Barium Hydroxide

Ba(OH)2

[17194-00-2]  · BaH2O2  · Barium Hydroxide  · (MW 171.35) (.H2O)

[22326-55-2]  · BaH4O3  · Barium Hydroxide  · (MW 189.37) (.8H2O)

[12230-71-6]  · BaH18O10  · Barium Hydroxide  · (MW 315.48)

(used as a base catalyst in a variety of organic reactions such as decarboxylations, aldol or aldol-type reactions, Claisen-Schmidt reactions, Michael additions, and Wittig-Horner reactions)

Physical Data: Ba(OH)2.H2O, d 3.743 g cm-3. Ba(OH)2.8H2O, mp 78 °C; d 2.180 g cm-3.

Solubility: monohydrate is slightly sol water. Octahydrate is freely sol water and methanol, slightly sol ethanol; practically insol acetone.

Form Supplied in: monohydrate, white solid; octahydrate, transparent crystals or white masses.

Handling, Storage, and Precautions: poison; corrosive. May be fatal if swallowed, inhaled, or absorbed through skin. Material is extremely destructive to tissue of the mucous membranes and upper respiratory tract, eyes, and skin.1 Incompatible with acids. Absorbs moisture and CO2 from air. Use only in a chemical fume hood. Avoid contact with eyes, skin, and clothing. Wash thoroughly after handling. Keep container tightly closed.

Introduction.

The octahydrate, Ba(OH)2.8H2O, is the most common form. Upon dehydration at elevated temperatures (200-500 °C) it is converted to the anhydrous form. On standing at rt, anhydrous Ba(OH)2 is partially rehydrated and the resulting equilibrium water content is related to the dehydration temperature. The solids resulting from such a treatment are referred to in the literature as activated barium hydroxides. An activated Ba(OH)2 is a mixture of anhydrous Ba(OH)2 and the monohydrate in variable ratios. In the crystal structure, the monohydrate is the main component over the solid surface.1 The most popular activated Ba(OH)2 is sometimes referred to as C-200 (i.e. dehydrated at 200 °C) and was determined to be Ba(OH)2.0.8H2O.2

Partial Hydrolysis of Dimethyl Dicarboxylates.

The monomethyl ester of undecanedioic acid was prepared by partial hydrolysis of the dimethyl ester with methanolic Ba(OH)2 (eq 1). The precipitation of the barium salt of the monoester prevents further hydrolysis to the diacid. The procedure has an advantage over the fractional distillation of partially esterified diacids, particularly for the high-boiling half esters which may disproportionate at elevated temperatures. This method was not satisfactory for low molecular weight half esters because of the higher solubility of their barium salts in methanol.3

Ketocarboxylic Acids from Ketodicarboxylic Esters.

The ketodicarboxylate derivative (1) was hydrolyzed and decarboxylated when treated with Ba(OH)2.8H2O in refluxing ethanol for 20 h to give the crystalline g-keto acid (2) in 98% yield (eq 2).4

Monocarboxylic Acids from Dicarboxylic Acid Anhydrides.

In the total synthesis of (±)-pentalenolactone, the intermediate dicarboxylic anhydride (3) was converted to carboxyenone (4) upon treatment with 1.2 equiv of Ba(OH)2.8H2O in water and heating at reflux temperature for 5 h (eq 3). The cleavage of the anhydride, the formation of the enone from the b-methoxy silyl enol ether, and the decarboxylation of the vinylogous b-keto barium carboxylate were all achieved in one operation giving the desired product (4) in 99% yield.5

Reaction with a-Chlorolactams: a Stereoselective Favorskii-Type Ring Contraction.

Treatment of the bicyclic a-chlorovalerolactams (5), (6), and (7) with aqueous Ba(OH)2 at reflux temperature promoted a Favorskii-type ring contraction to give the octahydroindoles and octahydroisoindoles (8), (9), and (10) respectively. While chlorolactams (5) and (6) rearrange in a diastereoselective fashion (eqs 4 and 5), (7) gave a 1:1 mixture of (10a) and (10b) (eq 6). The observed diastereoselectivity was attributed to cis-1,3 and cis-1,2 steric interactions in (5) and (6), respectively, and the lack of such interactions in (7).6

Preparation of Diacetone Alcohol.

Heating acetone in a flask fitted with a Soxhlet extractor containing Ba(OH)2 for 95-120 h gave 71% yield of distilled diacetone alcohol (eq 7).7

Heterogeneous Claisen-Schmidt Condensation.

Activated Ba(OH)2 (C-200) was used as a heterogeneous catalyst in Claisen-Schmidt condensations. The method was applied to reactions of various aromatic aldehydes with methyl ketones to give the corresponding styryl ketones. Generally, the aldehyde is mixed with the methyl ketone (2 equiv) and the C-200 catalyst (12%) in ethanol and the mixture is heated at reflux for 1 h. The yields ranged from 25 to 100% (eq 8).8 The procedure was extended to the synthesis of o-hydroxychalcones, e.g. the reaction of o-hydroxyacetophenone with benzaldehyde in 96% ethanol and a catalytic amount of C-200 gave o-hydroxychalcone in 89% yield (eq 9).9

The yields from these reactions were as good as or better than other methods. Secondary reactions such as the Cannizzaro reaction of aldehydes and aldol additions of ketones were not observed. Unlike other methods, protection of the phenol was not necessary and the product did not cyclize to the flavenone. The absence of cyclized products as well as the (E) configuration of the alkenic bond were explained by a rigid transition state in which the carbanion and aldehyde are adsorbed on the insoluble catalyst surface.9

Michael Addition to Chalcones.

Partially dehydrated Ba(OH)2 efficiently catalyzed the Michael additions of active methylene compounds to chalcones. The reaction temperature and amount of catalyst determined the isolated product (eq 10). Thus the reaction of chalcone with ethyl acetoacetate (25 mmol each) at rt in EtOH with 5 mg catalyst gave primarily the Michael addition product (11) in 90% yield. By increasing the amount of catalyst to 50 mg at rt, the reaction proceeded further to give the cyclic product (12) in 95% yield, resulting from Michael addition followed by intramolecular aldol reaction. The dehydrated cyclic adduct (13) was the major product (80%) at reflux temperature.10

Addition of Diethyl Malonate to Coumarin.

An attempted Michael addition of diethyl malonate to coumarin (14) in the presence of solid Ba(OH)2 (C-200) in EtOH gave the unusual 1,2-addition-elimination product (15) in 30% yield (eq 11). The result was explained in terms of the structure of the catalyst and the chelation of coumarin to the barium ion of the lattice.11

Synthesis of D2-Isoxazolines and D2-Pyrazolines.

The addition of NH2OH and PhNHNH2 to chalcone and related enones (16) was catalyzed by Ba(OH)2 (C-200) to give good yields of D2-isoxazoline (17) and D2-pyrazoline (18) derivatives respectively (eq 12). The products were obtained in yields between 65 and 75% and with complete regioselectivity.12

Oxidation of Benzyl Halides to Benzaldehydes.

Benzyl halides were oxidized to benzaldehydes by Dimethyl Sulfoxide in the presence of activated Ba(OH)2 (C-200) in 1,4-dioxane. The optimum conditions include the use of a 5 M solution of the aryl halide in 1,4-dioxane with 3 equiv of DMSO and about 0.2 equiv of the Ba(OH)2 catalyst, then heating the mixture at 130 °C for 3 h. The reaction does not take place in the absence of the C-200 catalyst. The effect of each variable in the reaction on the yield was studied, but no specific yields were given for isolated products except for PhCH2Cl, which was reported as 100%. The proposed mechanism of the reaction involves an initial displacement of the halide by DMSO followed by elimination of Me2S with the aid of the basic OH groups on the catalyst surface (eq 13).13

Hydrolysis of 2-Alkoxyimidazolines.

In a procedure for the stereoselective synthesis of vicinal diamines, several alkenes were converted into 2-alkoxyimidazolines (19) via consecutive reactions with cyanamide/NBS, HCl/EtOH, and Et3N/EtOH. The intermediates (19) were hydrolyzed with Ba(OH)2 at 120 °C for 18 h (eq 14) to give the diamines (20) in 79-99% yields for this step and in 61-71% overall yields.14

A Skeletal Rearrangement in a 6b,19-Oxido Steroid.

When 6b,19-oxido-2,17-dihydroxyandrosta-1,4-dien-3-one (21) was heated at reflux with Ba(OH)2.8H2O in pyridine for 22 h, and then worked up under acidic conditions, it rearranged to the furopyranone (23) in 80-85% yield (eq 15). The rearrangement included a ring B contraction, a double bond isomerization and a benzylic acid rearrangement. The acidic work-up caused the carboxy intermediate (22) to cyclize with the vinyl ether to give (23).15

Wittig-Horner Reaction.

Activated Ba(OH)2 (C-200) catalyzed the reactions of aldehydes with triethylphosphonoacetates (24) in 1,4-dioxane in the presence of a small amount of water at 70 °C to give the corresponding 3-substituted ethyl acrylates (25) (eq 16). The yields of the products from aromatic aldehydes ranged from 0% for indole-3-carbaldehyde to 100% for furfural and m-nitrobenzaldehyde. The method was applied to hindered aldehydes such as pyrene-1-carbaldehyde and to unsaturated aldehydes such as cis- or trans-citral.16 The reaction was also applied to various aliphatic aldehydes using 2-oxoalkanephosphonates to give the corresponding (E)-a,b-unsaturated ketones in high yields and stereoselectivities.17

Deacylation of 2-Alkyl-2-halo-1,3-dicarbonyl Compounds.

Treatment of various a-alkyl-a-bromoacetoacetic esters (26) with a suspension of anhydrous Ba(OH)2 in absolute ethanol at 0 °C for 30 min effected their deacetylation and gave the corresponding a-bromo esters (27) in very good yields without any competing saponification or Favorskii rearrangement (eq 17).18 The starting a-alkyl-a-bromoacetoacetic esters were prepared from the corresponding acetoacetic esters in two steps (NaH/RX then NaH/Br2) and used directly in the above reaction. The overall yields for the three-step sequence ranged between 70 and 85%. A similar deacylation of the substituted 4-alkyl-4-chloroheptane-3,5-dione (28) was reported in the synthesis of racemic juvenile hormone using Ba(OH)2 in ethanol at 0 °C for 25 min (eq 18) to give the corresponding a-chloro ketone (29).19

Removal of the N-Protecting Benzyloxycarbonyl Group.

The alkynyl amine (31) was obtained in 75% yield by removal of the N-protecting benzyloxycarbonyl group from the benzyl carbamate (30) using 0.15 M Ba(OH)2 in 3:2 glyme-H2O at reflux temperature for 40 h (eq 19). Other reagents (Me3SiI, BBr3, Me2BBr, BF3/EtSH, AlCl3/EtSH, MeLi/LiBr, or KOH/EtOH) caused partial destruction of the alkyne.20


1. For complete safety data on Ba(OH)2.8H2O, see The Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, 1988; Vol. 1, p 335C.
2. Barrios, J.; Marinas, J. M.; Sinisterra, J. V. BSB 1986, 95, 107.
3. Durham, L. J.; McLeod, D. J.; Cason, J. OSC 1963, 4, 635.
4. Miller, R. B.; Nash, R. D. T 1974, 30, 2961.
5. Danishefsky, S.; Hirama, M.; Gombatz, K.; Harayama, T.; Berman, E.; Schuda, P. F. JACS 1979, 101, 7020.
6. Henning, R.; Urbach, H. TL 1983, 24, 5339.
7. Conant, J. B.; Tuttle, N. OSC 1944, 1, 199.
8. Sinisterra, J. V.; Garcia-Raso, A.; Cabello, J. A.; Marinas, J. M. S 1984, 502.
9. Alcantara, A. R.; Marinas, J. M.; Sinisterra, J. V. TL 1987, 28, 1515.
10. (a) Garcia-Raso, A.; Garcia-Raso, J.; Campaner, B.; Mestres, R.; Sinisterra, J. V. S 1982, 1037. For a discussion on the mechanism of the Michael addition of active methylene compounds to chalcone, see (b) Iglesias, M.; Marinas, J. M.; Sinisterra, J. V. T 1987, 43, 2335.
11. Sinisterra, J. V.; Marinas, J. M. M 1986, 117, 111.
12. Sinisterra, J. V. React. Kinet. Catal. Lett. 1986, 30, 93.
13. Climent, M. S.; Marinas, J. M.; Sinisterra, J. V. React. Kinet. Catal. Lett. 1987, 34, 201.
14. Kohn, H.; Jung, S.-H. JACS 1983, 105, 4106.
15. Chorvat, R. J.; Bible, Jr., R. H.; Swenton, L. T 1975, 31, 1353.
16. Sinisterra, J. V.; Mouloungui, Z.; Delmas, M.; Gaset, A. S 1985, 1097.
17. Alvarez-Ibarra, C.; Arias, S.; Banon, G.; Fernandez, M. J.; Rodriguez, M.; Sinisterra, V. CC 1987, 1509.
18. Stotter, P. L.; Hill, K. A. TL 1972, 4067.
19. Johnson, W. S.; Li, T.-t.; Faulkner, D. J.; Campbell, S. F. JACS 1968, 90, 6225.
20. Overman, L. E.; Sharp, M. J. TL 1988, 29, 901.

Ahmed F. Abdel-Magid

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA



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