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Chloro–formyl steroids as precursors for hybrid heterosteroids: synthesis, spectroscopic characterization, and molecular and supramolecular structures
Author(s) -
Almagro Luis,
Nogueras Manuel,
Suárez Margarita,
Cobo Justo,
Glidewell Christopher
Publication year - 2018
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229618015887
Subject(s) - chemistry , ring (chemistry) , crystal structure , stereochemistry , nuclear magnetic resonance spectroscopy , medicinal chemistry , crystallography , organic chemistry
Two new functionalized steroids containing both chloro and formyl substituents in ring A , and intended as precursors for the synthesis of hybrid systems, have been synthesized from ketosteroid precursors. 3‐Chloro‐2‐formyl‐17,17‐dimethyl‐18‐nor‐5α‐androstane‐2,13‐diene, (I), and methyl 3‐chloro‐4‐formyl‐12‐oxo‐5β‐cholan‐3‐ene‐24‐oate, C 26 H 37 ClO 4 , (IV), have been synthesized using Vilsmeier reactions with 17β‐hydroxy‐17α‐methyl‐5α‐androstan‐3‐one and methyl 3,13‐dioxo‐5β‐cholan‐24‐oate, respectively. These products have been fully characterized using IR spectroscopy, 1 H and 13 C NMR spectroscopy, and high‐resolution mass spectrometry, and in the case of (IV), a single‐crystal X‐ray diffraction study. Crystal structures have also been determined for the known analogues 3‐chloro‐2‐formyl‐17‐oxo‐5α‐androst‐2‐ene, C 20 H 27 ClO 2 , (II), 3‐chloro‐2‐formyl‐5α‐cholest‐2‐ene, C 28 H 45 ClO, (III), and the absolute and relative configurations are assigned for all four compounds (I)–(IV): when the fusion between rings A and B is trans , 3‐chloro‐2‐formyl products are formed, but when this ring fusion is cis , a 3‐chloro‐4‐formyl product results. The formation of (I) involves not only chloroformylation at ring A , but also dehydration and the 1,2 migration of a methyl group at ring D . In each of (II), (III) and (IV), rings B and C adopt almost perfect chair conformations, while ring A adopts a half‐chair conformation. Ring D adopts an envelope conformation in each of (II) and (III), albeit differently folded in the two compounds, while in (IV), it adopts a half‐chair conformation. A single C—H…O hydrogen bond links the molecules of (II) into C (6) chains which are linked into sheets by means of carbonyl–carbonyl interactions. The molecules of (IV) are linked into simple C (7) chains, again by a single C—H…O hydrogen bond, but there are no direction‐specific interactions in (III) that are structurally significant.