Sulfuric acid, with alcohols rearrangements

Sulfonimidothiazolines, 317, 318 Sulfonyl halides, with 2-aminothiazoles, 69 Sulfur (Sg), in synthesis of, A-4-thiazoline-2-thione, 373 Sulfur compounds, 69 Sulfuric acid, with alcohols, 38, 47, 80, 90 in bromination, 77 dealkylation by, 39 deuterated, 92 diazotization with, 66 in nitrations, 72 rearrangements in, 73, 113 Sulfuryl chloride, 432 Symbiotic behavior, see HSAB theory Symmetry. C2v and C2p, 120 Synthetic fibers, 154... 

This method of preparation is suitable for producing primary alkyl lactates but is unsatisfactory for /3-methallyl lactate because the strong mineral acid catalyzes the rearrangement of methallyl alcohol to isobutyraldehyde. Methyl lactate can be made conveniently (80-85% yield) by heating 1 mole of lactic acid condensation polymer with 2.5-5 moles of methanol and a small quantity of sulfuric acid at 100 for 1-4 hours in a heavy-walled bottle, such as is used for catalytic hydrogenation with a platinum catalyst. 

Because salicylic acid contains the deactivating meta-directing carboxyl group, Friedel-Crafts reactions are generally inhibited. This effect is somewhat offset by the presence of the activating hydroxyl group. Salicylic acid reacts with isobutyl or /-butyl alcohol in 80 wt % sulfuric acid at 75°C to yield 5-/-butylsalicylic acid [16094-31-8], In the case of isobutyl alcohol, the intermediate carbonium ion rearranges to (CH3)3C+. 

Rearrangements arc common in reactions of sulfur tetrafluoride with acetylenic and allylic alcohols. Highly acidic acetylenic alcohols derived from hexafluoroacetone and other haloacetones react readily at ambient temperature to give fluorinated allenes 10 as the sole... 

The methyl ester has also been obtained by esterification of cyclopentanecarboxylic acid.8 The acid, in turn, has been prepared by the Favorskii rearrangement,6 7 9-11 by the reaction of cyclopentyl Grignard reagent with carbon dioxide,12 by the carbonylation of cyclopentyl alcohol with nickel carbonyl13 or with formic acid in the presence of sulfuric acid,14 and by the hydrogenation of cyclopentene-1-carboxylic acid prepared from ethyl cyclopentanone-2-carboxylate 15 or from cyclopentanone cyanohydrin.16... 

TAFEL REARRANGEMENT. Rearrangement of the carbon skeleton of substituted acetoacetic esters to hydrocarbons with the same number of carbon atoms by electrolytic reduction to a lead cathode in alcoholic sulfuric acid. 

Rearrangements of tricyclic systems in concentrated sulfuric acid are often unlike those observed in SbFs-S02 solutions. Not only do intermolecular hydride shifts occur readily with ordinary substrate concentrations, but also the stabilities of the product alcohols control product distributions in sulfuric acid, whereas the stabilities of the carbonium ions are the controlling factors in SbFs-S02 solution. 

Which one of the following alcohols undergoes dehydration at the fastest rate on being heated with sulfuric acid (The potential for rearrangement does not affect the rate.)... 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

In the presence of base, 2-isocyanoalkanenilriles [70] react with alcohols, thiols or hydrogen sulfide to form imidazoles which have oxygen or sulfur groups in the 4(5) position. The reactions appear to proceed via the 4ff-imidazoles, which rearrange to the Iff-isomers [71]. There are similarities to the synthesis of 4-methoxyimidazole made, in 60% yield, by refluxing the Af-cyanomethylimino ester of formic acid with sodium methoxide in methanol [72]. 

The outcome of the Ritter reaction can also be determined by kinetic control. For example, conflicting reports have appeared in the literature regarding the behavior of alcohol (9), the alternative products (10) or (11) both having been reported. These differences result from the order of addition of the reagents. The amides (10) result if the alcohol is mixed first with the nitrile and acetic acid, the sulfuric acid being added last. In this instance (kinetic control), the initial cations are reacted to (10) as they are produced. Conversely, if (9) is mixed first with the acids, and then the nitrile is added, the products (11) result. In this case (thermodynamic control) cartenium ion rearrangement precedes Ritter reaction (Scheme 5). For less clear-cut cases, the use of less acidic conditions and/or lower temperature results in greater isomer selectivity, but at the cost of lower overall yields. ... 

Treatment of 3a-methoxy-2a,4a,5,7j8-tetramethyltricyclo[5.3.0.0 ]dec-5-en-4-ol with 30% aqueous sulfuric acid in hexane afforded 2a,4a,5,7 8-tetramethyltricyclo[5.3.0.0 ]dec-5-en-3-one (71) in 89% yield. This a-oxycyclopropyl alcohol to cyclobutanone rearrangement is a crucial step in the total synthesis of isocomene. 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

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