Acids aqueous acidic work

The Bucherer carbazole synthesis " involves the treatment of a naphthyl alcohol (1 or 4) or a naphthyl amine (2 or 5) with a phenylhydrazine 3 in the presence of aqueous sodium bisulfite to afford, after acidic work-up, either a benzo[a]carbazole 4 or benzo[c]carbazole 6. 

The key step in Hu s synthesis of 51 was cyclization of 50 by heating with copper(I) iodide and sodium hydride in DME, followed by a 10% aqueous ammonia work-up. Intermediate 50 was prepared via Michael addition of ethyl acetamidocyano acetate to the appropriate chalcone followed by acid-catalyzed ring closure [42,43]. 

The Merck process group subsequently published a more detailed route amenable towards multikilogram scales (Blacklock et al., 1988). This synthesis begins with treatment of alanine with phosgene to produce A-carboxyanhydride (NCA) 16 (Scheme 10.3). Under basic aqueous conditions this anhydride is coupled with proline to produce, upon acidic work-up, the dipeptide alanyl-proline (14). Enalapril is then prepared in one synthetic step by a diastereoselective reductive amination between ethyl-2— oxo-4-phenylbutyrate (13) and 14. This reaction was the subject of extensive optimization, and it was found that the highest diastereoselectivity was obtained by hydrogenation over Raney nickel in the presence of acetic acid (25%), KF (4.0 equiv.), and 3 A molecular sieves (17 1 dr). Enalapril is then isolated in diastereomerically pure form as its maleate salt (Huffman and Reider, 1999 Huffman et al., 2000). 

The initial medicinal chemistry route to the azabicyclo[3.3.0]octane-3-carboxylic acid produced the azabicyclo system in a diastereoselective but racemic manner, and required a classical resolution to achieve enantioenriched material (Teetz et al., 1984a, b 1988). Reaction of (R)-methyl 2-acetamido-3-chloropropanoate (43) and 1-cyclopentenylpyrrolidine (44) in DMF followed by an aqueous acidic work-up provided racemic keto ester 45 in 84% yield (Scheme 10.11). Cyclization of 45 in refluxing aqueous hydrochloric acid provided the bicyclic imine, which was immediately reduced under acidic hydrogenation conditions. The desired cis-endo product 46 was obtained upon recrystaUization. The acid was protected as the benzyl ester using thionyl chloride and benzyl alcohol, providing subunit 47 as the racemate. Resolution of 47 was accomplished by crystallization with benzyloxy-carbonyl-L-phenylalanine or L-dibenzoyl-tartaric acid. 

Treatment of l,l,l-trichloro-2-penten-4-one with aqueous sodium hydroxide solution gives a good yield of 5-chloro- trans-2- cis-4-pentadienoic acid after standard acid work up. 

It will not be possible to have a free OH group on the lactone during this step as the acid chloride would, of course, react there too. In practice, protection as a silyl ether (Chapter 24) was enSugh and the lithium enolate was then used for the acylation reaction. Aqueous ethanol work-up removed the silyl protection. 

The only reported example of this synthesis involved the treatment of 1,5-di-methyl-2,4-diazabicyclo[3.1.0]hexan-3-one (84) with aqueous barium hydroxide at 140°C (sealed) for 60 h, followed by an acidic work up, to give 2,2,3,5,5,6-hexam-ethyl-2,5-dihydropyrazine (85) in 42% yield, presumably via the cyclopropane derivative shown.1190... 

Enantioselective Hydrosilylation of C=N Double Bonds in Ketoximes and Ketimines. Homogeneous enantioselective hydrosilylation of prochiral alkyl aryl ketoximes has been carried out by using a Rh-(R,R)-NORPHOS catalyst. Thus, hydrosilylation of r-butyl phenyl ketoxime in the presence of [Rh(COD)Cl]2-(R,R)-NORPHOS followed by aqueous acidic work-up afforded the corresponding amine (eq 3) [16.5% ee, (5)], which became inverted to 15.0% ee (R) when this reaction was performed in the presence of added ammonium hexafluo-rophosphate (RhiNHaPF = 1.1, CH2CI2 solvent). ... 

Alkylation of potassium enolates is not always fruitful, and so counterion exchange with lithium bromide prior to addition of the electrophile has been recommended. Reduction of aromatic esters instead of acids provides a number of potential advantages. The esters tend to be more soluble than carboxylate salts, hydrogenolysis of 2-alkoxy substituents does not appear to present the s me problem, and the products are more stable. This can be important when enol ether functions are generated, allowing the necessarily acidic work-up procedures for carboxylic acids to be avoided. Indeed, the hydrolysis of enol ether functions may be very slow in aqueous acid and is best achieved through catalysis by mercury(II) nitrate. ... 

Reaction of a solution of 3a,17p-diacetoxy-ll-hydroxy-5p-androst-9(ll)-en-12-one (71) in aqueous propanol with potassium hydroxide, followed by an acidic work-up, afforded the lactone (75 76%). Three events are involved in this transformation (Scheme 16), namely retro-aldol equilibration to give the cii-fused c-o-ring system (72) - (73), stereoselective benzilic acid rearrangement (73) - (74) to... 

In this cyclic transition state, one Grignard molecule donates its alkyl group to the carbonyl carbon, while the other Grignard molecule activates this carbon by acting as a Lewis acid in complexing to the carbonyl oxygen. The resultant magnesium alkoxide is hydrolysed in the aqueous acidic work-up to yield the alcohol. 

Conventional assays in hydrochloric acid work best, if moisture is rigorously excluded. Since procyanidins are most effectively extracted with aqueous organic solvents, this is a major drawback. For this reason Makkar and Becker [143] developed a procedure which also allows the performance of the vanillin assay in aqueous methanol or acetone. The use of aqueous acetone is delicate, since it is known that acetone reacts with acidified vanillin to produce a chromogen exhibiting a A,max at 548 nm which may interfere determinations substanially [143]. 

Working forward now, here tire reasonable answers. All reactions use (Cll.>Cll2)20 as. solvent and are followed by aqueous acid work-up. 

Assume aqueous acid work-up for both this and the next problem. 

Notice that the aqueous acid work-up. necessary in the Grignard synthesis to protonate the initially formed alkoxide and convert it into the target tertiary alcohol, is also sufficient to hydrolyze the tertiary ether protecting group, releasing the primary alcohol at the end of the three-carbon chain. 

A Grignard reagent must be formed from the alkyl bromide and this must add to the ketone. Aqueous acidic work up (not mentioned in the problem as is often the case) must give a tertiary alcohol and that is biperidin. 

Azulene reacts with ethylene oxide in the presence of aluminium chloride to give, after aqueous acid work-up, 2-Cl-azulcnyl]ethanol [109]. Oxetan similarly gives 3-fl-azulenyl3propanol [109], With tetracyanoethylene oxide the major product is azulene-l-carbonyl cyanide, whose formation apparently involves cleavage of the carbon--carbon bond of the epoxide ring [110]. 

In Peterson olefination, an a-silylcarbanion is reacted with a carbonyl compound to give a / -hydroxysilane, after mild acidic work-up (e.g., with aqueous NH4CI) ... 

A special application of anion exchangers in bile acid work has resulted from the observations that many resins bind bile acids under physiological conditions (neutral pH and aqueous solutions). 

Halogens. Acidify about 2 mL of the FAQS by dropwise addition of 6 M nitric acid. Working at the hood, boil the solution gently for 2-3 min to expel any hydrogen sulfide or cyanide that may be present. Cool the solution and then add several drops of 0.3 M aqueous silver nitrate solution. A heavy precipitate of silver halide indicates the presence of chlorine, bromine, or iodine in the original organic compound. A faint turbidity of the solution should not be interpreted as a positive test. 

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