Syntheses of 7-substituted anthra[2,3- b ]thiophene derivatives and naph-tho[2,3- b :6,7- b' ]dithiophene

: 7- R - anthra[2,3- b ]thiophene derivatives ( 1 , R = H, Me, i -Pr, MeO) are prepared in three steps (in average overall yield >50%) starting from ( E )-4-RC 6 H 4 CH 2 (HOCH 2 )C=CI(CH 2 OH). The latter are commercial or readily prepared from 2-butyne-1,4-diol and ArCH 2 Cl (both costing <1 cent/mmol) at 10 g scales. These allow selective formation of (otherwise unattainable) higher solubility 7-derivatives. Similar methods allow preparation of naph-tho[2,3- b :6,7- b' ]dithiophene 2 using equally low cost starting materials.


Scheme 3. Consise methodology for synthesis of anthra[2,3-b]thiophenes (1a-d)
One of the advantages of Scheme 4 is the greater solubility of the 7-alkyl derivatives 1b-d, allowing routine acquisition of fully assigned 13 C NMR spectra, while 1b-d are also easier to process in subsequent further functionalization or device preparations. Soluble diols 12a-d can be purified either using column chromatography to yield (70-90%) or can be attained as analytically pure colorless needles by recrystallization with hot acetonitrile and cooling to 4 °C.
Optimization of Scheme 4 revealed interesting observations relevant to the scope and limitations of each of its steps (Schemes 4-6). Attempts to use the regio-isomeric Negishi reagent 14 with iodide 10b provided only low yields of 15 (32%) (Scheme 4). Extensive catalyst deactivation is observed in these reactions (see Experimental Section and Scheme 4).
Relatively few examples of 2-thienylmethyl organometallics are present in the primary literature; 24,25 with these sometimes being implicated as thermo-labile species. The appearance of multiple 1:1 signals in the range H 5.0 -6.4 in the crude spectra of 15 (assigned to =CH2 units) is in accord with anti-elimination of 14 and subsequent decomposition of the potentially derived reactive putative allene intermediate A. Compound 11, however, behaves cleanly. Interestingly regio-isomeric alcohols 12b and 15 also show different behavior upon their oxidation.
While 15 cleanly provides 16 under our preferred aerobic oxidation conditions 19 (Scheme 5) initial tests of 12b led to complex mixtures under Stahl-catalysis. 26 Similar issues were seen on attempted use of MnO2 and PCC oxidants. From these complicated mixtures the only isolable product is 17 based on spectroscopic data (Scheme 5), indicating that chemoselective oxidation is not attained. Fortunately, this issue could be overcome by simply increasing the DMSO content of Swern-based oxidations used in general conversions of 12 to 13. Scheme 4. Lower stability of (thien-2-ylmethyl)zinc(II) chloride (14)

Scheme 5. Comparative oxidation of diols 15 and 1b
The final Bradsher closure 19,20 of step of Scheme 4 easily affords 1a-d in good yields (73-99%) as bright yellow powders. These reactions show typical Friedel-Crafts behavior: at shorter reactions times mono closure onto just the electron-rich thiophene unit is observed. Thus, the scope of the final step in Scheme 4 is limited to the preparation of electron-rich anthra [2,3-b]thiophenes 1. In support of this idea closure of 13 to 1 where R = F was not achieved. The other steps of Scheme 4 are tolerant of alkyl, aryl, OR, F and Br substituents. 19 In contrast to anthra [2,3-b]thiophenes 1, previous literature syntheses of naphtho[2,3-b:6,7-b']dithiophene 2, are limited to a single route. 9,27 Commercial 2,6-dihydroxynaphthalene ($80 for 5 g 16 ) 18, is brominated to afford 1,3,5,7-tetrabromonaphthalene-2,6-diol 19 by known procedures. 28,29 Unfortunately, the literature yields for this process are reported to be highly variable (4-51%), additionally, a further four steps are required to convert 19 to 2.
We considered alternative preparation of 2 based on Negishi coupling of the diiodide 20 19 (derived from low cost 2-butyne-1,4-diol, Scheme 6). Although the yield of 21 was modest (30%), due to competing transmetallationelimination, the butyne diol by-product produced is insoluble and very simply and easily separated. The remaining steps of the sequence all give good yields and involve chromatography-free work-up procedures. Alternative procedures via the 3-thienyl analogue of 10 were investigated but were not as successful due to lower yields (see Experimental Section).

Scheme 6. Straightforward synthesis of naphtho[2,3-b:6,7-b']dithiophene (2)
Preparation of 2 was confirmed by HRMS together with 1 H, 13 C, IR and UV-vis spectroscopy. Using the latter the optical bandgaps (Eg) of 1a-d and 2 were measured using standard Tauc plots (Table 1). Hall effect studies suggested the carrier mobilities of our samples of 1-2 were less than 0.1 m 2 V -1 s -1 . In conclusion, we have established new approaches for the efficient synthesis of 7-substituted anthra[2,3-b]thiophenes 1a-d and the unsubstituted naphtho[2,3-b:6,7-b']dithiophene 2. The methods employed are simple, use low cost starting materials, and which are scalable, avoiding chromatography in many cases. These methods also offer simple flexible approaches to the inclusion of 7-substituted thiophene-acenes 1 that cannot be prepared by existing approaches. Finally, in our approach compounds 1a-d are prepared in three steps in average overall yields of >50%. Existing reported methods require four steps to attain key intermediates 3 and 4, both in ca. 30% overall yield. Final reduction of 3 is high yielding but requires toxic HgCl2. Conversely Al(O-c-C6H11)3 reduction of 4, although environmentally benign, proceeds in modest 59% yield. The approaches herein constitute useful cleaner and sustainable alternatives to these important classes of organic electronic fragments. The formation of bulk thermoelectric devices based on derivatives of 1-2 is the subject of our own future work.
Preparation of starting materials, 2-(Chloromethyl)thiophene: To a solution of thien-2-ylmethanol (10.0 g, 87.6 mmol) in dry dichloromethane (350 mL) at 0 °C, thionyl chloride (SOCl2, 12.8 mL, 45.2 mmol) was slowly added over ca. 6 min at 0 °C. The mixture was stirred for 10 minutes at 0 °C and then stirring was continued over 20 hours at room temperature. The mixture was poured on to ice, the dichloromethane was separated, and the remaining aqueous layer re-extracted with dichloromethane (3 × 70 mL). The combined organics were dried (MgSO4) and The solvent was removed under reduced pressure to give the crude 2-(chloromethyl)thiophene as a brown oil ( (Thien-2-ylmethyl)zinc(II) chloride (14): Zinc dust (<10 μm, 0.23 g, 3.57 mmol) was dried under vacuum at (0.5 mbar) at >200 °C (3-5 min), then cooled to room temperature under an atmosphere of argon. Dry tetrahydrofuran (3.0 mL) was then added, forming a grey suspension. The reaction mixture was cooled to 0 °C and trimethylsilyl chloride (12 μL, 95 μmol, 0.04 equiv) was added in one portion and the mixture stirred (30 min). Freshly distilled 2-(chloromethyl)thiophene (316 mg, 2.38 mmol) was added over 10 min. After addition the mixture was stirred at 0 ºC (5 h). A turbid white suspension (which normally titrated at >0.54 M, >74% yield) resulted over the remaining residual zinc powder. The supernatant solution could be stored for up to one week at 4 °C (resulting in clear or pale yellow supernatants), but typically the organometallic was used within 24 has attained.

3-(Chloromethyl)thiophene:
To a solution of 3-thienylmethanol (4.57 g, 40.0 mmol) in dry dichloromethane (160 mL) at 0 °C, thionyl chloride (SOCl2, 5.85 mL, 80.1 mmol) was added slowly. The mixture was stirred for 10 minutes at 0 ºC and the mixture allowed to warm to room temperature over 16 hours. The mixture was poured on to ice and the dichloromethane separated and the remaining aqueous layer re-extracted with dichloromethane (3 × 70) mL and dried (MgSO4). The solvent was removed under reduced pressure to give crude 3-(chloromethyl)thiophene as a brown oil. (Thienyl-3-ylmethyl)zinc(II) chloride (11): A dry, argon-flushed Schlenk flask equipped with a magnetic stirrer and a septum was charged with zinc dust <10 μm, (2.50 g, 38.7 mmol, 2.0 equiv). The flask was heated for 5 min under high vacuum (<0.5 mbar) using a heat gun. After cooling to 25 °C, the flask was flushed again with argon and dry THF (21.5 mL) was added and forming a grey suspension. The mixture was cooled to 0 °C and trimethylsilyl chloride (98.6 μL, 0.77 mmol, 0.04 equiv) added in one portion. The mixture allowed to stir for (35 min) at 25 °C. Freshly distilled 3-(chloromethyl)thiophene (2.57 g, 19.4 mmol) was added slowly (over 5 min) at 25 °C. (Note: equivalent results were attained using crude 3-(chloromethyl)thiophene dried overnight at rt with calcium hydride instead of distillation). After addition of the 3-(chloromethyl)thiophene was complete the mixture was warmed to 40 °C and stirred (4 h). When titrated with iodine the reaction assayed at 80%, 0.64 M. This solution could be stored at 4 °C for at least five days but was usually used as attained.
(Thienyl-3-ylmethyl)magnesium chloride: Magnesium metal (3.66 g, 150 mmol) was activated by stirring at rt overnight under argon. Anhydrous THF (50 mL) was added followed by 3-(chloromethyl)thiophene (9.24 g, 69.7 mmol), added dropwise over (16 h) using a syringe pump. The black solution when titrated with iodine indicated the desired Grignard reagent (1.77 M, 88%). The solution was used immediately to the next step. This reagent has only been described in passing in the literature. 33

Preparation of starting diols (10a-e), representative example: (Z)-2-iodo-3-(4-isopropylbenzyl)but-2-ene-1,4-diol (10c):
A solution of (4-isopropylbenzyl)magnesium chloride (39 mL, 1.1 M tetrahydrofuran solution, 42.9 mmol) was added to a stirred solution of 2-butyne-1,4-diol (1.10 g, 12.9 mmol) in dry tetrahydrofuran (23 mL) at 0 o C to form a colorless precipitate within a grey solution. The reaction mixture was allowed to warm to room temperature and stirred for 5 mins. Solid cuprous bromide dimethyl sulfide (52.9 mg, 0.26 mmol, 2 mol% based on diol) was added subsequently, against an argon flow, and the reaction mixture quickly transferred to pre-equilibrated oil bath at 60-65 o C. After 1 h at 60-65 o C the solid had dissolved forming a dark solution which was cooled first to 25 o C and then to -60 o C in a lightly lagged bath (that would allow warming from -60 to 0 o C over ca. 2 h). Solid I2 (4.35 g, 17.2 mmol) was added, against an argon flow, and the brown mixture stirred as it came to 0 o C over (2 h (17): Prepared serendipitously (but reproducibly) using a modified 2 procedure of Stahl, 26 in initial attempts to prepare (13b). Diol (12b) (0.57 g, 1.97 mmol) was dissolved in DMF (11.5 mL) without any O2 flowing. The following were promptly added to the reaction mixture sequentially: