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Efficient M edium-Scale Synthesis o f 2-Bromo-5-te/-f-butylbenzene- 1,3-dicarbaldehydeM arco H. Klingele and Berthold Kersting*Institut für Anorganische und Analytische Chemie der Albert-Ludwigs-Universität, Albertstraße 21, D-79104 Freiburg, Germany

Reprint requests to Dr. B. Kersting.Fax: +49 (0)761 203 5987.E-mail: kerstber@uni-freiburg.de

Z. Naturforsch. 56b, 437-439 (2001); received December 27, 2000

2-Bromo-5-rert-butylbenzene-l,3-dicarbaldehyde, Benzene Derivatives

A short and efficient multi-gram synthesis of the title compound has been designed which al­lows its preparation from commercially available material in only three steps in overall yields of60-70% .

IntroductionTransition m etal complexes featuring central

M(w2-SR)nM (M = metal, n = 1 -3 ) core units have been the subject of intensive research in recent years due to their intriguing electronic and m ag­netic properties [1,2] as well as to their occurrence in biological systems [3-5]. Some of the latest w ork in our group has been concerned with the synthesis, characterization and property studies of dinuclear first-row transition m etal complexes of acyclic [6 -9 ] and macrocyclic [10] amine-thiophe- nolate ligands. The required ligands have been prepared by the condensation of aromatic alde­hydes with a,a»-diamines followed by reduction of the resulting imines. This approach, which is based on the original strategy by Robson et al. [11], is versatile and has been used for the synthesis of a large num ber of ligand systems [12-20]. In our ligand syntheses, 2-bromo-5-terr-butylbenzene-l,3- dicarbaldehyde (4) has served as the arom atic head unit which undergoes facile substitution reac­tions with thiols at room tem perature in N,N-d\- m ethylform am ide in the presence of potassium carbonate. This allows the introduction of thi- o e ther functions under very mild conditions. Sub­sequent deprotection with sodium in liquid am m o­nia liberates the corresponding thiophenols and hence affords the polydentate am ine-thiopheno- late ligands. Dialdehyde 4 was unknown when we

first got involved in this type of chem istry so it was necessary to design a synthesis which would give easy access to sufficient am ounts of this com ­pound. The interest of others [21] in dialdehyde 4 has prom pted us to report our h itherto unpub­lished synthesis.

ResultsC heap 5-ferr-butyl-l,3-dim ethylbenzene (1) was

treated with brom ine and a catalytic am ount of iron pow der in te trachlorom ethane solution at 0 °C [22]. To prevent light-induced radical side-re­actions this reaction was carried out in a flask w rapped with tin foil. Thus, known brom ide 2 was obtained in nearly quantitative yield upon w ork­up. Subsequent benzylic oxidation was achieved with chrom ium (V I) oxide and conc. sulfuric acid in acetic anhydride. This step was somewhat te ­dious and required care since the reaction was very exotherm ic. Chrom ium (V I) oxide dissolved only slowly in acetic anhydride and the resulting solutions appeared to be unstable above 30 °C. Therefore the required am ount of oxidizing agent was split up in several portions and only small am ounts were prepared and added at one time. According to this protocol 3 was obtained in yields of up to 75%. Finally, 3 was hydrolyzed with conc. sulfuric acid and w ater in m ethanol to give 4 in alm ost quantitative yield. In summary, dialdehyde4 was prepared from commercially available 5-tert- butyl-1,3-dim ethylbenzene (1) in only three steps in overall yields of 6 0 -7 0 % .

ExperimentalCaution: C hrom ium (V I) oxide is a powerful oxi­

dizing agent and should be handled with great care. Solutions of chrom ium (V I) oxide in acetic anhydride readily oxidize organic m atter in very exotherm ic reactions.

4-tert-Butyl-2,6-dimethylbromobenzene (2)To a solution of 5-tert-butyl-l,3-dim ethylben-

zene (1) (89.3 g, 0.56 mol) in tetrachlorom ethane (60 ml) was added iron pow der (3.1 g, 10 m ol-% ). A solution of brom ine (87.9 g, 0.56 mol) in te tra ­chlorom ethane (30 ml) was added dropwise at 0 °C in the dark during a period of 2 h. A fter com ­plete addition, the resulting m ixture was stirred at room tem perature for 12 h protected from light. The reaction m ixture was then washed with sat. aqueous sodium thiosulfate (100 ml), 2 M aqueous

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438 Notizen

Br, cat. Fe, Cr03, conc. H2S04,— -------► -------------------►CCI4, 0°C Ac20 , <10 °C

conc. H2S 0 4, H20,-------------------- ►

MeOH, 0 °C

sodium hydroxide (3 x 50 ml) and w ater (3 x 50 ml) and dried over anhydrous magnesium sul­fate. Evaporation of the solvent gave 126.5 g (95% ) of crude 2 as a colorless oil which crystal­lized on standing. Recrystallization from ethanol gave analytically pure m aterial as colorless n ee­dles. - M.p. 47 -4 9 °C. - 'H N M R (200 MHz, CDCI3): (3 = 1.26 (s, 9 H, A rC (C //3)3), 2.40 (s, 6H, A rC //3), 7.02 (s, 2 H , A rH). - 13C{'H) N M R (50 MHz, CDC13): <5 = 24.0, 31.3, 34.3, 124.4, 125.4,137.6, 149.6. - C 12H 17Br (241.17): calcd. C 59.76, H 7.10; found C 59.35, H 7.31.

I,3-Bis(diacetoxymethyl)-2-bromo-5-tert- butylbenzene (3)

To a suspension of 2 (96.5 g, 0.40 mol) in acetic anhydride (800 ml) was added conc. sulfuric acid (120 ml) dropwise at such a rate as to m aintain the tem perature below 10 °C. To the resulting mixture was added a solution of chrom ium (V I) oxide (140.0 g, 1.40 mol) in acetic anhydride (700 ml) dropwise while the tem perature was kept below10 °C. Since solutions of chrom ium (V I) oxide in acetic anhydride appear to be unstable above 30 °C, the oxidizing agent was prepared and added in five separate portions. A fter com plete addition, the green suspension was stirred for further 2 h below 10 °C. The resulting mixture was poured onto ice (8000 ml) portionwise with efficient stir­ring. A fter standing at room tem perature for 12 h, the precipitate was filtered off and washed th o r­oughly with water. Drying in vacuo gave 138.4 g (73% ) of crude 3 as a yellowish solid. Recrystalli­zation from ethanol gave analytically pure m ater­

ial as colorless plates. - M.p. 151-153 °C. - !H NM R (200 MHz, CDC13): (3 = 1.35 (s, 9 H, A rC (C //3)3), 2.16 (s, 12 H , C O C //3), 7.61 (s, 2 H, A r//) , 7.97 (s, 2 H, A r CH). - 13C{’H} N M R (50 MHz, CDC13): (3 = 20.5, 30.9, 34.9, 88.9, 119.5,126.1, 135.2, 151.1, 168.1. - C20H 25B rO 8 (473.32): calcd. C 50.75, H 5.32; found C 50.68, H 5.15.

2-Bromo-5-tert-butylbenzene-l,3-dicarbaldehyde(4)

To a suspension of 3 (104.1 g, 0.22 mol) in m eth ­anol (500 ml) was added conc. sulfuric acid (1100 ml) dropwise at 0 °C. A fter com plete addi­tion, the resulting orange solution was stirred at room tem perature for 1 h. U pon dropwise addi­tion of w ater (2000 ml) at 0 °C, the product precip­itated from the solution. It was filtered off and washed thoroughly with water. Drying in vacuo gave 57.5 g (97% ) of crude 4 as a pale yellow solid. Crystallization from dichlorom ethane/cyclohexane gave analytically pure m aterial as a colorless crys­talline solid. - M.p. 85 -8 7 °C. - !H N M R (200 MHz, CDC13): (3 = 1.36 (s, 9 H, A rC (C //3)3), 8.16 (s, 2 H, A r //) , 10.54 (s, 2 H , ArC/ZO). - 13C{!H} NM R (50 MHz, CDC13): (5 = 30.7, 34.8, 127.9,132.3, 133.9, 151.8, 190.7. - C 12H 13B r 0 2 (269.14): calcd. C 53.55, H 4.87; found C 53.24, H 5.01.

AcknowledgmentsThis work was supported by the D eutsche

Forschungsgemeinschaft. The authors thank Prof.H. Vahrenkam p for his generous support. Techni­cal assistance from Mr. C. M attes is also g ra te­fully acknowledged.

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