Download PDF
Synthesis 2010(3): 395-397  
DOI: 10.1055/s-0029-1218593
SHORTPAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel One-Pot Synthesis of Different Derivatives of Tetraarylterephthal­aldehyde via a Multiple Aryne Sequence

Fatemeh Jabbari*, Akbar Saednya
Faculty of Chemistry, University of Tabriz, Tabriz, Iran
Fax: +98(411)340191; e-Mail: f_jabary3055@yahoo.com;

Further Information

Publication History

Received 2 October 2009
Publication Date:
07 December 2009 (online)

 PDF Download Permissions and Reprints All articles of this category

Abstract

The synthesis of a novel series of tetraarylterephthalaldehyde derivatives in an one-pot reaction is described. In this methodology 1,2,4,5-tetrachloro-3,6-diiodobenzene is treated with various aryl Grignard reagents (excess) in tetrahydrofuran to give tetraarylbenzene-1,4-diylbis(magnesium bromides). After reaction of this product with ethyl formate and aqueous quench, tetraarylterephthalaldehydes are isolated in 33-80% yields. A mechanism involving organometallic aryne intermediates is proposed.

Key words

tetraarylterephthalaldehyde - 1,2,4,5-tetrachloro-3,6-diiodobenzene - aryl Grignard reagents - tetraarylbenzene-1,4-diylbis(magnesium bromide) - ethyl formate

Tetraarylterephthalaldehydes are polyaromatic hydrocarbons that may be of interest in the fields of liquid crystals, chiral cyclophanes, benzimidazolophanes, and pharmaceuticals. [¹] [²]

In 1949 Schonberg and Alyismail [³] reported the first synthesis of 1,2,4,5-tetraphenylbenzene from the reaction of chalcone with oxalyl chloride. Breslow and co-workers [4] later showed that the reduction of the diphenylcyclopropenyl cation with zinc produced bis(diphenylcyclopropenyl), which when heated to 135 ˚C gave 1,2,4,5-tetraphenylbenzene and 1,2,3,4-tetraphenylbenzene in a ratio of 10:1.

A further method for the preparation of these compounds was reported in 1969 by Bestmann and Denzel; [5] it used the decarboxylation of 2,3-diphenylcycloprop-2-enecarboxylic acid to give 1,2,4,5-tetraphenylbenzene in 92% yield. Various methods have been used by Dodson and Fan, [6] Hoyt and co-workers, [7] Weiss and co-workers, [8] and Di Vona and Rosnati [9] in low yields. Tetraarylbenzene derivatives can be synthesized by organometallic reactions. In 1969, Berry and Wakefield treated [¹0] hexabromobenzene with magnesium in tetrahydrofuran using 1,2-dibromo­ethane as the promoter to give pentabromophenylmagnesium bromide in 32% yield. Later, it was shown that this conversion could be greatly improved using exchange with phenyl- or ethylmagnesium bromide. [¹¹] Hart and co-workers obtained [¹²] good yields of 1,2,4,5-tetraphenylbenzene from the reaction of 1,2,4,5-tetrabromo-3,6-dichlorobenzene with excess phenylmagnesium bromide and using tetrahydrofuran as the solvent; other 1,2,4,5-tetraarylbenzene derivatives were synthesized by this route. Saednya and Hart reported [¹] two efficient routes for the synthesis of m-terphenyls from 1,3-dichlorobenzene. In the first route, 2,6-dichlorophenyllithium reacted with aryl Grignard reagents to give m-terphenyls in 57-93% yield. In the second route, the reaction of 1,3-dichlorobenzene with excess aryllithium in diethyl ether at room temperature gave the corresponding m-terphenyls in 59-94% yields.

In this work we investigated the reaction of aryl Grignard reagents with 1,2,4,5-tetrachloro-3,6-diiodobenzene (1). We reasoned that 1 would undergo halogen-metal exchange preferentially at iodine to give Grignard 2. When 2 was treated with ethyl formate and then aqueous quench, tetraarylterephthalaldehydes 3-10 were obtained in good yields (Table  [¹] ).

This new synthesis has the following unique features: (1) these compounds are synthesized for first time; (2) six aryl-aryl bonds are formed in a one-pot reaction; (3) the reaction proceeds via a four-aryne sequence; (4) different aryl Grignard reagents are used to generate and trap arynes; (5) substituents are easily incorporated on the central ring; (6) the yield of the reaction is good; and (7) simple and available starting materials are used.

The essence of our method is to use a Grignard reagent to generate an aryne through metal-halogen exchange and then to trap it by nucleophilic addition. The Grignard reagent is therefore used in excess. Addition of 1,2,4,5-tetrachloro-3,6-diiodobenzene (1) in tetrahydrofuran to phenylmagnesium bromide in the same solvent under reflux conditions, followed by stirring for 15 hours gave, after treatment with ethyl formate and then hydrolysis, tetraphenylterephthalaldehyde (3) in 46% yield.

Hence, it is clear that the principle reaction product from 1 and excess phenylmagnesium bromide is tetraphenylbenzene-1,4-diylbis(magnesium bromide) (2, Ar = Ph). The reaction of this product with ethyl formate and hydrolysis with water under mild acidic condition, gave the desired product 3 in 46% yield. Other aryl Grignard reagents gave analogous products 4-10, as summarized in Table  [¹] . All of the products in Table  [¹] are new compounds. Their structures are confirmed by ¹H and ¹³C NMR and IR spectra, and elemental analysis. In general, the yields of tetraarylterephthalaldehydes are good, the only poor example being 10 which was obtained in 33% yield (entry 8).

Table 1 Synthesis of Tetraarylterephthalaldehydes

Entry Ar Product Yield (%) Mp (˚C)
1 Ph  3 46  340-341
2 4-MeC6H4  4 61  317-319
3 4-MeOC6H4  5 50  270-273
4 4-FC6H4  6 62  312-313
5 4-ClC6H4  7 a 80 >360
6 3-MeOC6H4  8 40  205
7 3-MeC6H4  9 68  246-247
8 4-PhC6H4 10 33  366-367
a The condition of this reaction was stirring at room temperature for 48 h.

The mechanism involves as key intermediates the 1,4-di-Grignard reagent 12 and various organometallic arynes as outlined for 1,2,4,5-tetrachloro-3,6-diiodobenzene in Scheme  [¹] . Rapid formation of 11 from 1 and arylmagnesium bromide is well established. Grignard exchange and elimination is then repeated to give aryne 17, which is trapped to give the di-Grignard 18. The mechanism shows that the major Grignard exchange occurs at iodine not at chlorine, and di-Grignard formation is essential to the tetraarylation reaction. Addition of arylmagnesium bromide to the intermediate organometallic arynes (i.e., 13, 17, etc.) occurs regiospecifically always to give 1,4-di-Grignards­ and not 1,3-di-Grignards.

Scheme 1

In conclusion, we have found 1 to be a useful tetraaryne equivalent that reacts with excess Grignard reagent to give tetraaryl di-Grignards 18. With subsequent addition of ethyl formate and then hydrolysis, tetraarylterephthalaldehydes 3-10 can easily be obtained from simple precursors in one step.

¹H and ¹³C NMR spectra were recorded at 400 MHz and 100 MHz, respectively, on a Bruker-Avance spectrometer using CDCl3 as a solvent and TMS as an internal standard. Melting points were determined with an Electrothermal 9100 apparatus and are uncorrected. FT-IR spectra were obtained on a Bruker-Tensor 27 spectrophotometer using KBr pellets. Elemental analysis was recorded on CHN-Rapid-Hearus apparatus. Anhyd Na2SO4 was the drying reagent throughout. Chromatography used silica gel 230-400 mesh. TLC was carried out using pre-coated plates of Merck silica gel 60 F254. All reactions were performed under dry argon using reaction vessels previously dried at 120 ˚C. THF and Et2O were distilled from benzophenone sodium ketyl prior to use.

1,2,4,5-Tetrachloro-3,6-diiodobenzene (1)

A soln of 1,2,4,5-tetrachlorobenzene (10.79 g, 49.95 mmol) and I2 (27.9 g, 110 mmol) in oleum (29% SO3, 40 mL) was vigorously stirred (magnetic) at 60 ˚C for 3.5 h. The mixture was poured into ice water and neutralized with 10% aq Na2CO3 and then 10% aq NaHCO3 and washed with 10% aq sodium bisulfite to remove excess I2. After extraction with THF and Et2O, the combined organic layers were dried (Na2SO4). Removal of the solvent gave 1 (10.03 g, 43%) as a white solid; mp 208-209 ˚C.

Tetraphenylterephthalaldehyde (3); Typical Procedure

A soln of 1 (2.4 g, 5 mmol) in anhyd THF (40 mL) was added slowly over 2 h to a soln of PhMgBr [prepared from PhBr (3.2 mL, 30 mmol), and Mg (1 g, 40 mmol) in THF (40 mL)] and the mixture was stirred for an additional 15 h at reflux. The reaction was quenched with ice and it was treated with ethyl formate (10 mL). It was then cooled in an ice-water bath and quenched with dil HCl. The aqueous mixture was extracted with THF-Et2O. The combined organic layers were dried and the solvent evaporated under reduced pressure. Recrystallization of the residue (Et2O) gave nearly pure 3 (46% yield); mp 340-341 ˚C.

FT-IR (KBr): 2843, 2741, 1699, 700 cm-¹.

¹H NMR: δ = 9.73 (s, 2 H), 7.20-7.14 (m, 12 H), 7.05-7.01 (m, 8 H).

¹³C NMR: δ = 193.8, 141.9, 137.7, 136.4, 130.5, 127.6, 127.2.

Anal. Calcd for C32H22O2: C, 87.6; H, 5.0. Found: C, 87.5; H, 5.3.

Tetra(4-tolyl)terephthalaldehyde (4)

Mp 317-319 ˚C.

FT-IR (KBr): 2846, 2735, 1704 cm-¹.

¹H NMR: δ = 9.68 (s, 2 H), 6.97 (d, J = 7.8 Hz, 8 H), 6.89 (d, J = 8 Hz, 8 H), 2.26 (s, 12 H).

¹³C NMR: δ = 194.3, 141.5, 138.3, 136.6, 133.5, 130.4, 128.3, 21.2.

Anal. Calcd for C36H30O2: C, 84.4; H, 6.1. Found: C, 84.4; H, 6.2.

Tetra(4-methoxyphenyl)terephthalaldehyde (5)

Mp 270-273 ˚C.

FT-IR (KBr): 2842, 2741, 1699, 1514, 1246 cm-¹.

¹H NMR: δ = 9.70 (s, 2 H), 6.92 (d, J = 8.7 Hz, 8 H), 6.71 (d, J = 8.7 Hz, 8 H), 3.74 (s, 12 H).

¹³C NMR: δ = 194.4, 158.5, 141.3, 138.6, 131.8, 128.7, 113.1, 55.0.

Anal. Calcd for C36H30O6: C, 77.4; H, 5.4. Found: C, 77.0; H, 5.4.

Tetra(4-fluorophenyl)terephthalaldehyde (6)

Mp 312-313 ˚C.

FT-IR (KBr): 2861, 2756, 1747, 1512, 1229 cm-¹.

¹H NMR: δ = 9.70 (s, 2 H), 7.00-6.95 (m, 8 H), 6.91 (t, J = 8.7 Hz, 8 H).

¹³C NMR: δ = 192.1, 160.9 (d, J C4-F = 246.5 Hz), 140.3, 136.9, 131.01 (d, J C2-F = 8.2 Hz), 130.8 (d, J C1-F = 3.5 Hz), 114.03 (d, J C3-F = 21.5 Hz).

MS (EI, 70 eV): m/z (%) = 44 (100), 481 (71), 510 (64), 356 (28).

Anal. Calcd for C32H18F4O2: C, 75.2; H, 3.55. Found: C, 75.2; H, 3.8.

Tetra(4-chlorophenyl)terephthalaldehyde (7)

Following the typical procedure using 1-bromo-4-chlorobenzene (25 mmol) and Mg (25 mmol) in THF (30 mL) at r.t. for 48 h. When the mixture was extracted with THF-Et2O or CH2Cl2, the product precipitated; mp >360 ˚C.

FT-IR (KBr): 2835, 2742, 1700, 1090, 806 cm-¹.

¹H NMR: δ = 9.67 (s, 2 H), 7.20 (d, J = 8.4 Hz, 8 H), 6.94 (d, J = 8.4 Hz, 8 H).

¹³C NMR: δ = 191.7, 140.1, 136.8, 133.2, 132.9, 130.6, 127.2.

Anal. Calcd for C32H18Cl4O2: C, 66.6; H, 3.1. Found: C, 65.2; H, 3.1.

Tetra(3-methoxyphenyl)terephthalaldehyde (8)

Mp 205 ˚C.

FT-IR (KBr): 2842, 2739, 1701, 1594, 1244, 1041 cm-¹.

¹H NMR: δ = 9.76 (s, 2 H), 7.18-7.07 (m, 4 H), 6.79-6.52 (m, 12 H), 3.66 (s, 6 H), 3.62 (s, 6 H).

¹³C NMR: δ = 193.7, 158.8, 141.4, 137.6, 128.6, 123.2, 116.0, 115.8, 113.3, 55.1.

Anal. Calcd for C36H30O6: C, 77.4; H, 5.4. Found: C, 77.3; H, 5.5.

Tetra(3-tolyl)terephthalaldehyde (9)

Mp 246-247 ˚C.

FT-IR (KBr): 2920, 2736, 1704, 1307, 702 cm-¹.

¹H NMR: δ = 9.67 (s, 2 H), 6.99-6.87 (m, 8 H), 6.77-6.73 (m, 8 H), 2.13 (s, 12 H).

¹³C NMR: δ = 193.03, 140.8, 136.6, 135.9, 135.6, 135.3, 130.3, 126.8, 126.6, 126.2, 20.2.

Anal. Calcd for C32H30O2: C, 84.4; H, 6.1. Found: C, 85.3; H, 6.1.

Tetra(biphenyl-4-yl)terephthalaldehyde (10)

Mp 366-367 ˚C.

FT-IR (KBr): 2923, 2852, 1698, 732 cm-¹.

¹H NMR: δ = 9.86 (s, 2 H), 7.57-7.52 (m, 8 H), 7.46 (d, J = 8.3 Hz, 8 H), 7.41 (t, J = 7.2 Hz, 8 H), 7.32(tt, J = 7.2,1.2, 2 Hz, 4 H) 7.16 (d, J = 8.3 Hz, 8 H).

¹³C NMR: δ = 193.9, 141.6, 140.2, 139.9, 131.09, 128.7, 127.4, 126.9, 126.3.

Anal. Calcd for C56H38O2: C, 90.5; H, 5.1. Found: C, 88.4; H, 6.8.

Acknowledgment

The authors are indebted to Tabriz university for supporting of this work and Mrs. Aghazadeh for her helpful suggestions during the manuscript preparation.

   Permissions and Reprints All articles of this category

Scheme 1