Method for the synthesis of 9,10-bis(chloromethyl)anthracene

Abstract

The invention relates to a method for the synthesis of 9,10-bis(chloromethyl) anthracene, comprising the mixing of the reagents, anthracene and 1,3,5-trioxane, a phase transfer catalyst selected from the group comprising quarternary ammonium salt and crown ether with hydrochloric acid and acetic acid.

Claims

1. A method for the synthesis of 9,10-bis(chloromethyl)anthracene comprising: mixing the reagents containing anthracene and 1,3,5-trioxane, a phase transfer catalyst selected from the group consisting of quarternary ammonium salt and crown ether with hydrochloric acid and acetic acid.

2. The method according to claim 1, characterised in that the concentration of the phase transfer catalyst is between 1 and 5 mol %.

3. The method according to claim 1 or 2, characterised in that the molar ratio of 1,3,5-trioxane:anthracene is between 0.5 and 3.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1. 400 MHz proton NMR spectrum in deuterated chloroform and at room temperature of 9,10-bis(chloromethyl)anthracene.

DESCRIPTION OF THE EMBODIMENTS

(2) Reagents Used

(3) The reagents used in the method for the synthesis were used based on the commercial compound without purification or enrichment thereof before the synthesis.

(4) The reagents anthracene (Anthracene ReagentPlus, 99%, commercial code 141062-25G, 56.00 , Spain), acetic acid (Acetic acid ReagentPlus, 99%, commercial code A-6283-1 L, 43.60 , Spain) and 1,3,5-trioxane (1,3,5-trioxane, 99%, commercial code T81108-100G, 23.30 , Spain) were acquired from Sigma-Aldrich. The hydrochloric acid (Hydrochloric acid reagent grade, 37%, 1 L, 28.23 ) was supplied by Scharlab. Lastly, the hexadecyltrimethylammonium bromide (Hexadecyltrimethylammonium bromide, 96%, commercial code 52370-100G, 32.00 , Spain) is from Fluka.

(5) ##STR00002##

Method for the Synthesis of 9,10-bis(chloromethyl)anthracene

(6) In general, the experimental method can be described as follows: the solid reagents (anthracene, 1,3,5-trioxane and hexadecyltrimethylammonium bromide as a catalyst) are placed in a round flask without an established order of priority. Firstly, the hydrochloric acid is added to the mixture, then the acetic acid, all at room temperature and under constant and vigorous stirring (1500 rpm). Then, the mixture is exposed to different temperatures in order for the reaction to take place during a specific period of time, wherein the medium becomes a yellow colour and has a powdery appearance, without dissolving the solid present. After a fixed reaction time, the content of the flask is filtered in order to collect the yellow precipitate and it is thoroughly washed with water to eliminate the remains of trioxane, catalyst and acid species present in the medium. As a final step, the obtained solid is washed with ethanol to remove the remains of water from the washing and it is left to stove dry at 70 C. for 2 hours until completely dry.

(7) Several reaction protocols have been tested with different values for reaction temperature, time and excess of 1,3,5-trioxane as a source of formaldehyde with respect to the limiting amount of anthracene.

(8) Examples 1-4 describe the different methods for the synthesis of 9,10-bis(chloromethyl)anthracene that were tested.

Example 1. Method for the Synthesis of 9,10-bis(chloromethyl)anthracene

(9) ##STR00003##

(10) Description of Reagent Amounts Used:

(11) Anthracene 500 mg, 2.8 mmol.

(12) 1,3,5-trioxane 504 mg, 2 eq (5.6 mmol).

(13) Hexadecyltrimethylammonium bromide 25 mg, 0.07 mmol (2.5 mol %)

(14) Hydrochloric acid 37% 10 ml

(15) Acetic acid 99% 2.5 ml

(16) Reaction yield: 89%

Example 2. Method for the Synthesis of 9,10-bis(chloromethyl)anthracene

(17) ##STR00004##

(18) Description of Reagent Amounts Used:

(19) Anthracene 500 mg, 2.8 mmol.

(20) 1,3,5-trioxane 504 mg, 2 eq (5.6 mmol).

(21) Molar ratio 1,3,5-trioxane:anthracene: 2

(22) Hexadecyltrimethylammonium bromide 25 mg, 0.07 mmol (2.5 mol %)

(23) Hydrochloric acid 37% 10 ml

(24) Acetic acid 99% 2.5 ml

(25) Reaction yield: 96%.

Example 3. Method for the Synthesis of 9,10-bis(chloromethyl)anthracene

(26) ##STR00005##

(27) Description of Reagent Amounts Used:

(28) Anthracene 500 mg, 2.8 mmol.

(29) 1,3,5-trioxane 504 mg, 2 eq (5.6 mmol).

(30) Molar ratio 1,3,5-trioxane:anthracene: 2

(31) Hexadecyltrimethylammonium bromide 25 mg, 0.07 mmol (2.5 mol %)

(32) Hydrochloric acid 37% 10 mi

(33) Acetic acid 99% 2.5 mi

(34) Reaction yield: 93%.

Example 4. Method for the Synthesis of 9,10-bis(chloromethyl)anthracene

(35) ##STR00006##

(36) Description of reagent amounts used: Anthracene 500 mg, 2.8 mmol.

(37) 1,3,5-trioxane 504 mg, 1 eq (2.8 mmol).

(38) Molar ratio 1,3,5-trioxane:anthracene: 1

(39) Hexadecyltrimethylammonium bromide 25 mg, 0.07 mmol (2.5 mol %)

(40) Hydrochloric acid 37% 10 ml

(41) Acetic acid 99% 2.5 ml

(42) Reaction yield: 97% of solid that does not correspond through NMR analysis with pure product, but rather there is presence of unreacted anthracene.

(43) Below, Table 1 shows an informative table summarising the above results based on the variables.

(44) TABLE-US-00001 TABLE 1 Example Example Example Example Example Variables 1 2 3 4 5 Time (h) 24 24 14 24 24 Temperature ( C.) 100 60 60 60 25 Molar ratio 1,3,5- 2 2 2 2 1 trioxane:anthracene Yield by weight (%) 89 96 93 97 74

(45) The 9,10-bis(chloromethyl)anthracene synthesised in Examples 1-4 was characterised through proton nuclear magnetic resonance (NMR) experiments in a Bruker 400 MHz NMR, carrying out the measurements at room temperature and using deuterated chloroform (CDCl.sub.3) as a solvent in the analysis.

(46) FIG. 1 shows the 400 MHz proton NMR spectrum in deuterated chloroform and at room temperature. This spectrum is identical for the compound obtained in Examples 1-4. The spectrum coincides with the spectrum described in the state of the art (H400 MHz, CDCl.sub.3: 5.77 ppm, singlet, 4H; 7.74-7.77 ppm, multiplet, 4H; 8.53-8.55 ppm, multiplet, 4H).

Example 5. Method for the Synthesis of 9,10-bis(chloromethyl)anthracene 15

(47) ##STR00007##

(48) Description of Reagent Amounts Used:

(49) Anthracene 500 mg, 2.8 mmol.

(50) 1,3,5-trioxane 504 mg, 2 eq (5.6 mmol).

(51) Molar ratio 1,3,5-trioxane:anthracene: 2

(52) Hexadecyltrimethylammonium bromide 25 mg, 0.07 mmol (2.5 mol %)

(53) Hydrochloric acid 37% 10 ml

(54) Acetic acid 99% 2.5 mi Reaction yield: 74% of solid.

Example 6. Method for the Synthesis of 9,10-bis(chloromethyl)anthracene

(55) In this example, the following phase transfer catalysts were used:

(56) Tetrabutylammonium bromide

(57) Tetrabutylammonium fluoride

(58) Tetrabutylammonium nitrate

(59) Tetrabutylammonium hexafluorophosphate

(60) Tetrabutylammonium perchlorate

(61) Benzyl trimethylammonium chloride

(62) 4-carboxybenzyl-18-crown-6 (1,4,7,10,13,16-Hexaoxacyclooctadecane 1,4,7,10,13,16-Hexaoxacyclooctadecane) crown ether 18-crown-6 (carboxylic acid 18-2,3,5,6,8,9,11,12,14,15-decahydrobenzo[b][1,4,7,10,13,16]hexaoxacyclooctadecane 2,3,5,6,8,9,11,12,14,15-decahydrobenzo[b][1,4,7,10,13,16]hexaoxacyclooctadecane-18-carboxylic acid) crown ether

(63) Table 2 shows the reaction parameters and yield obtained in the experiments of this example:

(64) TABLE-US-00002 TABLE 2 Phase transfer Reaction time (h)/ Yield by weight catalyst used temperature ( C.) of pure product (%) Tetrabutylammonium 24/60 83 bromide Tetrabutylammonium 24/60 80 fluoride Tetrabutylammonium 24/60 71 nitrate Tetrabutylammonium 24/60 70 hexafluorophosphate Tetrabutylammonium 24/60 75 perchlorate Benzyl 24/60 70 trimethylammonium chloride 4-carboxybenzyl-18- 24/60 67 crown-6 crown ether 18-crown-6 crown ether 24/60 63