77

from 189 Z.

above

Cp)

(D)

Cf)

Table 6 continued

V> rDin- Btto »Formula der

connection connection

Kr. "Forael (I)

43.

45.
46.

47.

48.

50.

co 52 O co 00 QO 53. cn 54. O -4 O (O 55. RIG 5 "» > Γ

^C lAl * 3 ° 2 ^S 2. ⁰ I (AA ⁰⁸ Si

As Aaegangsverbindamg used OxowVerb. (E ^A -C0-R) or the corresponding derivative rate

Move α
(Yield ^

F. ° C

(Cleaning process

Furfural acetone

CH „ηηΜθ t feöxy ~ be nz al debyä CHL

4-Eydroxy-3 ~ me t ho.xy- benzal dehyd (Vanil in) C &

2.4 ~ Dihydroxy-acetοpaenoE «

Pheaylacetaldehyd or CE-Pheaylacetaldehyd-di- - ^

D (77) 194 ZS ₆

A ₉ AU (86, 62.5) 133-139

f (83) 154-155.5

S (93) 155.5 .Z.

I (88.5)

I (90)

X (75)

S (73) 132-133

A (96) 174-175

B, Q (93, 58) 150 Z.

180

Acetophenone.

CE, B, 1, AE, AJ (93.94, 149-150.5 ^ 66.70)

JÜ-acetyl-6-raet ^ yi-pyridine

CE-

3-acetyl-6-methyl-pyridine Dihydro re βο rc in 'CiBL

(87.5)
(76)
(87)

122-124 152-153

171 z.

ibi (a, b,

(b, ui 0 »)

(b

(b ^ 00

U ο co

Table ό continued

VJl IO

Verblm- ütto.FormeL der

dttng connection

Mr. bias formula (I)

57, 58, 59.

60. 61 * 6a.

65. 64. 65. 66. 67. 68. 69. 70.

wT läO It

As output βύ & τ- binämxg used Oxo »Verb. (R -CO-S) or the corresponding S-dea derivatives.

Br procedure.
(Yield, %)

F. ⁰ C

(Abxe veri)

⁰ AA ⁰⁸ I.

Tropine ». _k Sasires Tropinoa ^ -foaarat

acroleiite

Sis & ydrin. (Bie ozone group Position I is set)

Acetone Cl

E ^ -diacetyl-pyridla / CH-

149

161 Z.
116-117

74-76
oil

165-166 t.

155-166 ζ _β

134-135
171.5 Z.
111-113
168-170

188 Z.

β.

174 Z.
159 Z.

(i)

(a)

(k)

(a, b) (c) (b) (k) 1>) 0 »)

Table 6 continued

manure

No,

».Formula of the
Compound according to formula (I)

Al3 output connection used Oxo.sVerl) .. (R ^ -CO-E) or the corresponding derivatives

Process (yield, ^

F. ⁰ C (Re inignng sye rf ahr en)

72. π * 74. 75. 76 77. 78. ■ m ■
CP
φ
it?
cn 79.
«0.
82 · m
m 813.

As

acetone
PUenyla.ce tone. Acetophenone

p> -Me. t hy 1 —ace t ο phe no η Propiophenoa

CH ₃ E

AJ ₇ Al ₅ D

(86, 48, 46)

(61)

72,

dehydration

Ace tondicarboxylic acid -diithyiestner

FurfBtrol

ΡΜιιοΙΙιι- ^ βϋίαβ ^ ά or CH, the corresponding. Derivatives

Acetophenone

J
R.

1"

Besrial acetort

ro— ρζ, - ^ sc e t amino— acetophenone

CH ₃
CH ₃

D.
E.

(86, 60)

(98)

(72) (72)

(97.55, 74)

(74) (82) (72) (73)

(97)

100 ^ 101 »5 129.5-131

138-139 122-123

183 ^ 184 Z ,. 92 ^ 94

156 ^ 157 192r-194 Z.

IO7-IO8

165 ^ 166 ζ,

1 ^ 6-127

184 Z,

223 Z.

(to) (to)

(to) (to)

(c)

Table 6 continued

Vesrbin- Bttο.Formula of the dung compound ge ^ -

No. dimension formula U)

As a starting connection, used OxosVerb. (R ^X _CO-.E-) or the exit speaking the derivatives Terfabxen (yield,

F. ⁰ C

(Cleaning ver

85, 86, 87. 88

89

91

93,

95 ..

97.

TereEpSith.alaldeliyd

p-chloro-butyxophenone

3 * 4,, 5-Trimetb.os: y-benzal-CBL deiiyd ^J

ρ = 4ί e tlLQxy-pae nylac e toa

223 lines 171-172

Benzaldehyde propiophenone

DL-10-Eampfersulfon.saurea CE. Potassium *

Camphor, ce

4,4-Diiaethyl-cyclohexane.-CE-r-l, 3-dione (Dimedon) ^

2-n-butyl-cyclohexftnon acetone. 180.5 Z. 83-84 119-1 ?! Λ

(c)

Gf

te

■ a

M - *

β p

fcfl W

ο ο

Io

-P U

H ■ * -!

I »!

- «Η β
«Rf

, β .O k

"2" ■ * ♦ A ^- ^ ^ O

OS

GD

m »4

« GO S. 09 H
9 H
I. <s »
H Ώ H

* »Η uv Ot

Oi! 4

et vp

Ch

CS

“ O OH

H O .H

β β-

O O

H 4

ty »v ©

GO

ί ^V "ίΓ

W)

® Ή β.

• Η «j r-ί»

βίο ο

ϋ4 * ο »Φ.

i * 5 αϊ-

odd oj)

Se) tfe M

Ol M

v ©

r-4
H

»N

HO

a-

H.

909885/1759

BATH ORIGINAL

Continuation of the table

VJI

to
ο
co

connection no.

Btto formal of Connection

gg mäB formula Tl)

g T

112, 113, 114.

115, 116, 117, 118, 119. 120, 123 ..

125.

124. 125.

As an output connection used OxosVerb. (ir-CO-ir) or the corresponding derivatives Ir procedure

(Yield, %)

F. ⁰ C

(Cleaning procedure)

Aniaalacetone Propiophenone

H,

BL-p-Nit ro-ö £ -ac e t amino-CBL F, Z - ß- · hidroxy-propiophenone ^

2,6 ^ diacetyl-pyridine CE »K

2,3-ßiaethoxy-phenylacetone CBL A acetone

Pyridin-3-al defayd 2-furyl-methyl-ketone Cl- ^] 2-Bemzo il-pyri dia

2.-Furyl-fflethyl ^ ketone 1-Ace tyi-a ^ pt hai in. 2-Acetyl ~ oapht hai in

2,3-dichloro-4-butyrilphenoxyacetic acid.

Glycdhexane.

(63) (77) (62, 84)

(92) (77) (82.5) (80) (72) (70)

(95, 90) (93) (90) (96) (78.5)

(90.5)

L55-I56 84-85.5 168-169 Z.

195 Z.

123-126

97-98.5

172-175

130-131.5

122-123

188 Z.

132-154

111-112

178 lines 195 lines

116-118.5

, CD

Continuation of table 6 '

OO CO OT

Connected Btto.Formel d & r dung connection according to formula (I)

135, 136.

137. 138.

139.

127. C ₁

128. C-,

130, 131. C

As - output connection used Oxo «verb. (H-CO-R) ο de r the corresponding periyate

Process (yield ^)

(R & i

F. ⁰ C

res ·· Sodium ?, ','' _: Cl- ¹ p ^ nlor-benfcal denyd

(Sal iöyl aldenyd) BenÄäldeiiyd

Be ήζ aldenyd- ρ- sul f ο η-s & ures sodium

2-ethyl-pyxidine

^ y (Salicylaldeiiyd)

Benzophenone '

S ^ -ä.c e tyl - pyri din:

(94). (93) (7Ö.5) (96)

(95) (92.5)

(9 ** 5) (9ö)

(92) (90)

(90)

oil

over 175-177 "

157-159

190-192: 185 ^ 186 over 200;

181

(c)

Cn)

(i)

(b) Cb)

Table 6 continued

Connected Btto “Funnel of the
connection connection ge no. measure formula (I)

As a starting compound used OiosVerb. (ΈΓ-ΖΟ-ψ) or the corresponding "recnett-

denJDeriTate

procedure

F; ⁰ C (Eexnig-entrusted)

i- (2i-methylene-btttyril) -phenöaty-e acetic acid

Cyclohept anon
acetone

CH-

144. C

145 * C

146.
147,

148.

S ₂ «C-Metayl-iS-Cp-itopropyl- CH-

-paenyi) -p! föpionaldehyd ^J.

Lo ³³ I ^ lHgSaO-S ^ ^SQ * ο phenon- p- sul f onsaare s

Benzil

p ^ -Me thoxy-benz al dehyd

Cl- ^

Furiurol-aeeton C.

phenon (Re »acetophenon) Acetophenone

151

Acetopiienon-p-sulfoa- / Λ-CHL gatti? Öfl sodium «/« ■

pp gatti? öfl sodium

-pyxiditt Benzoin

CH ₃ B F (97)

(9 ^ .5)
(92E)

(55)

(96) (78)

(91.5) (90)

m)

(9 *) (94)

in the)

(93)

160 * 163 Z>

134 * 135.5 104ν 5 * 106 89-91

over 200 111-113

149-151
129-131
129 * 131

151.5-155
Over 200

126 * 127
108-110

(*) ■■

(b) Cb)

it) Cb)

Cb)

C ») Cb)

(b) Ci)

Cb) Cb)

the table

manure

No.

the Al · Aesg &sgever-; β- feiadsng used-I) dete OxonVetb, (IT-CO-B ^) or the corresponding- '_dea derivatives P. ⁰ C

O CO CD OQ (Π

155, 156, 157.

159, 160, 161.

163

165 * C

166. C

167. C

168. C

CH-CH-

2-Ac e t yl-3 ~ rae fcfeyl

Q-CH ₂ S

# ° Piperidiffio «» pr9pio- ECl CH,

2-acetyl-pyri dia acetone

deces.-4-oa ■ ~

Ninhjrdrin. (Oxogxuppe in JT ^ position 1 is amgesetact)

P E. F (92)

(85, kl) 135-136

(95) 120-121.5 (81) 104-105

(75)

(78)

(90) (72) (91) (83) (98)

(76)

116-117 104-105 · 5

128-130 & h 166 t.

92-9% 76-78 oil

147

U) (b)

"OO

U) U)

U ₉ b)

(b)

Table 6 continued

CD OD OO

Connection Btto.Formula of the connection according to & JI No. formula JI) -

169 .170. 172. 173. 174; I.
σ \
O 175.

176

178. C ₃

179. C. 180. 181.

182

8 ^a i5 ^N 3 ^S S

OxoxVerb used as the output connection. (B-CO-R ^) or the corresponding derivatives r R ^J process (yield,%

F. ⁰ C

(Cleaning process)

Indo1-3-aldehyde Indole-3-aldehyde

Benzal-acetophenone (EAlkon)

Acetophenon w — Be nzyl — acβ t οphonon 2-acetyl-pyridine. E.

2-0x0-9,10-dimethoxy- -1,2,4,3 »6,7-hexahydro- -llbH-benzo (a) quinolisine

Acetophenone ** - ethyl caprophenone Quinoline-2-aldehyde. Cl quinoline-2-aldehyde Benzoin acetate

L- / le-benzoyl-

styrene oil

p-Me t hozy — phe nyl — ac e t on.

¹¹ ■■■■ - '■ ■ CL

Acetophenone

(93.5) (97.5) (94)

(35) (84)

(83) (90)

(76.5) (90) (98)

(97) _:

(96). (74)

C74) (8S) "

174-176 180-181 118-120

134.5-136

99-101

147-150

178.5

80-82

92-93

17? -180

I76.-ISO

80-82

144-146

76-78.5. 124-126.5

(b) Ct ») (c) -

(b)

(b)

(b)

(p) O (k, m) (k, m)

U)

(b) OO

Table 6 continued

Verbin- Btto.Formula der dungverbindozig ge

No * measurement formula (I)

OxogVerb used as the starting compound. (B - CO-B) or the corresponding Derivatives Ir process (yield .3

F. ⁰ C

(Cleaning process)

184

186, 187.

■: ■ »
grv

189. 190.

192.

195.

194

^G 19 ^H 18 ^C1 % ° 2 ^S 2

■ 2 ■ £

2-ethyl-pyridine (CH,)

oc-formyl-3,4-dtme t hoxy ^ pheny1— acetonitrile

Dibe nzal — ac t on

oC-F ο rmyl-phenyl-C I- / '■ ^ -es sig acid-ethyl- ester' ■■ ■■; , .. '',

DL-p-nitro-oCr-ace-

—Propiopherion dibenzoyl methane

(CH ₃ ) _e

Acetophenone

2-acetyl-pyridine

CH ₃ - (CH ₂ ).

2-0x0-3-8 ^ 1-9,10 ^ 1- 'CH-. met ho xy-1,2,3,4,6 * 7-hexahydrο — 1ibH-benzο (a) quino lisin ■ '".., ■■.;. ■:;. ■ ·. ■; ^ ₁ ""' ¹

2-0x0-4 _T 4-dimethyl-9,10-CH ₃ dimethoxy-1,2,3 j 4,6 ₁ J- hexahidro-IIbH-benz6 (a) quino- lisine; ■; ■ /; . ^·:; , ■■; ■■. ■.

Acetophenone CH ₅ - (CHg) J- ^

X
Y

(94.5) (50)

(80) (• 99)

(65)

(90)

(86)

(65) (81)

(79) (78)

133-134 135-137

145-146 oil

160-162 t.

139-141 128-130

121-123 160 Z.

152 ζ »

127-128.5

, Ce)

Cg)

(η) (b, Sr)

Cc) (b)

(b)

(b)

(b)

Table 6 continued

1 * <£>
Ö Verbia- Btto.Formula Connection g
measure formula ( the as exit R. X = J procedure (72) - {65) F. ° C (b) 1 (k, r) • ν * »
S. IO
CO manure use e- binding (Yield, ^) (94) (97.5) Cb) («Λ S.
"Z ^: f » No. I) dete OxoxVerb. Gl - ^ - CH ₂ (78) Cb) (b) (»- ^ CO-H ■) or Cl- ^ VcHo (80) (94) (Se iaiguag s procedure) (J) Cb) ι » '_ .. M _- _ πι _ ^ ^ i ^ which correspond \ s / - ! 'SS) "..: 'Ca)' C ₂₀ H ₃₃ N ₃ S ₂ the derivatives CH ₃ Q-CE ₂ C. '..' (71) ■ (65) (J) 195, C ₂₁ H ₃ IN ₂ S ₂ Laurophenone nC ₁₂ H ₂₅ Ji-C, ^ EL ₅ J, P. (SO) 19.6 · 2-acetyl-pyridine ⁿ - ^C 12 ^fl 25 L. (78) (S6) 62-65 (b) 197 Acetophenone Cl-OcH ₂ S. (88) 91-92 (r) CD
Ca) 198 eC-Μθ t hy t-O-be nzo il- Ns / 16 ^ 5 - 87-89,. 00 etyrene \ f ^ -CH ₂ 'S 142-144 ...O 199 * ^C 24 ^H 40 ⁱⁱ 2 ^S 2 «L-Ue thyl-ß-benzo il- CD C ₂ -H ₂₀ N ₄ OS ₄ styrene CH ₃ C. 122-123 I. 200 Palmitophenone AC 201 Ninhydria (1.3 Oxo- 63-64 (S3 C ₂₅ H ₂₁ ClN ₂ S ₂ groups are around 189-191 I. CH ₂ Cl NS set ) P. 202 25 ^ 23 2 5 Dibenzal acetone κ 205 925 ^ 5 ¹ SS '.,' 2,6-diacetyl-pyri- 149-150 C ₂₅ H ₄₂ N ₂ S ₂ din K 198-199.5 204 ^C i6 ^a 36 ^ll 2 ^ll 2 2,6-diapetyl-pyri-
din D. 205. C ₅₅ H ₆₂ N ₂ Sg Acetophenone 190-192.5 206 C ₃₉ H ₇₀ N ₂ S ₂ LaurophenOn ο ¹ . ^: · 38-90. , ' away?. Palfflitophenoa v.105-107 ',:' Palmitophenone **** ·? ■: "■ '' ν ■■■ fMo'V ¹ : ■; ■■ ϊ:

Information on table 6:

Z. decomposition point

P. Freezing Point

Lower case letters, in brackets = cleaning method (al recrystallized from methanol

i "

IbJ recrystallized from ethanol (el urakristallisiert from aba.ethanol

(d) recrystallized from isopropanol

(e) dissolved in the mixture of benzene and aba. Ethanol (4: 1), and reduced to a quarter of its volume under vacuum.

(f) recrystallized from water

(g) suspended in 80% hot ethanol

η - ". (hl recrystallized from 65 jb-lgem ethanol

(i) recrystallized from 75% -igenr ^ ethanol

(jj suspended in hot methanol }

(ki from dimethylformamide solution precipitated with water ^% - -

(1) suspended in warm (80 ° g) dimethylformamide Cm) treated with hot chloroform (not precipitated from athanol solution with water (pi recrystallized from 50% ethanol

(r) suspended in hot ethanol

(s) recrystallized from 90% ethanol

(t) recrystallized from the mixture of carbon tetrachloride and methanol (9il)

( ^Y u-) dissolved in 5% sodium hydroxide and old acetic acid precipitated

(v) recrystallized from cyclohexane

(s) recrystallized from the mixture of benzene and cyclohexane (lsi)

⁶³ 909885/1759

Claims (4)

PATENT CLAIMS > . R for hydrogen, an optionally by alkoxy, carboxy, Carboxylate, carbalkoxy, or amino, alkylamino, dialkyl ^ amino and trialkylamino groups, or by the pharmaceutical Compatible acidic addition salts substituted straight or branched alkyl, alkenyl, aralkyl and Aralkenyl group; an optionally mono- or polysubstituted one Phenyl group in which the substituents are the same or are different, namely halogen, alkyl, alkoxy, acyl, Hydroxy, carboxy, carbocylate, sulfonic acid or carbalkoxy mean? an optionally mono- or poly-substituted one heterocyclic group, e.g. pyridyl, idolyl, quinolyl, thienyl or puryl, in which the substituents are the same or are different and indeed halogen, alkyl, alkoxy, acyl, / * hydroxy, carboxy, carboxylate, sulfonic acid or carbalkoxy mean and I 2 "R for hydrogen, optionally one of the definition of R as indicated substituted straight or branched Alkyl or aralkyl group, a carboxy or carboxylai- Group stands 5 ι 2
Furthermore, R and R together with the carbon atom to which they are bonded form a mono- or polycyclic ring containing at least one carbonyl group, in which the oxygen atom of the carbonyl group is replaced by a ^ N-NH-CSS-R radical can be replaced by that of the compound of the formula HTtT ft! IB fy ™ * "? _ ..TO '(^^" V \ qIS ffltl vöO Il \ XXx; 3
originates, w ~ -V "R ^ for an optionally by halogen - 64; 90 98 85/1759 ' ^J ^^^ m ■ -SAD Atoms or straight or branched "" Alky! Groups, mono- or polysubstituted straight or branched alkyl, alkenyl or aralkyl-ty groups, <> .-.-. thereby geke η η ζ et eh η et that one et / an oxo compound of the formula R ^ -CO-R ² (II) with a DittiiO carbazin acid eoter of the formula " H ₂ N ^ Ml-GSS-R ³ (111) displaced ,,
b / an oxo compound of the formula. R -'- CO-R ² ■; (III with a dithiocarbamine salt from Poruiel H ₂ N-NU-GSS-Z, (IV) - wherein ζ an alkali metal, an earth metal, an ammonium or Hydraziiniiim Ration means - lets react ■ - and in the compound of formula obtained B ¹ : ■ '■' ■ '■■ ^: - ■ ^: "" ^ C = B-SH-CSS-Z. (7) the substituents Z dureli a (troop R in well-known In the manner of sub-substituted _9: it has a hydrazone of the formula (TI) with an alkali metal * Kartriumamid or and the obtained compound of the form ©! BATH ORIGINAL C = H-HH-Z ₁ ■ ".. (VII) - wherein Z ₁ denotes a sodium or potassium atom - reacts with carbon disulfide and the compound of the formula obtained ao 'C = B-NH-OSS-Z ₁ (»») ■ , 2. · 3 by replacing the suoatituents Z ₁ with the group H converted into the corresponding compound of formula I, a requirement of the formula - worliT Z ^ for a sodium ¹ - or potassium afcom gfeehir - with a; ChlordithloaHielgefläure «ster of the formula (VIII) veraetz ^ fe, ^ e / a connection diei? Poiaael G ^ IHfH-Z ₁ (VII) -wherein Z ₁ for * a sodium or callumatoitt s-teh-t / - with thiophosgene amaeuKzii and the derivative of the formula obtained R ^{1 6} ~ 909885/1759 BATH ORIGINAL ■ * 'Ί-93Α809 with a merfcaptid of the formula R ³ -iJ-Z (I) - where Z is an alkali metal, an earth metal is an ammonium or hydrazinium means cation - allows to react, f / an H.ydrazone of the formula C = H-HH ₂ (VI) with a compound of the formula ⁴ R ⁴ (XI - where R is an alkyl or aralkyl group crosslinked at a temperature of 15 ° C 2. The method according to Anopruch 1 »characterized that at least one compound of the formulas (II) and (IV) in egg tu, prepared in the reaction mixture will. 909885/1759 3.j compounds of the formula. * v_ ■ ■ ■ Λ O-IC-HH-OBS-H ³ (I) in which. R * for hydrogen ♦ an optionally by alkoxy, carboxy » Carboxylate, carbalkoxy, or amino, alkyl! Amino. Dialkylamino and trialkylamino groups, baw. straight or branched alkyl, alkenyl, aralkyl and substituted by the pharmaceutically acceptable acidic addition salts Araikenyl group, if necessary mono- or poly-substituted ) tuierte Pheny! group, in which the substituents are the same or are different, and between halogen, alkyl »alkoxy, aoyl, Hydroxy, carboxy, carboxylate, sulfonic acid or carbalkoxy mean, an optionally mono- or polysubstituted heterocyclic group »a.B. Pyridyl, indolyl, quinolyl, Thienyl or furyl, in which the substituents are the same or are different, and indeed halogen, alkyl, alkoxy, acyl, Hydroxy, carboxy, carboxylate, sulfonic acid or carbalkoxy mean and R for hydrogen, optionally one of the definition of R , according to specified substituted straight or branched alkyl or aralkyl group »tine carboxy or carboxylate Group stands, »12 · furthermore, R and R can be taken together with the carbon atom to which they are bound a mono- or polycyclic, form at least one ring containing carbonyl groups, wherein the oxygen atom of the Oarb, onyl group by a »H ^ RH-CSS-R residue can be replaced by the compound of the formula H ₂ N-HH-OSS-R ³ (III) where R ^{J represents} an optionally substituted by halogen - 60 - 909885/1759 BATH ORIGINAL Atoms or straight or branched alkyl groups mono- or polysubstituted straight or branched alkyl, alkenyl or aralkyl group. 4. Pharmaceutical products as active ingredients at least a compound of the formula R ¹ . R ² CN-NH-OSS-R ³ (I) 12 3 contained in which ΈΓ _t R and R have the above meaning. BATH