4-Iodonaphthalene-1-carboxylic acid synthesis

1-Naphthalenecarboxylic acid, 4-iodo-, methyl ester

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Yield:91059-41-5 86%

Reaction Conditions:

Stage #1: 1-iodo-4-methoxycarbonylnaphthalenewith potassium hydroxide in water; for 12 h;Inert atmosphere;Reflux;
Stage #2: with hydrogenchloride in water;

Steps:

5.1.6. 4-Chloro-1-naphthoic acid (22, X = Cl)

General procedure: To a solution of 2.44 g (11.9 mmol) of 1-acetyl-4-chloronaphthalene in 5 mL of freshly distilled pyridine under N₂ was added 3.33 g (13.1 mmol) of I₂ dissolved in 15 mL of freshly distilled pyridine. The mixture was heated at reflux for 40 min, cooled to ambient temperature and diluted with ether until a brown precipitate formed. The precipitate was filtered off, suspended in 12 mL of 6 M aqueous NaOH and heated at reflux for 2 h. After cooling the solution was acidified with 10% HCl, the crude 4-chloro-1-naphthoic acid was extracted into ether and the ethereal extract was washed with brine. After drying (MgSO₄) the solution was concentrated in vacuo. The product was dissolved in 25 mL of MeOH to which 5 mL of concentrated H₂SO₄ was cautiously added. The solution was heated at reflux for 3 h. After cooling to ambient temperature the crude ester was extracted into ether, the ethereal solution was washed with brine and dried (MgSO₄). The solution was concentrated in vacuo to give 1.66 g (63%) of methyl 4-chloro-1-naphthoate as a brown oil, which was used without further purification: ¹H NMR (300 MHz, CDCl₃) δ 3.90 (s, 3H), 7.38 (d, J = 7.8, 1H), 7.45-7.56 (m, 2H), 7.87 (d, J = 8.1, 1H), 8.18 (d, J = 8.4, 1H), 8.93 (d, J = 8.1, 1H); ¹³C NMR (75.5 MHz, CDCl₃) δ 52.1, 124.6, 124.9, 125.8. 126.2, 127.1, 128.3, 129.9, 130.7, 132.3, 137.2, 166.9; GC/MS (EI) m/z (rel intensity) 220 (61), 189 (100), 161 (48), 126 (42).A mixture of 0.25 g (1.1 mmol) of methyl 4-chloro-1-naphthoate and 2.10 g (37.4 mmol) of KOH in 20 mL of H₂O was heated at reflux for 12 h under N₂. The reaction mixture was cooled to ambient temperature, acidified with concentrated HCl and the product was extracted into ether and dried (MgSO₄). The organic phase was concentrated in vacuo to give 0.27 g (88%) of 4-chloro-1-naphthoic acid as an off-white solid

References:

Wiley, Jenny L.;Smith, Valerie J.;Chen, Jianhong;Martin, Billy R.;Huffman, John W. [Bioorganic and Medicinal Chemistry,2012,vol. 20,# 6,p. 2067 - 2081] Location in patent:experimental part

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