1-(1-Hydr­oxy-9H-carbazol-2-yl)-3-methyl­but-2-en-1-one (2024)

A number of carbazole alkaloids with intriguing novel structures and usefulbiological activities were isolated from natural sources over the pastdecades, which led towards the development of new synthetic strategies for thesynthesis of carbazole and its derivatives (Chakraborty, 1993). Amongthephysiologically active carbazoles found aree pyranocarbazole alkaloids, whichhave a C-13, C-18 or C-23 framework (Knölker & Reddy, 2002). The basic unit isthe C-12 carbazole nucleus with one carbon attached as a methyl, formyl,carboxylic or ester group. This C-13 unit then leads to C-18 or C-23 carbazolealkaloids depending on whether it combines with a hemi-terpenoid or amono-terpenoid unit. Another observation is that in all the pyranocarbazolederivatives isolated so far, the oxygen atom of the pyran ring is attached tocarbon-2 of the carbazole nucleus to form essentiallypyrano[3,2-a]carbazole as in grinimbine. Patel (1982,and references therein) has reported thesynthesis of indolo[3,2-h]chromanones from 1-hydroxycarbazoles whichwere then converted to isomers of grinimbine. Here the yields of compound werereported to be moderate since it was obtained along with the respective2-acryloyl-1-hydroxycarbazole.

In this context we aimed to prepare pyrano[2,3-a]carbazoles using1-hydroxycarbazoles as starting synthons under various reaction conditions(Kavitha & Rajendra Prasad, 2003a,b, andreferences therein).Using the catalyst mixtureAlCl₃/POCl₃ along with 9-carbazole-1-ol and 3,3-dimethyacrylic acid as thereactants we obatined a mixture of two products i.e.,1-(1-hydroxy-9H-carbazol-2-yl)-3-methylbutan-1-one and2,2-dimethyl-2,3-dihydropyrano-[2,3-a]carbazol-4(11H)-one as described in an earlier publication (Sridharan etal., 2008) and in Figure 1. The structure of the cyclized compound2,2-dimethyl-2,3-dihydropyrano-[2,3-a]carbazol-4(11H)-one was described in the earlier structure report (Sridharanet al., 2008). Here we would like to present the structure ofthesecond compound isolated,1-(1-hydroxy-9H-carbazol-2-yl)-3-methylbutan-1-one.

The title compound crystallizes in a triclinic setting with twocrystallographically independent molecules, A and B (Figure 2). The twomolecules are virtually superimposable (see overlay of the two structures inFigure 3) but a PLATON symmetry check did not reveal any translationalor other pseudosymmetry even when using relaxed tolerances (Spek,2009). Bothindependent molecules are planar, r.m.s. deviations from planarity are 0.053and 0.079 Ų, respectively, and they are tilted against each other withinthe structure with a dihedral angle of the planes of the A and B molecules of53.11(2)°.

Each molecule exhibits a strong intramolecular O—H···O hydrogen bond betweenthe phenolic hydroxyl group and the keto oxgen atom (Table 1). In additioneach type of molecules is connected via pairs of N—H···O hydrogenbonds to another molecule of the same type to form centrosymmetric A₂ andB₂ dimers (the planes of the dimers are parallel but slightly shiftedagainst each other, Figure 4). The dimers are in turn arranged in offsetπ-stacks that are extending along the a axis direction. The metrics ofthe interaction are best given for the interaction of the phenol rings C7A toC12A and C7B to C12B with their respective symmetry equivalent counterparts at2 - x, -y, 1 - z and 1 - x, -y, 2 -z. For these the centroid to centroid distances are 4.083(1) and4.089(1) Å, the interplanar distances are 3.2985(6) and 3.2992(7) Å, andthe slippages are 2.407 and 2.415 Å, respectively. The offset of the dimersand the tilt angle of the molecules allows for the formation of alternatingC—H···π interactions between A and B molecules of parallel stacks.C—H···π interactions are given in Table 1, with ring centroids 1, 2 and 3being the phenyl rings C1B to C6B, C7A to C12A and C1A to C6A, respectively.

For synthetic strategies for thesynthesis of carbazole and its derivatives, see: Chakraborty (1993).For the isolation of pyranocarbazoles from various plant species, see: Knölker& Reddy (2002, and references therein). For the synthesis of relatedcompounds, see: Kavitha & Rajendra Prasad(2003a,b); Patel (1982). For thestructure of the second product of the reaction yielding the title compound,see: Sridharan et al. (2008). PLATON (Spek, 2009) wasused forstructure validation and to test for pseudosymmetry.

The title compound was synthesized as described previously by Sridharan etal. (2008): 9-Carbazole-1-ol (0.001 mol) and 3,3-dimethylacrylicacid(0.001 mol) were dissolved in the mixture of an ice-cold solution ofAlCl₃/POCl₃ (400 mg/ 6 ml) and kept at room temperature for 24 h. Thereaction process as monitored by TLC indicated the formation of two compounds.After completion of the reaction (disappearance of starting material), theresidue was poured onto ice water. The solid separated out was filtered, driedand then separated by column chromatography on silica gel using petroleumether/ ethyl acetate (98:2) as eluents to yield the title compound1-(1-hydroxy-9H-carbazol-2-yl)-3-methylbutan-1-one and2,2-dimethyl-2,3-dihydropyrano[2,3-a]carbazol-4(11H)-one,respectively as yellow prisms (Figure 1). The title compound wasrecrystallized from ethanol. Yield: 0.114 g (43%), m.p. 482- 484 K (209 -211°C).

Hydrogen atoms were placed in calculated positions with C—H bond distances of0.95 Å (aromatic H), 0.88 Å (N—H) or 0.84 Å (O—H) and were refinedwith an isotropic displacement parameter 1.5 (methyl, hydroxyl) or 1.2 times(all others) that of the adjacent carbon or oxygen atom. Methyl and hydroxylhydrogen atoms were allowed to rotate at fixed angle around the C—C/O bondto best fit the experimental electron density.

A number of carbazole alkaloids with intriguing novel structures and usefulbiological activities were isolated from natural sources over the pastdecades, which led towards the development of new synthetic strategies for thesynthesis of carbazole and its derivatives (Chakraborty, 1993). Amongthephysiologically active carbazoles found aree pyranocarbazole alkaloids, whichhave a C-13, C-18 or C-23 framework (Knölker & Reddy, 2002). The basic unit isthe C-12 carbazole nucleus with one carbon attached as a methyl, formyl,carboxylic or ester group. This C-13 unit then leads to C-18 or C-23 carbazolealkaloids depending on whether it combines with a hemi-terpenoid or amono-terpenoid unit. Another observation is that in all the pyranocarbazolederivatives isolated so far, the oxygen atom of the pyran ring is attached tocarbon-2 of the carbazole nucleus to form essentiallypyrano[3,2-a]carbazole as in grinimbine. Patel (1982,and references therein) has reported thesynthesis of indolo[3,2-h]chromanones from 1-hydroxycarbazoles whichwere then converted to isomers of grinimbine. Here the yields of compound werereported to be moderate since it was obtained along with the respective2-acryloyl-1-hydroxycarbazole.

In this context we aimed to prepare pyrano[2,3-a]carbazoles using1-hydroxycarbazoles as starting synthons under various reaction conditions(Kavitha & Rajendra Prasad, 2003a,b, andreferences therein).Using the catalyst mixtureAlCl₃/POCl₃ along with 9-carbazole-1-ol and 3,3-dimethyacrylic acid as thereactants we obatined a mixture of two products i.e.,1-(1-hydroxy-9H-carbazol-2-yl)-3-methylbutan-1-one and2,2-dimethyl-2,3-dihydropyrano-[2,3-a]carbazol-4(11H)-one as described in an earlier publication (Sridharan etal., 2008) and in Figure 1. The structure of the cyclized compound2,2-dimethyl-2,3-dihydropyrano-[2,3-a]carbazol-4(11H)-one was described in the earlier structure report (Sridharanet al., 2008). Here we would like to present the structure ofthesecond compound isolated,1-(1-hydroxy-9H-carbazol-2-yl)-3-methylbutan-1-one.

The title compound crystallizes in a triclinic setting with twocrystallographically independent molecules, A and B (Figure 2). The twomolecules are virtually superimposable (see overlay of the two structures inFigure 3) but a PLATON symmetry check did not reveal any translationalor other pseudosymmetry even when using relaxed tolerances (Spek,2009). Bothindependent molecules are planar, r.m.s. deviations from planarity are 0.053and 0.079 Ų, respectively, and they are tilted against each other withinthe structure with a dihedral angle of the planes of the A and B molecules of53.11(2)°.

Each molecule exhibits a strong intramolecular O—H···O hydrogen bond betweenthe phenolic hydroxyl group and the keto oxgen atom (Table 1). In additioneach type of molecules is connected via pairs of N—H···O hydrogenbonds to another molecule of the same type to form centrosymmetric A₂ andB₂ dimers (the planes of the dimers are parallel but slightly shiftedagainst each other, Figure 4). The dimers are in turn arranged in offsetπ-stacks that are extending along the a axis direction. The metrics ofthe interaction are best given for the interaction of the phenol rings C7A toC12A and C7B to C12B with their respective symmetry equivalent counterparts at2 - x, -y, 1 - z and 1 - x, -y, 2 -z. For these the centroid to centroid distances are 4.083(1) and4.089(1) Å, the interplanar distances are 3.2985(6) and 3.2992(7) Å, andthe slippages are 2.407 and 2.415 Å, respectively. The offset of the dimersand the tilt angle of the molecules allows for the formation of alternatingC—H···π interactions between A and B molecules of parallel stacks.C—H···π interactions are given in Table 1, with ring centroids 1, 2 and 3being the phenyl rings C1B to C6B, C7A to C12A and C1A to C6A, respectively.

For synthetic strategies for thesynthesis of carbazole and its derivatives, see: Chakraborty (1993).For the isolation of pyranocarbazoles from various plant species, see: Knölker& Reddy (2002, and references therein). For the synthesis of relatedcompounds, see: Kavitha & Rajendra Prasad(2003a,b); Patel (1982). For thestructure of the second product of the reaction yielding the title compound,see: Sridharan et al. (2008). PLATON (Spek, 2009) wasused forstructure validation and to test for pseudosymmetry.

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and publCIF (McMahon & Westrip, 2008).