DE2262471C3 - Process for the preparation of 2-substituted thiazoles - Google Patents

Description

where R has the above meaning,
characterized in that the dehydrogenating agent used is chloranil, 2,3-dichloro-5,6-dicyanobenzoquinone or benzoquinone

The compounds of the general formula
-N

where R is the isopropyl or the isobutyl radical, have interesting flavor properties. That's how it is Compound I with R = isobutyl (2-isobutyl-thiazoI) as Tomato flavor has become known (see Viani et al, HeIv. Chim. Acta, 52,887-891 [1969], Buttery et al., J. Agr. Food Chem., 19,524-529 [1971], Kazemiac et al., J. of Food Science, 519-530 [197O]). The compound I with R = isopropyl (2-isopropyl-thiazole) is from Cottet et al .. Bull. Soc. Chim. France, 4502-4507 (1967) and by Vernin et al, BuII. Soc. Chim. France, 846-855 (1967). has been described. Their taste is sweeter and potato-like.

No economical production processes have yet become known for these two compounds. From Liebigs Ann. Chem .. 610 (1957), 49 -56 is known that Δ 'thiazolines with an alkyl or phenyl can be at least slightly in the 4-abutment condition dehydrate to give the corresponding thiazoles, wherein ais particularly suitable dehydrogenating agent, sulfur is specified. As our own experiments have shown, the Δ behave '-thiazolines the formula II

where R has the above meaning,
Completely different from sulfur in that strong resinification occurs and therefore only slight bulges on the desired thiazoles I can be achieved. With other dehydrogenating agents mentioned in DE-AS 10 29 826 only low yields were obtained.

Contrary to expectations, it has now been found that have the <d ³ -thiazolines of formula II with chloranil, 2 _r 3-log chloro-5,6-dicyano-benzoquinone or benzoquinone dehydrate in excellent yields to the thiazoles of general formula I .

The subject matter of the invention is accordingly the method characterized by the claim.

ίο The dehydration according to the invention can be in the presence or in the absence of a solvent. It is preferred in a solvent worked. Examples of suitable solvents are: ethers, such as diethyl ether, dioxane, aliphatic Hydrocarbons such as pentane, hexane, alicyclic hydrocarbons such as cyclohexane; aromatic solvents, such as benzene, toluene, xylene, halogenated hydrocarbons such as chloroform, dichloromethane. It is preferred to work in aromatic solvents.

The molar quantitative ratio of the compound II to the quinone is expediently about 1: 1, but there is also an excess, e.g. B. of 150%, quinone into consideration.

The reaction temperature is expediently between about room temperature and the reflux temperature the solution. A temperature range from about 80 to about 120 ° C. is preferred.

The reaction time depends on the quinone used and

jo depends on the reaction temperature. Are z. B. chloranil and benzene used as solvents, the reaction time is approx. 30 minutes to approx. 2 hours.

The isolation of the reaction product can according to

ii known methods take place, e.g. B. by narrowing of the reaction mixture, taking up the thiazole in ether, washing this solution with lye, drying and fractional distillation after evaporation of the solvent.

Serving as starting materials for the process according to the invention, the compounds of the general Formula II can be obtained by methods known per se by using isobutyraldehyde or isovaleraldehyde is reacted with ammonia or an ammonium salt and oc-mercaptoacetaldehyde.

In the following examples the temperatures are in Degrees Celsius.

in example!

26, u g (0.186 mol) of 2-isobutyl'-thia / olin are in 400 ml abs. Benzene dissolved. 45.6 g (0.186 mol) of chloranil are added to this solution and the mixture is reverberated

γ, refluxed for 40 minutes. The main amount of benzene is distilled off at normal pressure and the residue is mixed with 500 ml of 2N sodium hydroxide solution / l. Extract! six times with 1 50 ml of ether each time. The combined, organic phases are then over anhydrous

dried bo sodium sulfate and the solvent is distilled off at normal pressure. By fractional distillation of the higher-boiling residue over a VigreuX'Kolönne you get 16.98 g (60% dent) Gaschiomalographically uniform ^ -IsobuiyNthiazol

6 ·> with the bp. 59-60Vl 2 mm Hg; / ?? = 1.4947.

lR'Spektfum (liq.): bands Ua at 3100, 2970, 1500, 1460, 1170,! 150, 1045, 720 cm- ¹ . NMR spectrum (CDCh): (5 7.22 (d, (= 3.5 Hz; 1H); 7.20 (d, (= 3.5 Hz;

99 fi9 4-71

IH); 2 ^ 3 (d, J = 7 Hz; 2 H); 2.15 (septet, J = 7 Hz; 1H); 1.01 (d, J = 6.5 Hz; 6 H) ppm; Mass spectrum: inter alia m / e 141 (M ⁺ ) (3%), 126 (10%), 99 (100%), 58 (53%).

The 2-isobutyM ¹ -thiazoline used as starting material can be obtained as follows:

In a mixture of 52 g (0.34 mol) of dimeric α-mercaptoacetaldehyde (M. Thiel, F. Asinger, K. Schmiedel Ann., 611 [1958], 126). 97 g (!, 13 mol) of isovaleraldehyde and 30 g of anhydrous sodium sulfate in 200 ml of ether are slowly passed in ammonia gas with stirring at 20 ° for 20 minutes. Thereafter, the reaction mixture is heated to 60 ° and ammonia gas is passed through for a further 10 minutes. The mixture is filtered off from the sodium sulfate, washed twice with 20 ml of ether each time and the solvent is distilled off at normal pressure through a column. Fractional distillation of the (higher-boiling) residue over a Vigreux column gives 53.5 g (55% yield, based on the α-mercaptoacetaldehyde used), 2-isobuiv! - / l ³ -thiazoline which is uniform by gas chromatography and has a boiling point of 73-74 ° / 8 Torr, / !? = 1.4956:

IR spectrum (Hq.): Bands inter alia at 1640, 1465 cm- '; Nuclear Magnetic Resonance Spectrum (CDCl ₃ ): <5 7.42 (m, 1 H), 5.69 (m, 1 H) ₁ 3.92 (m, 2 H), 2.12-1.38 (m, 3 H), 1.01 (m, 6 H) ppm; Mass spectrum: including m / e 143 (M ⁺ ) (38%), 128 (16.3%), 110 (75%), 96 (57%), 86 (100%).

Example 2

From 13.11 g (0.1015 mol) of 2-isopropyl-4 ^:) -thiazoIin and 25 g (0.1015 mol) of chloranil, 7.44 g (7% yield) are obtained by gas chromatography, according to the procedure of Example 1 I-thiaz ^ i with the bp. 44-45V12 mm Hg and / Jf = 1.4839 obtained.

IR spectrum (liq.): Bands at 3 "H), 2980, 1500, 1470, 1160, 1045, 1010, 720cm- '; NMR spectrum (CDCIi): δ 7.66 (d, J = 3, 5 Hz; 1 H); 7.14 (d, J = 3.5 Hz; 1 H); 3.34 (septet, J = 7 Hz; 1 H); 1.40 (d, J = 7 Hz; 6 H) ppm; mass spectrum: including m / e 126 (M ⁺ ) (32%), 112 (100%), 58 (45%).

The 2-isopropyldmhiazoline used as the starting material can be obtained as described above for the 2-isobutyl-4 ³ -thiazoline:

From 52 g (034 mol) of dimeric α-mercaptoacetaldehyde

and 81.5 g (1.13 mol) of isobutyraldehyde will be

50.1 g (57% yield, based on "mercaptoacetaldehyde") of 2-isopropyM ³ -thiazoIin with a boiling point of 60-63 ° / 9 Torr, / J ₁ - = 1.4991; IR spectrum (liq.): Bands inter alia at 1650, 1470 cm- '; Nuclear Magnetic Resonance Spectrum (CDCIj): <5 7.45 (m, 1 H), 5.62 (octet, 1 H), 3.83 (m, 2 H), 2.08 (Septettoii, 1 H), 1 .05 (d, J = 6.5 Hz, 3 H), 0.90 (d.

J = 6.5Hz, 3H), ppm; Mass spectrum: including m / e i29 (M ⁺ ) (32%), 86 (100%).

Example 3

A slurry of 2.27 g (0.01 mol) of 23-dichloro-5,6-dicyarobenzoquinone in 30 ml of absolute benzene is added to 1.43 g (0.01 mol) of 2-isobutyl-4 ^{3 -thiazoIin and that} The reaction mixture was kept at reflux temperature for 2 hours. The solvent is distilled off at normal pressure and the residue is subjected to Kugelrohr distillation, 0.948 g (67.2% yield) of 2-isobutyl-thiazol7i, '= 1, which is uniform by gas chromatography, at an oven temperature of 90-120 ° and a pressure of 20 mm Hg , 4946) which is identical to the product of Example 1 (IR, NMR, mass spectrum).

Example 4

37.5 g (0.261 MoI) i-isobutyl-4 ^J -thiazotin are dissolved together with 44.2 g (0.408 MoI) benzoquinone in 300 ml of toluene absulutem. The reaction mixture is obtained for 2½ hours in a nitrogen atmosphere at reflux temperature, and the solvent is then distilled off at normal pressure. 850 ml of 2 η sodium hydroxide solution are added to the residue and the mixture is extracted with 3 l of ether. The organic phases are washed with saturated saline

Washed neutral, combined and dried over sodium sulfate dried. The solvent is distilled off and the residue is fractionated on a Widmer column distilled.

The fraction boiling at 58-59 ° mm Hg (14.65 g

ίο colorless oil, 39.8% yield) is 2-isobutyl-thiazole (r, - = ■ 1.4965) which is uniform by gas chromatography and which is identical to the product of Example 1 in spectroscopic terms.

Claims (1)

Claim: Process for the preparation of 2-substituted thiazoles of the general formula where R is the isopropyl or isobutyl radical, by dehydrating a compound of the general formula