Ammonium Chloride → (Z)-2-Phenyl-4-(3,4,5-trimethoxystyryl)thiazole

HRID 522564Notes

Reaction equation

HRID 522564 reaction equation
[Li]CCCC.[Br-].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:32]=[C:33]([O:37][CH3:38])[C:34]=1[O:35][CH3:36])[CH2:12][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[C:39]1([C:45]2[S:46][CH:47]=[C:48]([CH:50]=O)[N:49]=2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[NH4+].[Cl-]>C1COCC1>[C:39]1([C:45]2[S:46][CH:47]=[C:48](/[CH:50]=[CH:12]\[C:11]3[CH:32]=[C:33]([O:37][CH3:38])[C:34]([O:35][CH3:36])=[C:9]([O:8][CH3:7])[CH:10]=3)[N:49]=2)[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 370917Triphenyl(3,4,5-trimethoxybenzyl)phosphonium bromideHCID 7365242-Phenyl-1,3-thiazole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 53363789(Z)-2-Phenyl-4-(3,4,5-trimethoxystyryl)thiazoleYield 27.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Triphenylphosphine (3.41 g, 13 mmol) was added to a solution of 5-(bromomethyl)-1,2,3-trimethoxybenzene (2.61 g, 10 mmol) in dry THF (30 mL). The mixture was refluxed with stirring for 6 h. The resulting white solid was filtered and washed with ether/hexane to afford the product 3,4,5-trimethoxybenzyltriphenylphosphonium bromide in 96.4% yield. 1H NMR (500 MHz, CDCl3) δ 7.77-7.73, 7.65-7.61 (m, 15H), 6.44 (d, 2H, J=1.5 Hz), 5.37 (d, 2H, J=14 Hz), 3.76 (s, 3H), 3.51 (d, 6H); MS (ESI) m/z 443.1 (M−Br]+. At −78° C., n-BuLi (0.42 mL, 2.5 N in hexane) was added to a solution of 3,4,5-trimethoxybenzyltriphenylphosphonium bromide (500 mg, 0.96 mmol) in 10 mL THF. After stirring at RT for 2 h, aldehyde 42b (109 mg, 0.58 mmol) in 3 mL THF was charged and stirred for 30 min. The reaction mixture was treated with saturated NH4Cl solution. After a conventional workup, column chromatography (silica gel, petroleum ether/ethyl acetate) gave compounds 3a (57 mg) and 3b (99 mg). 1H NMR (500 MHz, CDCl3) δ 7.90-7.89 (m, 2H), 7.42-7.40 (m, 3H), 7.07 (s, 1H), 6.71 (s, 2H), 6.66 (s, 1H), 3.87 (s, 6H), 3.75 (s, 3H); MS (ESI) m/z 376.1 (M+Na)+.

Workup

  1. stirringstirred for 30 min

Sources & evidence

ORD record
ord-f4fc70fbe6d34b94a3f10ebaffff38d7
Source dataset
uspto-grants-2016_05
Patent number
US09334242B2

Reaction notes

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