Hi,

 See

https://en.wikipedia.org/wiki/Rosenmund%E2%80%93von_Braun_reaction

Which thiadiazole? There are 4:

1,2,3-

1,2,4-

1,2,5-

1,3,4-

Each one might have a different answer, but the common conditions using CuCN/ DMF might give a mono substitution product.

Bill

its 4,7-dibromobenzo[c][1,2,5]thiadiazole; please see the reaction scheme also.

Dhirendra,

I would personally try along the lines of prof. Buchwald's research: Copper-Catalyzed Domino Halide Exchange-Cyanation of Aryl Bromides; J. Zanon, A. Klapars, S. L. Buchwald, J. Am. Chem. Soc., 2003, 125, 2890-2891.

You will find more on the Rosenmund-von Braun reaction in the link provided.

Regards,

Jacek

http://www.organic-chemistry.org/namedreactions/rosenmund-von-braun-reaction.shtm

Dhirendra Kumar 4,7-dibromobenzo[c][1,2,5]thiadiazole to mono CN?

 Hi,

 A problem: The CuCN route has already been tried, but the product is the DiCN compound. The procedure calls for 4 equivalents of CUCN, and a high temperature (150 deg). Maybe if you cut back on the CuCN and use a lower temp. you can get some of the mono CN product- probably mixed with the di-CN, but separable.

A couple of alternate routes are also added below.

Bill

AT14  . Property modulation of benzodithiophene-based polymers via the incorporation of a covalently bonded novel 2,1,3-benzothiadiazole-1,2,4-oxadiazole derivative in their main chain for polymer solar cells

By Agneeswari, Rajalingam; Tamilavan, Vellaiappillai; Song, Myungkwan; Hyun, Myung Ho

From Journal of Materials Chemistry C: Materials for Optical and Electronic Devices (2014), 2(40), 8515-8524.

 DI-NITRILE:

Benzo[c][1,2,5]thiadiazole-4,7-dicarbonitrile (1). To a stirred solution of 4,7-dibromobenzo[c][1,2,5]thiadiazole (7.35 g, 25 mmol) in N,N-dimethylformamide (DMF, 70 mL) was added copper cyanide (9.0 g, 100 mmol). The mixture was heated to 150 oC for 72 h and then it was cooled to room temperature (RT). The mixture was poured into 2 N HCl (200 mL) and extracted (2 x 100 mL) with ethyl acetate (EA). The combined organic layer was washed well with brine solution and then the organic layer was dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation and the crude product was purified by column chromatography (silica gel, hexane:CH2Cl2, 20/80) to afford compound 1 as a colorless solid. Yield: 2.2 g (47%). 1H NMR (300 MHz, CDCl3): d (ppm) 8.15 (s, 2H); 13C NMR (75 MHz, CDCl3): d (ppm) 152.6, 134.7, 114.1, 110.9; HRMS (EI+, m/z) [M+] calcd for C8H2N4S 186.0000, found 186.0006

 The same paper gives a six-step route to the 4-Br, 7-CN product you want.

 (Sorry no picture)  Three steps to make the 4-Me, then 4-Br,7-Me, then the 4-Br, 7-(bromomethyl), then the 4,Br, 7-CHO, and finally the 4-Br,7CN.

4-Bromo-7-methylbenzo[c][1,2,5]thiadiazole (6). Compound 6 (the 4-Br, 7-Me compound)  was prepared via the similar reported procedure. ref 31 Compound 5 (4-Me1,2,5-thiadiazole) (3.2 g, 21.3 mmol) and 48% HBr (80 mL) were stirred at RT. To this solution was added Br2 (1.20 mL, 22 mmol) in 48% HBr (80 mL) dropwise. Then, the mixture was heated to reflux for 16 h. The solution was cooled to RT and the mixture was poured into saturated sodium bisulfate solution. The mixture was stirred for 30 min and then extracted (2 x 100 mL) with CH2Cl2. The combined organic layer was dried over anhydrous Na2SO4, filtered, and then the solvent was evaporated by rotary evaporation. The crude product was purified by column chromatography (silica, hexane:EA, 90/10) to afford compound 6 as a colorless solid. Yield: 4.5 g (92%). 1H NMR (300 MHz, CDCl3): d (ppm) 7.72 (d, 1H), 7.22 (d, 1H), 2.70 (s, 3H); 13C NMR (75 MHz,

CDCl3): d (ppm) 155.4, 153.4, 132.3, 131.5, 129.1, 111.4, 17.9.

4-Bromo-7-(bromomethyl)benzo[c][1,2,5]thiadiazole (7).

Compound 7 was prepared via the similar reported procedure.31 Compound 6 (4.0 g, 17.4 mmol), N-bromosuccinimide (NBS, 3.1 g, 17.5 mmol) and benzoyl peroxide (10 mg) were dissolved in CCl4 (140 mL). The solution was heated to reflux and 33% HBr in acetic acid (1 mL) was added. After 3 h, the reaction mixture was poured into water (100 mL). The organic layer was separated and dried over anhydrous Na2SO4, filtered, and then the solvent was evaporated by rotary evaporation. The crude product was purified by column chromatography (silica, hexane:EA, 90/10) to afford compound 7 as a colorless solid. Yield: 4.5 g (92%). 1H NMR (300 MHz, CDCl3): d (ppm) 7.81 (d, 1H), 7.53 (d, 1H), 4.94 (s, 2H); 13C NMR (75 MHz, CDCl3): d (ppm) 155.4, 153.4, 132.3, 131.5, 128.8, 114.5, 27.9.

7-Bromobenzo[c][1,2,5]thiadiazole-4-carbaldehyde (8).

Compound 8 was prepared via the slightly modied procedure.32 Compound 7 (2.8 g, 9.1 mmol) and sodium periodate (NaIO4) (0.42 g, 2.3 mmol) were added in a round bottom flask and then DMF (30 mL) was added. The reaction mixture was heated at 150 oC for 3 h. Again, NaIO4 (0.42 g, 2.3 mmol) was added to the solution with continuous stirring for 2 h at 150 oC. The reaction mixture was cooled and poured into water (100 mL) and then extracted with EA (2  50 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and then the solvent was evaporated by rotary evaporation. The crude product was purified by column chromatography (silica, hexane:EA, 90/10) to afford compound 8 as a yellow colored solid. Yield: 1.2 g (54%). 1H NMR (300 MHz, CDCl3): d (ppm) 10.73 (s, 1H), 8.11 (d, 1H), 8.06 (d, 1H); 13C NMR (75 MHz, CDCl3): d (ppm) 188.6, 154.5, 152.6, 132.4, 132.0, 127.1, 122.2.

7-Bromobenzo[c][1,2,5]thiadiazole-4-carbonitrile (9).Compound 9 was prepared via a previously reported procedure.33 (i.e. LL11)

A stirred solution of compound 8 (1.0 g, 4.1 mmol) and hydroxylamine hydrochloride (0.57 g, 8.2 mmol) in DMSO (30 mL) was heated at 100 oC for 2 h. Then, the reaction mixture was cooled to RT and poured into water (100 mL). The mixture was stirred for 30 min and then allowed to settle down. The precipitates were titrated off and washed well with MeOH and hexane. The solid was dried under vacuum to afford compound 9 as a colorless solid. Yield: 0.82 g (84%). 1H NMR (300 MHz, CDCl3): d (ppm) 7.96 (d, 2H), 7.91 (d, 2H); 13C NMR (75 MHz, CDCl3): d (ppm) 153.3, 152.6, 136.1, 131.6, 121.5, 115.0, 105.6.

LL11  . New A-A-D-A-A-type electron donors for small molecule organic solar cells

By Lin, Li-Yen; Lu, Chih-Wei; Huang, Wei-Ching; Chen, Yi-Hong; Lin, Hao-Wu; Wong, Ken-Tsung

From Organic Letters (2011), 13(18), 4962-4965.

 LL11 Support

Same:

Synthesis of 4-bromo-7-cyano-2,1,3-benzothiadiazole (2). A mixture of 7-Bromo-2,1,3-benzothiadiazole-4-carbaldehyde (16.3 g, 67.1 mmol) and hydroxylamine hydrochloride (9.32 g, 134.1 mmol) in DMSO (250 mL) was stirred and heated at 100 oC for 2h. After the reaction mixture was cooled to room temperature, the resulting precipitate was collected by filtration, and the crude product was washed with MeOH and then CH2Cl2 to afford 2 as a yellow solid (12.96 g, 80%). M.p. 259-260 oC; IR (KBr) ν 3080, 3040, 2232, 1528, 1480, 1375, 1102, 1032, 942,

876 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.97-7.90 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 153.1, 152.3, 135.8, 131.4, 121.3, 114.7, 105.3. HRMS (m/z, FAB+, [M+H]+) Calcd for C7H379BrN3S 239.9231, found 239.9225, Calcd for C7H381BrN3S 241.9211, found 241.9207

Perhaps an alternate way:

The synthesis and properties of novel π-conjugated 2,1,3-benzothiadiazole oligomers

    By Xu, Erjian; Zhong, Hongliang; Du, Junping; Zeng, Danli; Ren, Shijie; Sun, Jing; Fang, Qiang

    From Dyes and Pigments (2008),  Volume Date2009, 80(1), 194-198

 .1. Synthesis of 4-bromo-7-hexyl-2,1,3-benzothiadaizole ( 2)

But Use MeI instead of hex-Br to get the 4-Br-7-Me

Under argon atmosphere, a solution of N,N-dimethylacetamide (DMAC, 20 mL), I2 (0.25 g, 1 mmol) and zinc dust (2.0 g, 31 mmol) was stirred at room temperature until the red color disappeared. Then 1-bromohexane (2.8 mL, 20 mmol) was added and the mixture was reacted at 80 oC for 4 h. After being cooled to room temperature, the obtained alkylzinc reagent was added to a mixture of 4,7-dibromo-2,1,3-benzothiadiazole (7.8 g, 27 mmol), Pd(PPh3)4 (0.57 g, 0.49 mmol) and DMAC (30 mL) at room temperature. The reactants were allowed to heat at 80 oC for overnight, and then cooled to room temperature. The mixture was poured into water, filtered and washed with water and ethanol, respectively. After evaporation of the solvent, the residue was purified by chromatography on silica gel using a mixture of petroleum ether and CH2Cl2 (6:1, v/v) as the eluent to give 2 as a colorless liquid, 3.16 g, yield of 54%. 1H NMR (CDCl3, 300 MHz, ppm): d 7.75 (d, J ¼ 7.2, 1H), 7.24 (d, J ¼ 7.2, 1H), 3.08 (t, J ¼ 8.4, 2H), 1.72–1.84 (m, 2H), 1.25–1.45 (m, 6H), 0.88 (t, J ¼ 6.9, 3H). 13C NMR (CDCl3,100 MHz, ppm): d 154.7,153.4,136.0,132.0,127.7,111.2, 32.0, 31.6, 29.6, 29.1, 22.6, 14.0. IR (KBr, cm -1): 2956, 2928, 2858, 1596, 1532, 1483, 1466, 1326, 1227, 938, 883, 842. MS (EI) m/z: 300.Elemental analysis, calculated for C12H15BrN2S: C, 48.17%; H, 5.05%; N, 9.36%; S,10.72%; Br, 26.70%. Found: C, 48.35%; H, 5.06%; N, 9.57%; S, 10.84%; Br, 26.75%

Ie, Yutaka; Jinnai, Seihou; Karakawa, Makoto; Aso, Yoshio

Chemistry Letters, 2015 ,  vol. 44,  # 5  p. 694 – 696

No Help:  Prep of Br CN refers to L.-Y. Lin, C.-W. Lu, W.-C. Huang, Y.-H. Chen, H.-W. Lin, K.-T. Wong, Org. Lett. 2011, 13, 4962. (i.e. LL11)

 One other alternate: use a Pd catalyst with Zn(CN)2:

Development of Pd/C-Catalyzed Cyanation of Aryl Halides

By Yu, Hannah et al

From Journal of Organic Chemistry, 76(2), 665-668; 2011

  The arylhalide used here is 3-Bromopyridine

            General/Typical Procedure:

 Representative experimental procedure To a round bottom flask was added aryl halide (2.9 mmol), zinc cyanide (0.21 g; 1.74 mmol; 0.6 equiv) (CAUTION: HIGHLY TOXIC1), 10 wt % Pd/C2 (0.13 g; 0.058 mmol; 2 mol %), 1, 1'-bis (diphenylphosphino)ferrocene (dppf) (66 mg; 0.116 mmol; 4 mol %) and DMAC (5 mL). The resulting slurry was sparged with sub-surface nitrogen for 10 min, and zinc formate dihydrate (46 mg; 0.29 mmol; 10 mol %) was added to the reaction mixture. The reaction mixture was again sparged with sub-surface nitrogen for 10 min, and was heated under nitrogen to 100-120 °C3. Reaction conversion was monitored by HPLC. For workup procedures used to obtain isolated yields, please refer to Section 4. Isolated with Method A with control of distillation temperature/pressure to avoid loss of product. Input 3-bromopyridine: 2.0 g (theoretical output 1.32 g); output: 1.16 g (88% yield). pyridine-3-carbonitrile 1H NMR (400 MHz, CDCl3) δ ppm 8.92 (1 H, s), 8.84 (1 H, d, J = 4.8 Hz), 8.00 (1 H, d, J = 8.0 Hz), 7.47 (1 H, dd, J = 8.0 Hz, J = 5.2 Hz). 13C NMR (400 MHz, CDCl3) δ ppm 153.0, 152.5, 139.3, 123.7, 116.5, 110.1. Anal. calcd for C6H4N2 C, 69.22, H, 3.87, N, 26.91, found C, 69.36, H, 3.88, N, 26.82.

Dhirendra,

I have just found the Buchwald paper (attached, you can find SI online). Based on the type of conditions and stoichiometry involved, it promises a reasonable yield of mono-nitrile in 1 step, in case you use 1.2 equiv NaCN (maybe it makes sense to try a lower temperature first). I would be surprised if this does not work.

Prof William Frost Berkowitz and Prof Jacek Martynow Sir

thanks a lot for your valuable suggestions. Actually, whatever Prof William Frost Berkowitz suggested, I am aware of that procedure, but I just want to ignore such long synthetic procedure. In that case, the net yield to synthesize the final product will become low only when compare to a single step. But, I am also looking a clean method.