4-BROMOPYROLE-2-CARBOXALDEHYDE

General procedure: In a round-bottomed flask, the substrate (1 mmol) and aqueous HBr(48percent) (1 mL) were mixed in DMSO (1 mL). The mixture was stirredat corresponding temperature for 1–4 h. After cooling to roomtemperature, the reaction was adjusted to pH 7–8 with aqueous NaOHsolution (4 M). Then the mixture was washed twice with EtOAc, andthe combined organic extracts were dried, filtered and concentratedunder reduced pressure to give bromination products.4-Bromo-1 H-pyrrole-2-carboxaldehyde (41). To a stirred solution of 1 H-pyrrole-2- carboxaldehyde 40 (1 g, 10.52 mmol) in CHThe synthesis of an 8-bromo-substituted Western half is shown in Scheme 5. Treatment of pyrrole-2-carobxaldehyde with one molar equivalent of NBS at -78 °C gave 4-bromopyrrole-2-carboxaldehyde 17 (Anderson, J. H.; Lee, S.-F. Can. J. Chem. 1965, 43, 409-414) in 55percent yield after crystallization. This method of bromination of pyrrole-2-carboxaldehyde is superior to a reported method that uses BrTo a 100 mL 3-neck RB flask charged with 1H-pyrrole-2-carbaldehyde (1.0 g, 10.5 mmol) in THF(20 mL) at -78°C, NBS (1.87 g, 10.53 mmol) in THF(20 mL) was addedslowly and thenthe flaskw as maintained at the same temperature for 1 h. The reaction mixture was diluted with hexane and water mixture, the organic layer was decanted. The organic layer was dried over anhydrous Na2SO4 and then concentrated at low temperature under vacuo. It was recrystallized with n-hexane to yield the title compound (1 .0 g, 54.0percent) as a pale pink solid.1H-Pyrrole-2-carbaldehyde (20g, 210mmol) was dissolved in 250ml tetrahydrofuran and the mixture was cooled to−78°C. N-Bromosuccinimide (37g, 210mmol) was added portion-wise over 1h with stirring and the mixture was stirred for a further 6.5at−78°C. The mixture was allowed to warm to 0°C and was partitioned between water and hexane and protected from the light. The aqueous phase was extracted with cold hexane and the combined organics were washed with water, dried over anhydrous sodium sulphate and filtered. The organics were concentrated under reduced pressure until a precipitate formed. The solid was cold-filtered, washed with cold hexane and dried under vacuum to give 12.8g of 80. The filtrates were concentrated again under reduced pressure until further precipitate formed. This was collected by filtration as before and combined with the first obtained solid to give 80 (18.9g, 109mmol, 53percent yield). Purity 96percent. Stored at 4°C in the dark. 4.3.5 General procedure: To a stirred solution of 55 (2.0 g, 13.42 mmol) in THF (100 mL) was added portion- wise DBDMH (1.90 g, 6.71 mmol) in a period of 10 min at -78 C. Then the reaction mixture was stirred for 5 h while it was allowed to warm to room temperature. The reaction was quenched with 5% aqueous KHS04 solution, and extracted with ethyl acetate (3 x 75 mL). The combined organic layers were washed with brine and dried over anhydrous Na2S04. The solvent was evaporated under reduced pressure and the product was (0188) chromatographed on silica gel, with ethyl acetate/hexanes as eluent, to afford the pure product 56 (2.48 g, 82%). lH NMR (CDCI3, 400 MHz) delta 10.60 (br s, 1H), 9.41 (s, 1H), 2.83 (m, 2H), 2.42 (m, 2H), 1.77 (m, 4H); 13C NMR (CDCI3, 100 MHz) delta 175.7, 134.7, 128.9, 122.7, 110.5, 22.8, 22.6, 21.3, 21.0; HRMS (ESI) calcd for C9HnBrNO (M + H)+ 228.0019, found 228.0031A mixture of intermediate 4-bromo-lH-pyrrole-2-carbaldehyde [931-33-9] (1.41 g, 8.10 mmol), methyl-4-bromohex-2-enoate [119226-97-0] (2.26 g, 9.72 mmol, 89% purity) and potassium carbonate (2.46 g, 17.3 mmol) in DMF (38 mL) was stirred at rt for 16 h. The reaction mixture was poured out into water and the aqueous phase was extracted with EtOAc (twice). The combined organic extracts were washed with brine, dried over MgS04, filtered and the solvent was evaporated in vacuo. The crude mixture was purified by preparative LC (regular SiOH, 30 pm, 200 g Interchim, dry loading (Celite), mobile phase gradient: heptane / EtOAc from 100:0 to 50:50) to afford intermediate A1 (0.65 g, 28%).

Twenty-one halo- and cyanopyrroles related to the trail pheromone of A. texana, Methyl 4-Methylpyrrole-2-carboxylate [34402-78-3], were prepared and tested by a faster and more sensitive bioassay than was previously available. Methyl 4-Chloropyrrole-2-carboxylate [1194-96-3] and Methyl 4-bromopyrrole-2-carboxylate appeared to be as active as the first one. Responsiveness of the ants in descending order to these compounds based on the constituent in the number two position, was: esters, methyl ketones, aldehydes.

Molecular Weight:174.00
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:172.94763
Monoisotopic Mass:172.94763
Topological Polar Surface Area:32.9
Heavy Atom Count:8
Complexity:96.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes