What is the meaning of [2,1-c][1,4] in pyrrolo[2,1-c][1,4]benzodiazepine?

Question

Pyrrolobenzodiazepines are a group of DNA-alkylating natural products. What is the exact meaning of the [2,1-c][1,4] part in the full descriptive name pyrrolo[2,1-c][1,4]benzodiazepine?

![Pyrrolo2,1-c][1,4]benzodiazepine

General structure of pyrrolo[2,1-c][1,4]benzodiazepines. The 2-3 double bond is not present in all natural products.

Thanks to Loong I may be able to figure it out.

1,4-Benzodiazepine is pretty trivial, as [1,4] defines the position of the nitrogens like this:

For clarification [1,5] could look like 1H-1,5-benzodiazepine:

[2,1-c] is answered in What does the "h" "k" and "(5.2.2.02,6)" mean in dibenzo(h,k)-4-oxatricyclo(5.2.2.02,6)undec-8,10- diene-3, 5-dione?

According to the current version of Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013 (Blue Book), isomers of fused polycyclic ring systems are distinguished by lettering each peripheral side of the parent component using the italic letters a, b, c, etc., beginning with a for the side numbered ‘1,2’, b for ‘2,3’, etc.

So the letters would be:

So pyrrolo[2,1-c] would be attached to the c-side. I still need clarification in one point though:

Does the direction 2,1 (NOT 1,2) show the direction of the attachment?

Answer 1

Yes, the order of the numbers indicates the relative orientation of the fused ring system. The direction of the numbers of the attached component (e.g. ‘1,2’ or ‘2,1’) corresponds to the direction of the lettering of the parent component (i.e. a, b, c, etc.).

For example:

The correspondig Subsection P-25.3.1.3 in the current version of Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013 (Blue Book), reads as follows:

(…)
Isomers are distinguished by lettering, continuously, each peripheral side of the parent component (…) using the italic letters a, b, c, etc., beginning with a for the side numbered ‘1,2’, b for ‘2,3’ etc. To the letter as early in the alphabet as possible that denotes the side where the fusion occurs are prefixed, if necessary, the numbers of the positions of attachment of the other component. These numbers are chosen to be as low as is consistent with the numbering of the compound and their order conforms to the direction of lettering of the parent component. (…)