()‐3‐Oxo­cyclo­hexane­carboxyl­ic and ‐acetic acids: contrasting hydrogen‐bonding patterns in two homologous keto acids

The crystal structures for the title compounds reveal fundamentally different hydrogen‐bonding patterns. ()‐3‐Oxo­cyclo­hexanecarboxylic acid, C₇H₁₀O₃, displays acid‐to‐ketone catemers having a glide relationship for successive components of the hydrogen‐bonding chains which advance simultaneously by two cells in a and one in c [O?O = 2.683 (3) Å and O—H?O = 166°]. A pair of intermolecular close contacts exists involving the acid carbonyl group. The asymmetric unit in ()‐3‐oxo­cyclo­hexane­acetic acid, C₈H₁₂O₃, utilizes only one of two available isoenthalpic conformers and its aggregation involves mutual hydrogen bonding by centrosymmetric carboxyl dimerization [O?O = 2.648 (3) Å and O—H?O = 171°]. Intermolecular close contacts exist for both the ketone and the acid carbonyl group.     

Precursor of a β‐lactamase inhibitor: allyl (4S,8S,9R)‐10‐[(E)‐ethyl­idene]‐4‐methoxy‐11‐oxo‐1‐aza­tri­cyclo­[7.2.0.03,8]­undec‐2‐ene‐2‐carboxyl­ate

The molecular structure of the title tricyclic compound, C₁₇H₂₁NO₄, which is the immediate precursor of a potent synthetic inhibitor {Lek157: sodium (8S,9R)‐10‐[(E)‐ethyl­idene]‐4‐methoxy‐11‐oxo‐1‐aza­tri­cyclo­[7.2.0.0^3,8]­undec‐2‐ene‐2‐carboxyl­ate} with remarkable potency, provides experimental evidence for the previously modelled relative position of the fused cyclo­hexyl ring and the carbonyl group of the β‐lactam ring, which takes part in the formation of the initial tetrahedral acyl–enzyme complex. In this hydro­phobic mol­ecule, the overall geometry is influenced by C—H?O intramolecular hydrogen bonds [3.046 (4) and 3.538 (6) Å, with corresponding normalized H?O distances of 2.30 and 2.46 Å], whereas the mol­ecules are interconnected through intermolecular C—H?O hydrogen bonds [3.335 (4)–3.575 (5) Å].     

The epimeric 9‐oxobicyclo[3.3.1]nonane‐3‐carboxylic acids: hydrogen‐bonding patterns of the endo acid and the lactol of the exo acid

The two δ‐keto carboxylic acids of the title, both C₁₀H₁₄O₃, are epimeric at the site of carboxyl attachment. The endo (3α) epimer, (I), has its keto‐acid ring in a boat conformation, with the tilt of the carboxyl group creating conformational chirality. The mol­ecules form hydrogen bonds by centrosymmetric pairing of carboxyl groups across the corners of the chosen cell [O⃛O = 2.671 (2) Å and O—H⃛O = 179 (2)°]. Two close intermolecular C—H⃛O contacts exist for the ketone. The exo (3β) epimer exists in the closed ring–chain tautomeric form as the lactol, 8‐hydroxy‐9‐oxatri­cyclo­[5.3.1.0^3,8]­undecan‐10‐one, (II). The mol­ecules have conformational chirality, and the hydrogen‐bonding scheme involves intermolecular hydroxyl‐to‐carbonyl chains of mol­ecules screw‐related in b [O⃛O = 2.741 (2) Å and O—H⃛O = 177 (2)°].     

(+)‐Camphor­acetic acid: catemeric hydrogen bonding in a γ‐keto acid

The title compound, (1R)‐4,7,7‐tri­methyl‐3‐oxobi­cyclo­[2.2.1]­heptane‐2‐endo‐acetic acid, C₁₂H₁₈O₃, like its lower homolog, forms carboxyl‐to‐ketone hydrogen‐bonding catemers (Z′ = 2) [O⋯O = 2.729 (5) and 2.707 (5) Å, and O—H⋯O = 165 and 170°] with screw‐related components. The two mol­ecules of the asymmetric unit differ slightly in conformation and produce two counter‐aligned hydrogen‐bonding chains, both aligned with the b axis. Close intermolecular C—H⋯O=C contacts exist for the ketone group of one mol­ecule and for both the ketone and carboxyl functions in the other.     

2,2′‐Methyl­enebis(3‐hydroxy‐2‐cyclo­hexen‐1‐one)

In the title compound, C₁₃H₁₆O₄, the cyclo­hexene rings adopt a sofa conformation. Adjacent mol­ecules are connected by C—H?O intermolecular interactions. Each mol­ecule is characterized by O—H?O intramolecular hydrogen bonds. The anti arrangement of the enolic OH group and the carbonyl O atom in the solid state is similar to the anti arrangement of the NH and carbonyl groups in indigo.     

9,9‐Dimethoxy‐7,11‐diphenyl‐2,4‐diazaspiro[5.5]undecane‐1,3,5‐trione monohydrate

Due to steric repulsions, the cyclo­hexane ring in the title compound, C₂₃H₂₄N₂O₅·H₂O, shows some bond‐length abnormalities and adopts a chair conformation. The pyrimidine and cyclo­hexane rings are approximately perpendicular to each other, and the phenyl rings are equatorial. C—H?π and N—H?O intermolecular interactions, as well as C—H?O inter‐ and intramolecular interactions, occur between the mol­ecules. In addition to van der Waals interactions, the water mol­ecule interacts with the pyrimidine­trione ring to stabilize the structure.     

Phenyl‐ and mesitylglyoxylic acids: catemeric hydrogen bonding in two α‐keto acids

α‐Oxo­benzene­acetic (phenyl­glyoxy­lic) acid, C₈H₆O₃, adopts a transoid di­carbonyl conformation in the solid state, with the carboxyl group rotated 44.4 (1)° from the nearly planar benzoyl moiety. The heterochiral acid‐to‐ketone catemers [O?O = 2.686 (3) and H?O = 1.78 (4) Å] have a second, longer, intermolecular O—H?O contact to a carboxyl sp³ O atom [O?O = 3.274 (2) and H?O = 2.72 (4) Å], with each flat ribbon‐like chain lying in the bc plane and extending in the c direction. In α‐oxo‐2,4,6‐tri­methyl­benzene­acetic (mesityl­glyoxy­lic) acid, C₁₁H₁₂O₃, the ketone is rotated 49.1 (7)° from planarity with the aryl ring and the carboxyl group is rotated a further 31.2 (7)° from the ketone plane. The solid consists of chiral conformers of a single handedness, aggregating in hydrogen‐bonding chains whose units are related by a 3₁ screw axis, producing hydrogen‐bonding helices that extend in the c direction. The hydrogen bonding is of the acid‐to‐acid type [O?O = 2.709 (6) and H?O = 1.87 (5) Å] and does not formally involve the ketone; however, the ketone O atom in the acceptor mol­ecule has a close polar contact with the same donor carboxyl group [O?O = 3.005 (6) and H?O = 2.50 (5) Å]. This secondary hydrogen bond is probably a major factor in stabilizing the observed cisoid di­carbonyl conformation. Several intermolecular C—H?O close contacts were found for the latter compound.     

4‐Ethynyl‐4‐hydroxycyclohexan‐1‐one and 4‐ethynyl‐4‐hydroxy‐2,3,5,6‐tetramethylcyclohexa‐2,5‐dien‐1‐one

The title compounds, C₈H₁₀O₂, (I), and C₁₂H₁₄O₂, (II), occurred as by‐products in the controlled synthesis of a series of bis­(gem‐alkynols), prepared as part of an extensive study of synthon formation in simple gem‐alkynol derivatives. The two 4‐(gem‐alkynol)‐1‐ones crystallize in space group P2₁/c, (I) with Z′ = 1 and (II) with Z′ = 2. Both structures are dominated by O—H?O=C hydrogen bonds, which form simple chains in the cyclo­hexane derivative, (I), and centrosymmetric dimers, of both symmetry‐independent mol­ecules, in the cyclo­hexa‐2,5‐diene, (II). These strong synthons are further stabilized by C[triple‐bond]C—H?O=C, C_methylene—H?O(H) and C_methyl—H?O(H) interactions. The direct intermolecular interactions between donors and acceptors in the gem‐alkynol group, which characterize the bis­(gem‐alkynol) analogues of (I) and (II), are not present in the ketone derivatives studied here.     

3‐(p‐Chloro­phenyl)‐4‐phenyl‐4,5‐di­hydro­isoxazole‐5‐spiro‐2′‐1′,2′,3′,4′‐tetra­hydro­naphthalen‐1′‐one

In the title compound, C₂₄H₁₈ClNO₂, the phenyl ring and the tetralone moiety are approximately orthogonal to the isoxazoline ring. The isoxazoline ring adopts an envelope conformation, while the cyclo­hexenone ring of the tetralone moiety has an intermediate sofa/half‐chair conformation. In this structure, one C—H?N intermolecular and two C—H?O intramolecular hydrogen bonds occur; the H?A distances are 2.60, and 2.35 and 2.57 Å, respectively. The mol­ecules are held together by an intermolecular C—H?N hydrogen bond, forming a one‐dimensional chain along the [100] direction.     

A 1:1 adduct of hexa­methylene­tetramine and 4‐hydroxy‐3‐methoxy­benz­aldehyde

In the title complex, C₆H₁₂N₄·C₈H₈O₃, the hexa­methyl­ene­tetramine mol­ecule accepts a single intermolecular O—H?N hydrogen bond from the hydroxy group of the 4‐hydroxy‐3‐methoxy­benz­aldehyde moiety. The non‐centrosymmetric crystal structure is built from alternating molecular sheets of 4‐hydroxy‐3‐methoxy­benz­aldehyde and hexa­methyl­ene­tetramine mol­ecules, and is stabilized by intermolecular O—H?N, C—H?O and C—H?π interactions.     

2‐{[Tris(hydroxymethyl)methyl]aminomethylene}cyclohexa‐3,5‐dien‐1(2H)‐one and its 6‐hydroxy and 6‐methoxy derivatives

The title compounds, 2‐{[tris­(hydroxy­methyl)­methyl]­amino­methyl­ene}cyclo­hexa‐3,5‐dien‐1(2H)‐one, C₁₁H₁₅NO₄, (I), 6‐hydroxy‐2‐{[tris­(hydroxy­methyl)­methyl]­amino­methyl­ene}­cyclo­hexa‐3,5‐dien‐1(2H)‐one, C₁₁H₁₅NO₅, (II), and 6‐methoxy‐2‐{[tris­(hydroxy­methyl)­methyl]­amino­methyl­ene}­cyclo­hexa‐3,5‐dien‐1(2H)‐one, C₁₂H₁₇NO₅, (III), adopt the keto–amine tautomeric form, with the formal hydroxy H atom located on the N atom, and the NH group and oxo O atom display a strong intramolecular N—H⋯O hydrogen bond. The N—H⋯O hydrogen‐bonded rings are almost planar and coupled with the cyclo­hexa­diene rings. The carbonyl O atoms accept two other H atoms from the alcohol groups of adjacent mol­ecules in (I), and one from the alcohol and one from the phenol group in (II), but from only one alcohol H atom in (III).     

(+)‐Gibberellin C: hydrogen‐bonding pattern of the monohydrate of a non‐racemic pentacyclic diterpenoid

In the monohydrate of the title compound, (+)‐2β,4aα‐di­hydroxy‐1,7‐di­methyl‐8‐oxo‐4bβ,7α‐gibbane‐1α,10β‐di­carb­ox­yl­ic acid‐1,4a‐lactone, C₁₉H₂₄O₆·H₂O, intermolecular hydrogen bonding progresses helically along b from carboxyl to ketone [O?O = 2.694 (5) Å]. The carboxyl and lactone carbonyl groups in translationally related mol­ecules within a helix both accept hydrogen bonds from the same water of hydration. The oxy­gen of this water in turn accepts a hydrogen bond from the hydroxyl group of a third screw‐related mol­ecule in an adjacent counterdirectionally oriented helix, yielding a complex three‐dimensional hydrogen‐bonding array. Intermolecular O?H—C close contacts were found to the carboxyl and lactone carbonyls, the hydroxyl, and the water.     

3,4‐Di­hydro‐6‐methyl‐3‐β‐d‐ribo­furan­osyl‐4,5′‐cyclo‐9H‐imidazo[1,2‐a]­purin‐9‐one hydrate

In the title compound, C₁₃H₁₃N₅O₄·H₂O (4,5′‐cyclo­wyosine·H₂O), the cyclization forces a syn arrangement of the aglycon with respect to the sugar moiety. The ribo­furan­ose part of the mol­ecule displays a β‐d configuration with an envelope C1′‐endo pucker. The mol­ecules are arranged in columns along the short a axis and are linked to water mol­ecules through O—H?O and O—H?N hydrogen bonds.     

Transition metal complexes with thiosemicarbazide‐based ligands. XLIV. Aqua(3‐hydroxy‐5‐hydroxymethyl‐2‐methylpyridine‐4‐carboxaldehyde 3‐­methylisothiosemicarbazone‐κ3O,N1,N4)nitratocopper(II) nitrate

The title complex, [Cu(NO₃)(C₁₀H₁₄N₄O₂S)(H₂O)](NO₃), is the first metal complex with a Schiff base derived from iso­thio­semicarbazide and pyridoxal (pyridoxal is 3‐hydroxy‐5‐­hydroxy­methyl‐2‐methyl­pyridine‐4‐carbox­aldehyde). The Cu^II environment is a square pyramid, the equatorial plane of which is formed by the tridentate ONN‐coordinated iso­thio­semicarbazone and one water mol­ecule, while the nitrate ligand is in the apical position. The existence of numerous strong intermolecular hydrogen bonds, and weak C—H?O and C—H?π interactions, leads to a three‐dimensional supramolecular structure.     

(+)‐3,11‐Dioxoandrost‐4‐ene‐17β‐carboxyl­ic acid: catemeric hydrogen bonding in a steroidal keto acid

The title keto acid, C₂₀H₂₆O₄, forms carboxyl‐to‐ketone hydrogen‐bonding catemers [O?O = 2.653 (5) Å and O—H?O = 172 (5)°], linking translationally related mol­ecules via the A‐ring ketone. The two mol­ecules in the cell form two parallel counter‐directional chains, screw‐related in b. A total of four intermolecular C—H?O=C close contacts was found, involving both ketone functions.     

()‐12‐Oxotri­cyclo­[6.2.2.01,6]­dodec­ane‐10‐carboxyl­ic acid: hydrogen bonding in a tricyclic δ‐keto acid

The ring system of the title compound, C₁₃H₁₈O₃, was synthesized by addition of ethyl acryl­ate to the dien­amine of 2‐octalone. The keto acid aggregates in the solid as acid‐to‐acid dimers [O?O = 2.663 (2) Å and O—H?O = 170 (3)°] whose centrosymmetric hydrogen bonds lie across the a edges and the center of the chosen cell. Three intermolecular C—H?O close contacts within 2.7 Å were found involving the ketone group.     

Hexa­methyl­enetetra­mine–4‐nitro­catechol–water (1/2/1)

In the title adduct, 1,3,5,7‐tetra­aza­tri­cyclo[3.3.1.1^3,7]dec­ane–4‐nitro­benzene‐1,2‐diol–water (1/2/1), C₆H₁₂N₄·2C₆H₅NO₄·H₂O, the hexa­methyl­ene­tetra­mine mol­ecule acts as an acceptor of intermolecular O—H?N hydrogen‐bonding interactions from the water mol­ecule and the hydroxy groups of one of the two symmetry‐independent 4‐nitro­catechol mol­ecules. The structure is built from molecular layers which are stabilized by three intermolecular O—H?O, two intermolecular O—H?N and four intermolecular C—H?O hydrogen bonds. The layers are further interconnected by one additional intermolecular O—H?N and two intermolecular C—H?O hydrogen bonds.     

tert‐Butyl N‐{2‐[N‐(N,N′‐dicyclohexyl­ureido­carbonyl­ethyl)­carbamoyl]prop‐2‐yl}carbamate

The title compound, C₂₅H₄₄N₄O₅, exhibits a turn with the main chain reversing direction, held together by an intramol­ecular N—H?O hydrogen bond. In the urea fragment, a notable amide C—N bond between the carboxyl C and the tertiary N atom shows marked single‐bond character [1.437 (2) Å]. The dihedral angle of the β‐alanyl residue, centrally located in the turn, is gauche [69.2 (2)°]. The packing is mediated by two intermolecular hydrogen bonds and van der Waals contacts involving the methyl moieties and the cyclo­hexyl rings.     

Ferrocene compounds. XXXVIII. Di­methyl ferrocene‐1,1′‐di­carboxyl­ate

In the title compound, [Fe(C₇H₇O₂)₂], the cyclo­penta­dienyl rings and the two attached methoxy­carbonyl groups, in an anti arrangement, form an extended π‐conjugated system. The Fe—C distances range from 2.035 (3) to 2.061 (3) Å and the average value of the C—C bond lengths in the two cyclo­penta­dienyl rings is 1.419 (5) Å. The rings are almost parallel to one another [1.0 (2)°] and are mutually twisted from an eclipsed conformation by only 1.8 (3)° (average value). The methoxy­carbonyl groups are twisted out of the plane of the cyclo­penta­dienyl rings by 6.5 (4) and 15.7 (4)°, respectively. The mol­ecules are joined into dimers by intermolecular C—H⃛O hydrogen bonds that form ten‐membered rings. The same types of hydrogen bonds form eight‐membered rings and infinite chains along the b axis.     

3,7‐Dibromohinokitiol: a redetermination

The structure of the title compound (systematic name: 3,7‐di­bromo‐2‐hydroxy‐6‐iso­propyl­cyclo­hepta‐2,4,6‐trien‐1‐one), C₁₀H₁₀Br₂O₂, previously described by Ito, Fukazawa & Iitaka [Tetrahedron Lett. (1972), 13 , 745–749], has been redetermined. Strong inter‐ and intramolecular hydrogen bonds, with H...O distances of 2.17 (9) and 2.06 (6) Å, respectively, are observed. There are also two short Br...Br and two short Br...(ring centroid) interactions. Important dimensions include C—O(carbonyl) = 1.252 (5) Å, C—O(hydroxyl) = 1.355 (5) Å, C—Br(3‐position) = 1.904 (4) Å and C—Br(7‐­position) = 1.905 (4) Å, and an O—C—C—O ring torsion angle of −6.7 (6)°.