DD275681A1 - PROCESS FOR PREPARING SUBSTITUTED N, N'-BIS (THIAZOLE-2-YL) ALKYLENEDIAMINES - Google Patents

Abstract

The invention relates to a process for the preparation of substituted N, N-bis (thiazol-2-yl) -alkylenediamines and relates to the field of organic synthetic chemistry. It has a process for the purpose of substituting substituted N, N-bis (thiazol-2-yl) -alkylenediamines of the general formula III in which R 1 is an aryl radical and R 2 and R 3 are alkyl radicals and n is 2, 3 or 4 can be made from easily accessible starting materials. Type III compounds can be used as organic intermediates. The invention has for its object to produce such N, N-bis (thiazol-2-yl) -alkylenediamines from a-thiocyanatoacetophenones. The object is achieved according to the invention in that a-thiocyanato-acetophenones of the formula I in which R 1 is an aryl radical, with alkylenediamines of the formula II in which R 2 and R 3 are identical, different or linked together alkyl radicals and n is 2, 3 or 4 may be reacted in the presence of a weak acid in solvents such as lower alcohols, halogenated hydrocarbons or dipolar aprotic solvents while applying temperatures up to the boiling point of the reaction mixture.

Description

Halogenated hydrocarbons, ζ. As methylene chloride, chloroform or carbon tetrachloride or suitable dipolar aprotic solvents, eg. For example, acetonitrile or dimethylformamide, used and applies temperatures up to the boiling point of the reaction mixture. As schwaclw acids are carboxylic acids, eg. As acetic acid, propionic acid or benzoic acid, while strong acids, eg. As perchloric acid, or the sole use'ing the alkylenediamines lead to greatly reduced yields or the complete absence of Thiazolbildung.

The resulting in the reaction substituted N, N'-bis (thiazol-2-yl) -alkylenediamino III differ when working with alcohols as a solvent in crystalline form and thus eich thus allow easy isolation (variant A, see Example 1). Working in acetonitrile or dimethylformamide (reaction temperature 90-100 ⁰ C), the crystallization of the Reektionsproduktes is initiated by addition of water. When using halogenated hydrocarbons as reaction medium, the resulting reaction mixture is mixed with water and the amines III are recovered by concentrating the organic phase (variant B, embodiment 2)

 The invention is explained below with reference to two exemplary embodiments in the form of general working instructions.

Aulführungsbeispiele

example 1

Substituted N, N'-bis (thiazol-2-yl) -alkylenediamino III by reacting a-thiocyanato-acetophenones I with alkylenediamines II in lower alcohols or dipolar aprotic solvents (general procedure, variant A, see Table 1)

It is heated lOmmol α-thiocyanato-acetophenone 1.5mmol alkylenediamine II and 10mmol acid component in 10ml of the respective solvent 2h. refluxing (DMF: reaction temperature 90-100 ° C). The thiazolyamines III which precipitate by cooling the reaction mixture, optionally with portionwise addition of water, are filtered off with suction and recrystallized from ethanol / acetone.

Example 2

Substituted N, N'-bis (th'azol-2-yl) -alkylenediamines III by reacting α-thiocyanato-acetophenones I with alkylenediamines II in halogenated hydrocarbons (general procedure, variant B, see Table 1) 10 mmol a-thlocyanoto Acetophenone 1.5 mmol of alkylenediamine II and 10 mmol of acid component are refluxed in 10 ml of halohydrocarbon for 2 hours. After cooling, the reaction mixture is treated with water, the organic phase separated and the aqueous phase extracted twice with the halogenated hydrocarbon used for the reaction. After washing the organic solutions twice with water, it is dried over sodium sulfate, the solvent i. Vak. and brings the remaining residue by treatment with ethanol for crystallization. The cleaning is carried out analogously to Example 1.

Tab. 1: Yields and melting points of the N, N'-bis (thiazol-2-yl) -alkylenediamines prepared according to the exemplary embodiments

Verb. R ¹ R ^{2 RJ} η acid component solvent Y. ¹¹ Mp. (HX) (%) ( ⁰ o purple Ph ivie me 2 acetic acid ethanol 47 157-158 methanol 44 acetonitrile 25 Dimethylformamide ²¹ 12 methylene chloride 17 chloroform 26 Carbon tetrachloride 12 * propionic ethanol 49 benzoic acid ethanol 57 IIIb 4-Me-C ₈ H ₄ me me 2 acetic acid ethanol 39 150-151 Never 4-Et-C ₈ H ₄ me me 2 acetic acid ethanol 39 113-114 IIId 4-Pr'-C ₈ H ₄ me me 2 acetic acid ethanol 25 133-134 UIE 4-Bu'-C ₈ H ₄ me me 2 acetic acid ethanol 46 185-186 HIF 4-CI-C ₈ H ₄ me me 2 acetic acid ethanol 42 169-170 IHG 4-Br-C ₈ H ₄ me me 2 acetic acid ethanol 48 175-176 IHH 4-OjN-C ₈ H ₄ me me 2 acetic acid ethanol 66 257-269 HII 2,4-Me ₂ -C ₈ H ₃ me me 2 acetic acid ethanol 66 120-121 Hij 2,4-CI ₂ -C ₈ Hj me me 2 acetic acid ethanol 35 179-180 spoof 3,4-CI ₂ -C ₈ H ₃ me me 2 acetic acid ethanol 22 178-179 HII Ph et et 2 acetic acid ethanol 18 150-152 HDouble Ph - (CH ₂ J ₂ - 2 acetic acid ethanol 49 177-179 down Ph me M * 3 acetic acid ethanol 64 146-148 IHO 4-CI-C ₈ H ₄ me me 3 acetic acid ethanol 41 106-107 IIIP 2,4-CI ₂ -C ₈ H ₃ Mo me 4 acetic acid ethanol 45 145-147 HiQ 3,4-CI ₂ -C ₈ H ₃ me me 4 acetic acid ethanol 38 ' 133-134

1 The yields refer to «I on the raw products.

2 reaction temperature 90'C.

FormlMtt "Χ.

S-CN

R ² NH (CH ₂ I _n NHR ³ (-2HX)

NC-S '

-2HX

-2H ₂ O

R ¹

N U

R ¹

R ² R ³

Claims (1)

-1- 275 6ß1 claim: Process for the preparation of substituted N, N'-bis (thiazol-2-yl) alkylene diol. In which R ^{1 is} an aryl radical R ² and R ^{3 is} identical, different or mutually linked alkyl radicals and η can be 2,3 or 4, characterized in that a-thiocyanatoacetophenones of the formula I in which R ^{1 represents} an aryl radical, with alkylenediamines of the formula II in which R ² and R ³ denote identical, different or mutually linked alkyl radicals and η can assume the values 2,3 or 4, in the presence of a weak acid, for. As acetic acid, propionic acid or benzoic acid, in solvents such as lower alcohols, for example methanol or ethanol, halogenated hydrocarbons, eg. As methylene chloride, chloroform or carbon tetrachloride or dipolar aprotic solvents, eg. For example, acetonitrile or dimethylformamide, while applying temperatures up to the boiling point of the reaction mixture. For this 1 page formulas Field of application of the invention The invention relates to a process for the preparation of substituted N, N'-bis (thiazol-2-yl) -alkylenediamines of general formula III in which R 'is an aryl radical, R ² and R ^{3 are} alkyl radicals and η is 2,3 or 4 assumptions can. Due to the possibility of modification of the aryl radicals, the thiazole system and the alkylenediamine, compounds of this type can be used as organic intermediates. Characteristic of the known technical solutions Substituted N, N'-bis (thlazol-2-yl) -alkylenediamines of general formula III in which R ¹ , R ² , R ³ and η have the abovementioned meaning are not known (cf.: RHWILEY, DCENGLAND and LCBEHR, Org. Reactions 6 (1951) 376; JMSPRAGUE and AH LAND: in: Heterocyclic Compounds (Ed. RC ELDERFIELD], Vol. 5, New York: John Wilsy and Sons, Inc., London: Chapmann and Hill, Limited, {957 , 484; The Chemistry of Heterocyclic Compounds, Vol. 34, Part "1-3, Thiazoles and its Derivatives" (Ed. JVMETZGER), New York, Chichester, Brisbane, Toronto: 1979; F. KURZER: in Organic Compounds of Sulfur, Selenium and Tellurium (Hrspb. DHREID) London: The Chemical Society, Vol. 1 (1970), p.378; 8d.2 [1973 |, p.587; Bd.3 (1975), p.566; B IDON and PALOWE, ibid., Vol.4 (1977), p.356; vol.5 Γ979], p.358, M.DAVIS, ibid., Vol.6 (1981), p.271, J.METZGER: in : Comprehensive Heterocyclic Chemistry (Ed. AR KATRITZKY, CW REES], Oxford, New York, Toronto, Sydney, Paris, Frankfurt: Pergamon Press 1984, Vol. P. 235; Chem. AbsX Vol. 1 (1907) - Vol 108 (1988) Vol 24. From a structural point of view, compounds of the type III represent 2-dialkylamino-substituted 4-aryl-hydroxides Cyclization of Suitable Acyclic Precursors (α-halo-acetophenones and Ν, Ν-Dlalkylthloureas (HANTZSCH Synthesis), see TN BIRKINSHAW, DW GILLON, SH HARKIN, GD MEAKIUS and MCTIREL, J. Chem Soc, Perkin Trans. 11984, 147; alkln-i-yl thlocyanates and dialkylamines.s.RLPDE YONG, J. MEIJER, RSSUKHAI and L.BRANDSMA, Reel.Trav. ChIm. Pays-Bas 101 [1982] 310; benzoyl thioureas and haloacetates, s. G.SEYBOLD, DE OS 3227329 (Chem Abstr 10011984] 122768); a-mercapto-acetophenones and dialkyl-cyanamides, see MD BROWN, DW GILLON, GD MEAKINS and GH WHITHAM, J. Chem. Soc., Chem 1982, 444), the ring transformation of heterocycles (dithlollum or oxathiolium salts, see K. HIRAI, H. SUGIMOTO and T. ISHIBA, Sulfur Reports 3 (1983) 1; 5,6-dihydro-thi azolol2,3-b] thiazolium salts, s. H.OHTSUKA, H.TOYOFUKU, T.MIYASAKA and K. AiUKAWA, Chem. Pharm. Bull. 23 (1975) 3234) as well as to substitution reactions on the already preformed thiazole system (2-chlorothiazoles, see R. BOSSHARD, JCMUELLER and E Ebert, DE OS 2130981 [Chem. Abstr. 76 {1972} 85806], Thiazolin-2-thiones, see S.ÖCHEITHAUER and H. Hartmann, DD WP 63374 [Chem. Abstr. 70 {1969} 77979], Z Chem. 8 (1968) 181), are also not known, and these processes would also expose the presence of specially substituted starting materials , which are usually accessible only by material and / or time-consuming synthesis steps. Object of the invention The aim of the invention is to produce easily accessible starting materials on procedurally uncomplicated catfish N, N'-bis (thlazol-2-yl) -alkylenediamine, which in the 4-position on the thiazole an aryl radical and on the amine nitrogen atoms by two , three or four methylene groups are linked together, carry alkyl radicals. Explanation of the essence of the invention The invention is based on the object, K, N'-bis (thlazol-2-yl) -alkylenedlamines of the general formula III, where R ¹ = aryl, R ² , R ³ = alkyl and η = 2,3,4 from a To produce thiocyanato-acetophenones. The object of the invention is achieved by reacting α-thiocyanato-acetophenones of the formula I in which R ^{1 is} an aryl radical with alkylenediamines of the formula II in which R ² and R ³ denote identical, different or mutually linked alkyl radicals and η can assume the values 2,3 or 4, in the presence of a weak acid and thereby reacting as solvent lower alcohols, for. Methanol or ethanol,