Expected and Unexpected Products in Half Curcuminoid Synthesis: Crystal Structures of But-3-en-2-ones and 3-Methylcyclohex-2-enones

Round 1

Reviewer 1 Report

The submitted study is concise yet very interesting. It presents some unusual behavior of solid organics. Overall impression is positive but there are some major issues, presented below, that need clarification.

Line 8, is “[email protected]” a correct address?

Line 26, it seems that abstract ends unexpectedly; please correct.

Line 41, it should be “anti-inflammatory”

Line 47, I wouldn’t call this analysis “full” as in fact only one spectroscopic technique has been used (liquid state NMR)

Scheme 1 is very nice, congratulations!

Line 109, what do you mean by “normal values”?

Table 1, I assume that Z’ for each structure was 1?

I highly appreciate the crystallographic discussion. In contrast to commonly published discussion on crystal structures the one in this study is very concise, interesting, with a suitable references, without unnecessary focus on the particular angles and lengths. Again, good work!

Compound II, do you think that it is possible to obtain the “pure” crystals of only one conformation (either trans-s-trans or trans-s-cis)? Maybe at  lower T? Do you think that this conversion between the conformations can occur in solid state as well as in the solution? Have you tried to assess the rotation barrier?

Compound III, have you tried to separate the enantiomers in order to obtain the crystals of only one stereoisomer?

I am a little bit disappointed that the Authors have not used any methods of molecular modeling, i.e. periodic DFT calculations. Those structures seem to be perfect candidates for computational studies. By doing this the Authors could have strengthen their multiple hypothesis stated in the discussion part. Please consider this option.

Author Response

Dear Reviewer 1: we greatly appreciate your valuable time and useful comments.

Author Response File: Author Response.pdf

Reviewer 2 Report

This is a very nice piece of X-ray structural work, and well presented in terms of both text and graphics. The four crystal structures have been thoroughly investigated and explained. I have only one question, which is why the R_merge is so high? In fact, they are unreasonably high. Combined with the very low number of observed reflections, something tells me that the crystals scatter very poorly, but this is not mentioned. The ratio of observed reflections to parameters is in all cases less than 10, so the authors need to give more details about the data quality.

Author Response

Dear Reviewer 2: we greatly appreciate your time and encouraging comments!

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The Authors have included my comments and corrected their manuscript accordingly. I find it now suitable for publication.