Hydrobromic Acid1

BrH

[10035-10-6]  · BrH  · Hydrobromic Acid  · (MW 80.91)

(preparation of alkyl and vinyl bromides; preparation of phenols from alkyl aryl ethers; in combination with hydrogen peroxide is an in situ source of bromine for the preparation of alkyl and aryl bromides)

Physical Data: aqueous solution forms a constant boiling azeotrope containing ca. 48% HBr at 760 mmHg; d = 1.49 g cm-3. Anhydrous gas, d 2.71 g L-1; mp -86.9 °C; bp -66.8 °C.

Solubility: very sol water and protic solvents.

Form Supplied in: as anhydrous gas in cylinders; as aqueous solutions of various concentrations; widely available in all forms.

Analysis of Reagent Purity: titration.

Handling, Storage, and Precautions: hydrogen bromide is a corrosive, colorless, nonflammable gas which forms a white cloud when exposed to air; as concentrated solutions, hydrobromic acid is a colorless to light yellow corrosive liquid which fumes when exposed to air; the acid can cause severe skin burns, damage to the respiratory and digestive tract, and/or visual damage; repeated exposure may cause dermatitis and photosensitization; the gas and solutions of hydrobromic acid should be handled with adequate ventilation and proper skin and eye protection. Use in a fume hood.

Acid Catalysis.

Hydrogen Bromide is completely ionized in all but the most concentrated aqueous solutions, making it a strong Lewis acid. However, the expense of hydrobromic acid relative to Hydrochloric Acid and other mineral acids, as well as the greater nucleophilicity of bromide, has limited its use as an acid catalyst.

Bromomethylation.

Concentrated hydrobromic acid or anhydrous hydrogen bromide have been used with Paraformaldehyde or 1,3,5-trioxane for the bromomethylation of aromatic compounds (eq 1). Formation of bis(bromomethyl) ether, a carcinogenic compound, under the reaction conditions is problematic. This side reaction has limited the use of the bromomethylation process. Phenols are so reactive under the reaction conditions that they are frequently deactivated through preparation of their acyl derivatives prior to bromomethylation. The reaction may be run in the presence of Brønsted acid catalysts.2 Treatment of dibenzyl diselenide with Zinc and hydrobromic acid followed by paraformaldehyde and hydrogen bromide produced high yields of bromomethyl benzyl selenide (eq 2).3 Analogous chemistry is observed with benzyl sulfide (eq 3). Treatment of an aryl alkyl ketone with Bis(dimethylamino)methane and hydrogen bromide has produced moderate yields of the ketone, which was bromomethylated a to the carbonyl (eq 4).4

Addition to Single Bonds in Three-Membered Rings.

Hydrogen bromide is less commonly used for the preparation of derivatives of terpenes containing three-membered rings than hydrochloric acid. Cleavage of cyclopropanes produces addition products which are expected to arise from bromide addition to the most stable carbonium ion (analogous to Markovnikov addition), some rearrangements do occur, and steric factors do play a role in the reaction (eq 5). Simple alkyl derivatives of the parent cyclopropane can give polymeric materials as the main product. As an example, treatment of cis-carane with hydrogen bromide results in cleavage of the cyclopropane ring with isolation of the tertiary bromide.5

Cyclopropylcarbinols react with concentrated hydrobromic acid under mild conditions to yield 1-bromo-3-butenes (eq 6).6 The reaction is regiospecific with secondary and some tertiary alcohols. With alkynic cyclopropylcarbinols, stereospecificity of the product double bond can be controlled through the use of Octacarbonyldicobalt.7

In acetic acid, acyl cyclopropane derivatives add anhydrous hydrogen bromide to yield 4-bromobutanone derivatives (eq 7). This addition is stereo- as well as regioselective.8

Oxiranes react readily with hydrobromic acid to yield addition products (eq 8). The reaction proceeds with inversion at carbon. The expected product is that in which the bromide adds to the least-hindered carbon. Addition to epoxycyclohexanes gives products in which attack of bromide is axial.9 Analogous chemistry is observed with aziridines (eq 9).10

Addition to Single Bonds in Four-, Five-, and Six-Membered Rings.

Although the parent acylcyclobutanes are stable to hydrogen bromide, [3.2.2]propellanes, [4.2.2]propellanes, and cubanes react to give addition products (eqs 10 and 11) or rearrangement products (eq 12), as shown.11

Oxetanes (eq 13) and tetrahydrofurans (eq 14) can be opened by anhydrous hydrogen bromide under a variety of conditions.12

Four-, five-, and six-membered lactones add anhydrous hydrogen bromide to yield the acyclic bromide (eq 15). When run in glacial acetic acid, the free carboxylic acid is isolated; in alcohols, the ester is produced.13

Reaction with Ethers.

Ethers react with hydrogen bromide under a variety of conditions to yield the corresponding bromide and alcohol (eq 16). Acetic acid is often used as solvent, but other carboxylic acids have also been used. Frequently, under the reaction conditions, the alcohol is also converted to its bromide.14 Reports of explosive reactions of ethers and hydrogen bromide have been reviewed.15

Aryl methyl ethers can be cleaved to phenols with hydrogen bromide in glacial acetic acid or by concentrated hydrobromic acid.16 This transformation is commonly accomplished using boron trihalides, Pyridinium Chloride, or Iodotrimethylsilane.17

Addition to Carbon-Carbon Multiple Bonds.

Hydrogen bromide reacts with alkenes more rapidly than hydrogen chloride. When care is taken to avoid radical conditions, the products which are obtained are those expected from Markovnikov addition (eq 17). Iron(III) Chloride, iron(III) bromide, or Aluminum Bromide are the most commonly used Lewis acids to activate unreactive double bonds. Hydrobromination of double bonds under radical conditions can lead to mixtures of products. When an electron-withdrawing group is attached directly to the double bond, the bromide typically adds b to that group.18

Treatment of allene with anhydrous hydrogen bromide results in formation of the expected Markovnikov addition product and 1,3-dimethyl-1,3-dibromocyclobutane (eq 18). 1,3-Disubstituted allenes, when treated with anhydrous hydrogen bromide, produce mixtures of HBr addition products resulting from addition of the proton to either the central ketene carbon or to a terminal ketene carbon (eq 19). 1,1-Disubstituted allenes add the proton to the central allene carbon and bromide to the terminal carbon to produce 1,1-dialkyl-3-bromo-1-propenes (eq 20).19

Addition of hydrogen bromide to alkynes is typically slow. Addition of ammonium bromide salts or Copper(I) Bromide produces a dramatic acceleration in the rate of the addition (eqs 21 and 22). In the absence of radicals, the isolated products are typically those expected from Markovnikov addition,20 although mixtures of products have been reported when the carbon a to the triple bond bears an amine.21 Under radical conditions, hydrogen bromide adds to alkynes to yield anti-Markovnikov products.22 In the presence of Copper(II) Bromide and ammonium bromide, aqueous hydrobromic acid adds to vinylacetylene to yield 2-bromobutadiene (eq 23).23

Hydrobromic acid is superior to hydrochloric acid for the conversion of 3-acylprop-2-ynal diethyl acetals to 3-acylprop-2-enoic acids (eq 24).24

Reactions with Alcohols.

Hydrobromic acid reacts with primary, secondary, tertiary, allylic, benzylic, and propargylic alcohols to give the corresponding bromides (eq 25). As is the case with the conversion of alcohols to chlorides, a large number of alternative reagents are available. Although hydrobromic acid is readily available, greater selectivity is often achieved using reagents such as Zinc Bromide/Triphenylphosphine/Diethyl Azodicarboxylate, Phosphorus(III) Bromide, or PPh3/Carbon Tetrabromide. Treatment of alkyl phosphites, phosphonates, and diphenyl phosphinites with hydrogen bromide produces the alkyl bromide in which inversion at carbon has occurred. Yields are higher and conditions milder than the corresponding reaction with hydrogen chloride.25

The reactions of carbohydrates and their derivatives with hydrogen bromide at the anomeric hydroxy are especially facile examples of the conversion of alcohols to bromides.26

When treated with hydrogen bromide, cyclobutylcarbinol rearranges to cyclopentyl bromide (eq 26).27 The analogous [2.1.1]bicyclocarbinol produces the primary bromide with hydrogen bromide (eq 27).28

Concentrated hydrobromic acid reacts with 1,1-dialkylpropargyl alcohols to give products which are dependent upon the reaction conditions. Products isolated when 3-methylbut-1-yn-3-ol was the starting alcohol include 1-bromo-3,3-dimethylallene, 3-bromo-3-methyl-1-butyne, 1-bromo-3-methyl-1,3-butadiene, 1,3-dibromo-3-methylbutene, and 1,2,3-tribromo-3-methylbutane (eq 28). Tertiary propargyl alcohols, in the presence of copper(I) bromide, ammonium bromide, and 45-48% hydrobromic acid, rapidly produce 1-bromoallenes. Secondary propargyl alcohols produce 1-bromoallenes using 60% hydrobromic acid, copper(I) bromide, and ammonium bromide.29

Reactions with Diazo Compounds.

Arylamines can be converted to aryl bromides by treatment with Sodium Nitrite/hydrobromic acid/Copper or copper(I) bromide (eq 29).30 Hydrobromic acid converts a-diazo ketones to a-bromo ketones in good yield (eq 30).31 Pure enantiomers of serine and threonine give good yields and high enantiomeric purity of a-bromo acids when treated with nitrite and hydrobromic acid.32

Reactions with Nitriles.

Addition of anhydrous hydrogen bromide to nitriles produces imidoyl bromides (eq 31).33 Treatment of N-alkylimidoyl bromides with hydrogen bromide results in isolation of the corresponding iminium bromides (eq 32).34 Methylene bis(thiocyanate) reacts with hydrogen bromide to produce the cyclic imidoyl bromide (eq 33).35 Methyl and phenyl thiocyanate react with 2 equiv of hydrogen bromide to produce 1-bromothioformimidate salts (eq 34).36 Cyanogen di-N-oxide reacts with hydrobromic acid to produce the hydroxamoyl bromide analog of oxalyl bromide (eq 35).37

Reactions with Sulfur Compounds.

Thiols react with paraformaldehyde and hydrobromic acid to yield bromomethyl thioethers (see bromomethylation above). Benzenesulfonamides, benzenesulfonohydrazides, and benzenesulfinic acids can all react with hydrobromic acid to yield disulfides or sulfenyl bromides, depending upon the reaction conditions (eqs 36-38). Hydrogen bromide appears to be better than hydrogen chloride for the preparation of disulfides from benzenesulfonamides, but less satisfactory than hydrogen chloride for the conversion of benzenesulfonohydrazides to disulfides.38 Sulfoxides are converted into bromosulfonium bromides or sulfides (eq 39).39 Chloro(trifluoromethyl)sulfine reacts with anhydrous hydrogen bromide to produce 1-bromo-1-chloro-2,2,2-trifluoroethylsulfenyl bromide in high yield (eq 40).40 Additional information is included under the section on the in situ generation of Bromine (see below).

Reactions with Silicon Compounds.

Phenylsilanes react with hydrogen bromide to yield benzene and the bromosilane (eq 41). The reaction is more facile than the reaction with hydrogen chloride. Increasing the electronegativity of substituents on silicon decreases the ease with which the aryl-silicon bond is broken.41 t-Butyldimethylsilyl ethers of phenols are cleaved to phenols at rt using a mixture of hydrobromic acid and Potassium Fluoride (eq 42).42 Triethylaminosilanes are converted to the corresponding bromosilanes in the presence of hydrobromic acid/Sulfuric Acid (eq 43).43

Transhalogenation Reactions.

Alkyl chlorides can be converted to alkyl bromides using hydrogen bromide in the presence of iron(III) bromide (eq 44).44 This conversion can also be effected under neutral conditions by heating the chloride with a metal bromide in acetone, an alcohol, or ethyl bromide.45

Acid chlorides react with anhydrous hydrogen bromide to yield the corresponding acid bromides (eq 45).46 This conversion may also be effected using Bromotrimethylsilane.47

Trichloromethylsulfenyl chloride reacts with concentrated hydrobromic acid to yield trichloromethylsulfenyl bromide (eq 46).48 Dichloromethyl methyl sulfide produces dibromomethyl methyl sulfide when treated with anhydrous hydrogen bromide (eq 47).49

Bromide Isomerization.

a,a-Dibromo ketones equilibrate to a,a-dibromo ketones in the presence of dilute hydrobromic acid (eq 48).50

Organoselenium, Organogermanium, and Organorhenium Chemistry.

Selenols react with paraformaldehyde and hydrogen bromide to produce bromomethyl selenides (see bromomethylation above). Methyl phenyl selenides are cleaved by hydrogen bromide in acetic acid to yield phenyl selenols (eq 49).51 Alkyl phenyl selenoxides react with hydrogen bromide to yield the alkyl bromides (eq 50).52 Selenonium nitroylides give bromonitromethane derivatives when reacted with hydrogen bromide in ether (eq 51).53

1,1-Dihydroxy-2,3-diphenylgermirene is converted to the dibromide with anhydrous hydrogen bromide in benzene (eq 52).54

The pure enantiomer of the pseudotetrahedral rhenium alkyl complex in eq 53 reacts with concentrated hydrobromic acid to produce the pure reduced enantiomer. Cleavage of the rhenium-carbon bond occurs with retention at both carbon and rhenium.55

In Situ Generation of Bromine.

Dimethyl Sulfoxide reacts with hydrobromic acid at about 80 °C to produce dimethyl sulfide, water, and bromine (eq 54). The DMSO/HBr reagent has been used to oxidize 1,3-diketones to 1,2,3-triketones, acetophenones to phenylglyoxals, benzylamines to imines, and 4,5-dihydropyridazin-3(2H)-ones to pyridazin-3(2H)-ones.56 The combination is also effective in converting stilbenes, 1,2-dibromo-1,2-diarylethanes, and 2-bromo-1,2-diarylethanols to benzils.57 It is possible to use a catalytic amount of hydrogen bromide in some of these reactions.

Hydrobromic acid and Hydrogen Peroxide are an effective combination for the in situ generation of bromine (eq 55). This combination of reagents can be used for the bromination of alkenes and aromatics, for the preparation of bromohydrins from alkenes, and for the preparation of benzylic bromides.58

Hydrobromic acid is a source of bromine when irradiated in the presence of air or oxygen (eq 56). Ethylbenzene, when photooxidized, yields a mixture of acetophenone, 1-phenylethanol, and 1-phenylbromoethane.59

Related Reagents.

Formaldehyde-Hydrogen Bromide; Hydrogen Bromide.


1. (a) Brasted, R. C. In Comprehensive Inorganic Chemistry; Sneed, M. C.; Maynard, J. L.; Brasted, R. C., Eds.; Van Nostrand: New York, 1954; Vol. III, p 118. (b) Downs, A. J.; Adams, C. J. In Comprehensive Inorganic Chemistry; Bailar, J. C., Jr., Ed.; Pergamon: Oxford, 1973; Vol. 2, p 1280.
2. (a) Fields, D. L.; Miller, J. B.; Reynolds, D. D. JOC 1964, 29, 2640. (b) Schetty, G. HCA 1948, 31, 1229 (CA 1949, 43, 203d). (c) Bailey, P. S.; Bath, S. S.; Thomsen, W. F.; Nelson, H. H.; Kawas, E. E. JOC 1956, 21, 297. (d) Böhmer, V.; Marschollek, F.; Zetta, L. JOC 1987, 52, 3200. (e) Mitchell, R. H.; Iyer, V. S. SL 1989, 55.
3. Reich, H. J.; Jasperse, C. P.; Renga, J. M. JOC 1986, 51, 2981.
4. Moussavi, Z.; Depreux, P.; Lesieur, D. SC 1991, 21, 271.
5. Bardyshev, I. I.; Buinova, É. F.; Protashchik, I. V. JOU 1971, 7, 2398 (CA 1972, 76, 46 311z).
6. (a) Julia, M.; Julia, S.; Guegan, R. BSF 1960, 1072 (CA 1961, 55, 5567b). (b) Julia, M.; Julia, S.; Tchen, S.-Y. BSF 1961, 1849 (CA 1962, 57, 4535f). (c) Julia, M.; Julia, S.; Amaudric du Chaffaut, J. BSF 1960, 1735 (CA 1961, 55, 17 525d). (d) Gualtieri, F.; Teodori, E.; Bellucci, C.; Pesce, E.; Piacenza, G. JMC 1985, 28, 1621. (e) Julia, M.; Julia, S.; Stalla-Bourdillon, B.; Descoins, C. BSF 1964, 2533 (CA 1965, 62, 5182d). (f) Julia, M.; Descoins, C. BSF 1962, 1933 (CA 1963, 58, 12 414h). (g) Hatakeyama, S.; Numata, H.; Osanai, K.; Takano, S. CC 1989, 1893.
7. (a) McCormick, J. P.; Barton, D. L. CC 1975, 303. (b) Descoins, C.; Samain, D. TL 1976, 745.
8. (a) Takano, S.; Iwata, H.; Ogasawara, K. H 1978, 9, 1249. (b) Murray, R. K., Jr.; Morgan, T. K., Jr. JOC 1975, 40, 2642. (c) Grieco, P. A.; Masaki, Y. JOC 1975, 40, 150.
9. (a) For a discussion of factors influencing oxirane cleavage, see Buchanan, J. G.; Sable, H. Z. In Selective Organic Transformations; Thyagarajan, B. S., Ed.; Wiley: New York, 1972; Vol. 2, p 1. (b) For a review on the mechanism of epoxide cleavage, see Parker, R. E.; Isaacs, N. S. CRV 1959, 59, 737. (c) Bordwell, F. G.; Frame, R. R.; Strong, J. G. JOC 1968, 33, 3385. (d) Layachi, K.; Ariès-Gautron, I.; Guerro, M.; Robert, A. T 1992, 48, 1585. (e) Hudrlik, P. F.; Hudrlik, A. M.; Rona, R. J.; Misra, R. N.; Withers, G. P. JACS 1977, 99, 1993.
10. (a) Jenkins, T. C.; Naylor, M. A.; O'Neill, P.; Threadgill, M. D.; Cole, S.; Stratford, I. J.; Adams, G. E.; Fielden, E. M.; Suto, M. J.; Stier, M. A. JMC 1990, 33, 2603. (b) Heine, H. W.; Proctor, Z. JOC 1958, 23, 1554. (c) Buss, D. H.; Hough, L.; Richardson, A. C. JCS 1965, 2736. (d) Gensler, W. J. JACS 1948, 70, 1843.
11. (a) Eaton, P. E.; Jobe, P. G.; Reingold, I. D. JACS 1984, 106, 6437. (b) Eaton, P. E.; Jobe, P. G.; Nyi, K. JACS 1980, 102, 6636. (c) Eaton, P. E.; Millikan, R.; Engel, P. JOC 1990, 55, 2823.
12. (a) Wilson, E. R.; Frankel, M. B. JOC 1985, 50, 3211. (b) Paul, R.; Tchelitcheff, S. BSF 1953, 1014. (c) Ogawa, S.; Suzuki, M.; Tonegawa, T. BCJ 1988, 61, 1824.
13. (a) Zaugg, H. E. JACS 1950, 72, 2998. (b) Plieninger, H. CB 1950, 83, 268. (c) Stork, G.; Hill, R. K. JACS 1957, 79, 495. (d) Cottrell, I. F.; Hands, D.; Kennedy, D. J.; Paul, K. J.; Wright, S. H. B.; Hoogsteen, K. JCS(P1) 1991, 1091. (e) Orlek, B. S.; Wadsworth, H.; Wyman, P.; Hadley, M. S. TL 1991, 32, 1241.
14. (a) Landini, D.; Montanari, F.; Rolla, F. S 1978, 771. (b) Newkome, G. R.; Gupta, V. K.; Griffin, R. W.; Arai, S. JOC 1987, 52, 5480. (c) Grubbs, R. H.; Pancoast, T. A.; Grey, R. A. TL 1974, 2425.
15. Leleu, M. J. Cah. Notes Doc. 1976, 82, 127 (CA 1978, 88, 26 952d).
16. (a) Doxsee, K. M.; Feigel, M.; Stewart, K. D.; Canary, J. W.; Knobler, C. B.; Cram, D. J. JACS 1987, 109, 3098. (b) Ramesh, D.; Kar, G. K.; Chatterjee, B. G.; Ray, J. K. JOC 1988, 53, 212.
17. For a compilation of specific reagents used to convert aryl ethers to phenols, see Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989; p 502.
18. (a) Roedig, A. MOC 1960, V/4, 102. (b) Larock, R. C.; Leong, W. W. COS 1991, 4, 279. (c) Traynham, J. G.; Pascual, O. S. JOC 1956, 21, 1362. (d) Dowd, P.; Shapiro, M.; Kang, J. T 1984, 40, 3069.
19. (a) Taylor, D. R. CRV 1967, 67, 338. (b) Caserio, M. C. In Selective Organic Transformations; Thyagarajan, B. S., Ed.; Wiley: New York, 1970; Vol. 1, p 239.
20. (a) Hiyama, T.; Wakasa, N.; Ueda, T.; Kusumoto, T. BCJ 1990, 63, 640. (b) Baird, M. S.; Dale, C. M.; Lytollis, W.; Simpson, M. J. TL 1992, 33, 1521. (c) Grob, C. A.; Cseh, G. HCA 1964, 47, 194 (CA 1964, 60, 10 492g). (d) Cousseau, J. S 1980, 805.
21. Mori, M.; Higuchi, Y.; Kagechika, K.; Shibasaki, M. H 1989, 29, 853.
22. Skell, P. S.; Allen, R. G. JACS 1958, 80, 5997.
23. Keegstra, M. A.; Verkruijsse, H. D.; Andringa, H.; Brandsma, L. SC 1991, 21, 721.
24. Obrecht, D.; Weiss, B. HCA 1989, 72, 117.
25. (a) Hudson, H. R. S 1969, 112. (b) For a compilation of specific reagents used to convert alcohols to bromides, see Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989; pp 354 and 361.
26. (a) Fernez, A.; Stoffyn, P. J. T 1959, 6, 139 (CA 1959, 53, 21 675h). (b) Wysocki, R. J.; Siddiqui, M. A.; Barchi, J. J.; Driscoll, J. S.; Marquez, V. E. S 1991, 1005.
27. Demjanow, N. J. CB 1907, 40, 4959.
28. Wiberg, K. B.; Lowry, B. R.; Colby, T. H. JACS 1961, 83, 3998.
29. (a) Landor, S. R.; Patel, A. N.; Whiter, P. F.; Greaves, P. M. JCS(C), 1966, 1223. (b) Moulin, F. HCA 1951, 34, 2416 (CA 1952, 46, 7036h). (c) Favorskaya, T. A. ZOB 1940, 10, 461 (CA 1940, 34, 78451).
30. (a) Rinehart, K. L., Jr.; Kobayashi, J.; Harbour, G. C.; Gilmore, J.; Mascal, M.; Holt, T. G.; Shield, L. S.; Lafargue, F. JACS 1987, 109, 3378. (b) Bigelow, L. A. OSC 1941, 1, 135. (c) Hartwell, J. L. OSC 1955, 3, 185.
31. (a) Dauben, W. G.; Hiskey, C. F.; Muhs, M. A. JACS 1952, 74, 2082. (b) Pettit, G. R.; Green, B.; Das Gupta, A. K.; Whitehouse, P. A.; Yardley, J. P. JOC 1970, 35, 1381.
32. (a) Larchevêque, M.; Petit, Y. TL 1987, 28, 1993. (b) Larchevêque, M.; Mambu, L.; Petit, Y. SC 1991, 21, 2295.
33. Ulrich, H. The Chemistry of Imidoyl Halides; Plenum: New York, 1968; pp 66-68.
34. Ulrich, H. The Chemistry of Imidoyl Halides; Plenum: New York, 1968; p 100.
35. Johnson, F.; Madroñero, R. Adv. Heterocycl. Chem. 1966, 6, 131.
36. Allenstein, E.; Quis, P. CB 1964, 97, 3162 (CA 1965, 62, 1562g).
37. Grundmann, C.; Mini, V.; Dean, J. M.; Frommeld, H. D. LA 1965, 687, 191.
38. (a) Burawoy, A.; Vellins, C. E. JCS 1954, 90. (b) Burawoy, A.; Turner, C. JCS 1950, 469. (c) Yung, D. K.; Forrest, T. P.; Manzer, A. R.; Gilroy, M. L. JPS 1977, 66, 1009. (d) Searles, S.; Nukina, S. CRV 1959, 59, 1095.
39. Iselin, B. HCA 1961, 44, 61 (CA 1961, 55, 17 522d).
40. Fritz, H.; Sundermeyer, W. CB 1989, 122, 1757 (CA 1989, 111, 153 179a).
41. (a) Mitter, F. K.; Pollhammer, G. I.; Hengge, E. JOM 1986, 314, 1. (b) Hager, R.; Steigelmann, O.; Müller, G.; Schmidbaur, H. CB 1989, 122, 2115. (c) Schmidbaur, H.; Zech, J.; Rankin, D. W. H.; Robertson, H. E. CB 1991, 124, 1953. (d) Matsumoto, H.; Yokoyama, N.; Sakamoto, A.; Aramaki, Y.; Endo, R.; Nagai, Y. CL 1986, 1643. (e) Fritz, G.; Kummer, D. Z. Anorg. Allg. Chem. 1961, 308, 105 (CA 1961, 55, 18 412a).
42. Sinhababu, A. K.; Kawase, M.; Borchardt, R. T. S 1988, 710.
43. Bailey, D. L.; Sommer, L. H.; Whitmore, F. C. JACS 1948, 70, 435.
44. (a) Yoon, K. B.; Kochi, J. K. CC 1987, 1013. (b) Roedig, A. MOC 1960, V/4, 354.
45. (a) Bowers, S. D., Jr.; Sturtevant, J. M. JACS 1955, 77, 4903. (b) Bailey, W. J.; Fujiwara, E. JACS 1955, 77, 165. (c) Willy, W. E.; McKean, D. R.; Garcia, B. A. BCJ 1976, 49, 1989.
46. Staudinger, H.; Anthes, E. CB 1913, 46, 1417 (CA 1913, 7, 2576).
47. Schmidt, A. H.; Russ, M.; Grosse, D. S 1981, 216 (CA 1981, 95, 42 299w).
48. Dear, R. E. A.; Gilbert, E. E. S 1972, 310.
49. Boberg, F.; Winter, G.; Schultze, G. R. CB 1956, 89, 1160 (CA 1957, 51, 3434f).
50. (a) Djerassi, C.; Scholz, C. R. JACS 1947, 69, 2404. (b) Szabó, L.; Tóth, I.; Tőke, L.; Kolonits, P.; Szantay, C. CB 1976, 109, 3390 (CA 1977, 86, 55 266x). (c) Djerassi, C.; Scholz, C. R. JOC 1948, 13, 697.
51. Christiaens, L.; Renson, M. BSB 1970, 79, 235 (CA 1970, 73, 3726j).
52. Hevesi, L.; Sevrin, M.; Krief, A. TL 1976, 2651.
53. Semenov, V. V.; Mel`nikova, L. G.; Shevelev, S. A.; Fainzil'berg, A. A. IZV 1980, 138 (CA 1980, 92, 215 200a).
54. Volpin, M. E.; Koreshkov, Yu. D.; Dulova, V. G.; Kursanov, D. N. T 1962, 18, 107.
55. O'Connor, E. J.; Kobayashi, M.; Floss, H. G.; Gladysz, J. A. JACS 1987, 109, 4837.
56. (a) Schipper, E.; Cinnamon, M.; Rascher, L.; Chiang, Y. H.; Oroshnik, W. TL 1968, 6201. (b) Fletcher, T. L.; Pan, H.-L. JCS 1965, 4588. (c) Gilman, H.; Eisch, J. JACS 1955, 77, 3862. (d) Desmond, R.; Mills, S.; Volante, R. P.; Shinkai, I. SC 1989, 19, 379. (e) Nakao, T.; Obata, M.; Yamaguchi, Y.; Tahara, T. CPB 1991, 39, 524.
57. (a) Yusubov, M. S.; Filimonov, V. D. JOU 1989, 25, 199. (b) Yusubov, M. S.; Filimonov, V. D. JOU 1989, 25, 1410. (c) Yusubov, M. S.; Filimonov, V. D.; Ogorodnikov, V. D. IZV 1991, 868 (CA 1991, 115, 28 773w).
58. (a) Johnson, R.; Reeve, K. Spec. Chem. 1992, 12, 292. (b) Brandsma, L.; de Jong, R. L. P. SC 1990, 20, 1697.
59. (a) Fuchs, B.; Mayer, W. J. W.; Abramson, S. CC 1985, 1711. (b) Nakada, M.; Fukushi, S.; Hirota, M. BCJ 1990, 63, 944.

John E. Mills

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



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.