9-Methoxynaphtho[1,2-b]benzofuran

Round 1

Reviewer 1 Report

 This paper discusses the selective synthesis of 9-methoxynaphtho[1,2-b]benzofuran by the reaction of 1-naphthol with 1-bromo-4-methoxy-2-nitrobenzene.   Although the product yield is low (30%), the complex compound is selectively synthesized as a sole product.   Thus, the reviewer feels the results should be worth publishing in this Journal.   However, there seems to be a problem in structural analysis of the product.   The authors assigned the product to the 9-methoxy isomer on the basis of HMBC measurement, but the analysis seems to be problematic.   The crossover signal at (7.27, 118.17) indicates adjacent H10 and C6-C, suggesting that such long-range coupling is unlikely.   In the HMBC measurement of aromatic compounds, 3J(C,H) (vicinal coupling) is often observed rather than 2J(C,H) (germinal coupling).   With this in mind, the structure of the product raises the question of the 8-methoxy isomer.   The reviewer recommends reconsidering the structural analysis of the product.   Thus, the reviewer recommends the major revision of the manuscript before the publication.

Author Response

The authors are very grateful to the reviewer for the time devoted to this revision, as well as for the valuable feedback and constructive comments on the manuscript. The changes introduced are currently highlighted within the new version of the manuscript. Please find below, our response to the comment.

Based on the comment about ³J(C,H) correlation of aromatic compounds, we have corrected the assignments from 119.3 (C-C7), 118.2 (C-C6) to 119.3 (C-C6), 118.2 (C-C7), in line with the ³J correlation H-10/C-C7, the latter added among the significant correlations.

The structure of the 9-methoxy isomer is unambiguously assigned relying on the following data:

• we performed a NOESY experiment (reported as Figure S6 in Supplementary), observing the significant H-6/H-7 effect. Moreover, the distance of 2.626 Å between these protons in the energy-minimized structure by MM calculations (Chem3D software, CambridgeSoft Corporation) is compatible with this NOE.
• Based on data available for both isomers [2], it was possible to observe:

7. a) that H-10 at 7.27 ppm of our compound (7.25 in reference [2]) (d, J = 2.3 Hz) is in line with an upfield value (due to the proximity of two O atoms) in comparison with the H-7 at 7.45 ppm (d, J = 2.5 Hz) reported for the 8-OMe derivative.
8. b) a perfect agreement of our ¹H and ¹3CNMR data with the ones reported for the structure of 9-OMe derivative, further confirmed by X-ray analysis on a derivative of this regioisomer [2].

Therefore, the phrase of the text “Further support was found in good agreement with the reported data, where the structure of a 9-methoxy derivative was confirmed by X-ray analysis [2]” has been more widely explained as: “Further support was found in a perfect agreement with the reported data, where the discrimination between 8-methoxy and 9-methoxy compounds was certainly achieved by X-ray analysis for a 9-methoxy derivate [2].”

Round 2

Reviewer 1 Report

 This paper discusses the selective synthesis of 9-methoxynaphtho[1,2-b]benzofuran by the reaction of 1-naphthol with 1-bromo-4-methoxy-2-nitrobenzene.   The reviewer feels the results should be worth publishing in this Journal.   The problem in the structural analysis of the product was clearly resolved by the NOE measurement.   The reviewer feels the revision was properly established by reflecting the reviewer's opinion.   The reviewer considers the revised manuscript to become suitable for publication.   Thus, the reviewer recommends publication of this paper as this version.