Aldol aqueous

Clalsen aldol condensation. This consists in the condensation of an aromatic aldehyde and an ester R—CHjCOOCjHj in the presence of finely divided sodium and a trace of alcohol at a low temperature. The catalyst is the alkoxide ion aqueous alkalis caimot be employed since they will hydrolyse the resulting ester. The product is an ap-unsaturated ester, for example ... 

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

The use of indium in acpieous solution has been reported by Li and co-workers as a new tool in org nometallic chemistry. Recently Loh reported catalysis of the Mukaiyama-aldol reaction by indium trichloride in aqueous solution". Fie attributed the beneficial effect of water to a eg tion phenomena in connection with the high internal pressure of this solvenf This woric has been severely criticised by... 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

As actually carried out the mixed aldol condensation product 1 3 diphenyl 2 propen 1 one has been isolated in 85% yield on treating benzaldehyde with ace tophenone in an aqueous ethanol solution of sodium hydroxide at 15-30°C... 

Cleavage reactions of carbohydrates also occur on treatment with aqueous base for prolonged periods as a consequence of base catalyzed retro aldol reactions As pointed out m Section 18 9 aldol addition is a reversible process and (3 hydroxy carbonyl com pounds can be cleaved to an enolate and either an aldehyde or a ketone... 

Acrolein reacts slowly in water to form 3-hydroxypropionaldehyde and then other condensation products from aldol and Michael reactions. Water dissolved in acrolein does not present a hazard. The reaction of acrolein with water is exothermic and the reaction proceeds slowly in dilute aqueous solution. This will be hazardous in a two-phase adiabatic system in which acrolein is suppHed from the upper layer to replenish that consumed in the lower, aqueous, layer. The rate at which these reactions occur will depend on the nature of the impurities in the water, the volume of the water layer, and the rate... 

Some unsaturated ketones derived from acetone can undergo base- or acid-catalyzed exothermic thermal decomposition at temperatures under 200°C. Experiments conducted under adiabatic conditions (2) indicate that mesityl oxide decomposes at 96°C in the presence of 5 wt % of aqueous sodium hydroxide (20%), and that phorone undergoes decomposition at 180°C in the presence of 1000 ppm iron. The decomposition products from these reactions are endothermic hydrolysis and cleavage back to acetone, and exothermic aldol reactions to heavy residues. 

Lithium Iodide. Lithium iodide [10377-51 -2/, Lil, is the most difficult lithium halide to prepare and has few appHcations. Aqueous solutions of the salt can be prepared by carehil neutralization of hydroiodic acid with lithium carbonate or lithium hydroxide. Concentration of the aqueous solution leads successively to the trihydrate [7790-22-9] dihydrate [17023-25-5] and monohydrate [17023-24 ] which melt congmendy at 75, 79, and 130°C, respectively. The anhydrous salt can be obtained by carehil removal of water under vacuum, but because of the strong tendency to oxidize and eliminate iodine which occurs on heating the salt ia air, it is often prepared from reactions of lithium metal or lithium hydride with iodine ia organic solvents. The salt is extremely soluble ia water (62.6 wt % at 25°C) (59) and the solutions have extremely low vapor pressures (60). Lithium iodide is used as an electrolyte ia selected lithium battery appHcations, where it is formed in situ from reaction of lithium metal with iodine. It can also be a component of low melting molten salts and as a catalyst ia aldol condensations. 

Class (2) reactions are performed in the presence of dilute to concentrated aqueous sodium hydroxide, powdered potassium hydroxide, or, at elevated temperatures, soHd potassium carbonate, depending on the acidity of the substrate. Alkylations are possible in the presence of concentrated NaOH and a PT catalyst for substrates with conventional pX values up to - 23. This includes many C—H acidic compounds such as fiuorene, phenylacetylene, simple ketones, phenylacetonittile. Furthermore, alkylations of N—H, O—H, S—H, and P—H bonds, and ambident anions are weU known. Other basic phase-transfer reactions are hydrolyses, saponifications, isomerizations, H/D exchange, Michael-type additions, aldol, Darzens, and similar... 

The a-ionization of 7-methylpteridines can also be utilized in aldol-type condensation reactions. 7-Methyl-pterin and -lumazine and 2,4-diaminopteridine condense readily in aqueous base with aromatic aldehydes to afford 7-alkylidenepteridines (77JOC2951). A Claisen condensation requires the protection of the acidic hydrogens of the amide bonds. 

Common impurities found in aldehydes are the corresponding alcohols, aldols and water from selfcondensation, and the corresponding acids formed by autoxidation. Acids can be removed by shaking with aqueous 10% sodium bicarbonate solution. The organic liquid is then washed with water. It is dried with anhydrous sodium sulfate or magnesium sulfate and then fractionally distilled. Water soluble aldehydes must be dissolved in a suitable solvent such as diethyl ether before being washed in this way. Further purification can be effected via the bisulfite derivative (see pp. 57 and 59) or the Schiff base formed with aniline or benzidine. Solid aldehydes can be dissolved in diethyl ether and purified as above. Alternatively, they can be steam distilled, then sublimed and crystallised from toluene or petroleum ether. 

Aldol (3-hydroxybutanal) [107-89-1] M 88.1, b 80-81 /20mm. An ethereal soln was washed with a saturated aqueous soln of NaHC03, then with water. The non-aqueous layer was dried with anhydrous CaCl2 and distd immediately before use. The fraction, b 80-81°/20mm, was collected, [Mason, Wade and Pouncy J Am Chem Soc 76 2255 1954],... 

In systems which preclude retro-aldol condensations, benzilic acid rearrangement of 11,12-diketones affords normal C-norsteroids in fair yields. For example, 11,12-diketotigogenin (82) is converted to the C-nor-(5oc,9(, 22a)-spirostane (83) in 65 % yield by barium oxide in boiling aqueous methyl-cellosolve. ... 

Isotripiperideine and a-tripiperideine structures differ from each other in a new C—C bond formed in is otripiperideine by an aldol reaction (296, 297). In aqueous media at pH 2-13, two molecules of -piperideine yield tetrahydroanabasine (297). 

The last isomer, the so-called aldotripiperideine (185), is obtained by the action of acid catalysts on a-tripiperideine at its boiling point (298,299), or in aqueous solution at pH 9.2 and 100°C. Further aldol reaction between tetrahydroanabasine and A -piperideine obviously occurs. Hydrogenolysis of this compound gives dihydroaldotripiperideine (186) which is convertible into matridine (187), a reduction product of the alkaloid matrine. 

They report that in the reaction between 5-chlorisatin 19 and 5,6-dimethoxindanone 20 under basic conditions at reflux for 16 hours, the desired quinolinic acid 22 is obtained in 38% yield with an unavoidable competing amount of the aldol product 21. However, if the same reaction is carried out using aqueous acid conditions, the quinolinic acid is obtained in a reproducible 86% yield. ... 

A conveniently short synthesis of a1prostadi1 begins with a mixed aldol assembly of the requisite cyclopentenone 13. This product is then oxidatively cleaved with periodate-permanganate and the alcohol moiety is protected as the tetra-hydropyranyl ether (14). Aqueous chromous sulfate satisfactorily reduces the olefinic linkage and the trans stereoisomer 15 predominates after work-up. The remainder of the synthesis of involves the usual steps, through 16 to with the exception that thexyl tetrahydrolimonyllithium borohydride is used to reduce the C-15 keto moiety so as to produce preferentially the desired C-15S stereochemistry. 

As shovm in Eq 6 59, Rapoport has prepared sinefungin, nucleoside andbiodcs, via nitro-aldol reaction, dehydradon, and reducdon v/iihZn in acetic acid fi-Niiro styrenes are selecdvity reduced to the corresponding oximes by indium metal in aqueous methanol under neutral conthdons ... 

Ethylhexanol is produced hy the aldol condensation of hutyralde-hyde. The reaction occurs in presence of aqueous caustic soda and produces 2-ethyl-3-hydroxyhexanal. The aldehyde is then dehydrated and hydrogenated to 2-ethylhexanol ... 

Intramolecular aldol cyclization of 2,5-heptanedione with aqueous NaOH yields a mixture of two enone products in the approximate ratio 9 1. Write their structures, and show how each is formed. 

Treatment of the minor product formed in the intramolecular aldol cyclization of 2,5-heptanedione (Problems 23.30 and 23.31) with aqueous NaOH converts it into the major product. Propose a mechanism to account for this base-catalyzed isomerization. 

The corrosion of metal surfaces and the precipitation of a metal sulfide by an aqueous acid solution can be prevented by an aldol-amine adduct. Aldol (from acetaldehyde) CH3CH(OH)CH2CHO has been utilized as a H2S scavenger that prevents the precipitation of metal sulfides from aqueous acid solutions. However, when the aldol or an aqueous solution of the aldol is stored, the solution separates quickly into two layers, with all of the aldol concentrated in the bottom layer. The bottom layer is not redispersible in the top layer or in water or acid. In addition, the aldol in the bottom layer has very little activity as a sulfide scavenger. Thus the use of aldol as a H2S scavenger in aqueous acid solutions can result in unsatisfactory results [245,247]. However, the aldol can be reacted with an amine, such as monoethanoleamine (=aminoethanol), to form an aldol-amine adduct to overcome these difficulties. The amine utilized to prepare the aldol-amine adduct must be a primary amine. The aldol-amine adduct preferentially reacts with sulfide ions when they are dissolved in the... 

The reaction of an a-halo carbonyl compound with zinc, tin, or indium together with an aldehyde in water gave a direct cross-aldol reaction product (Eq. 8.90).226,227 A direct Reformatsky-type reaction occurred when an aromatic aldehyde reacted with an a-bromo ester in water mediated by zinc in low yields. Recently, it was found that such a reaction mediated by indium was successful and was promoted by son-ication (Eq. 8.91).228 The combination of BiCl3-Al,229 CdCl2-Sm,230 and Zn-Et3B-Eb0231 is also an effective mediator. Bismuth metal, upon activation by zinc fluoride, effected the crossed aldol reaction between a-bromo carbonyl compounds and aldehydes in aqueous media. The reaction was found to be regiospecific and syn-diastereoselective (Eq. 8.92).232... 

Classical Aldol. Aldol reaction is an important reaction for creating carbon-carbon bonds. The condensation reactions of active methylene compounds such as acetophenone or cyclohexanone with aryl aldehydes under basic or acidic conditions gave good yields of aldols along with the dehydration compounds in water.237 The presence of surfactants led mainly to the dehydration reactions. The most common solvents for aldol reactions are ethanol, aqueous ethanol, and water.238 The two-phase system, aqueous sodium hydroxide-ether, has been found to be excellent for the condensation reactions of reactive aliphatic aldehydes.239... 

The Henry (nitroaldol) reaction was reported under very mild reaction conditions, in aqueous media using a stoichiometric amount of a nitroalkane and an aldehyde, in NaOH 0.025 M and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant (Eq. 8.94) 240 Good to excellent yields of (i-nitroalkanol are obtained. Under these conditions several functionalities are preserved, and side-reactions such as retro-aldol reaction or dehydration of 2-nitroalcohols are avoided. 

Base-catalyzed aldol reactions have been carried out intramole-cularly.241 The aqueous acid-catalyzed intramolecular aldol condensation of 3-oxocyclohexaneacetaldehyde proceeded diastereoselectively (Eq. 8.95).242... 

Selective retro-aldol has also been reported by using aqueous HC1 in THF.243 Recently, catalytic aldol reactions in aqueous media have generated great interest due to the atom-economy related to the reaction. Reaction of 2-alkyl-1,3-diketones with the aqueous formaldehyde using aqueous 6-10 M potassium carbonate as base afforded aldol reaction products, which are cleaved by the base to give vinyl ketones (Eq. 8.96).244... 

Lewis-Acid Catalyzed. Recently, various Lewis acids have been examined as catalyst for the aldol reaction. In the presence of complexes of zinc with aminoesters or aminoalcohols, the dehydration can be avoided and the aldol addition becomes essentially quantitative (Eq. 8.97).245 A microporous coordination polymer obtained by treating anthracene- is (resorcinol) with La(0/Pr)3 possesses catalytic activity for ketone enolization and aldol reactions in pure water at neutral pH.246 The La network is stable against hydrolysis and maintains microporosity and reversible substrate binding that mimicked an enzyme. Zn complexes of proline, lysine, and arginine were found to be efficient catalysts for the aldol addition of p-nitrobenzaldehyde and acetone in an aqueous medium to give quantitative yields and the enantiomeric excesses were up to 56% with 5 mol% of the catalysts at room temperature.247... 

Enzyme Catalyzed. The enzyme aldolases are the most important catalysts for catalyzing carbon-carbon bond formations in nature.248 A multienzyme system has also been developed for forming C-C bonds.249 Recently, an antibody was developed by Schultz and co-workers that can catalyze the retro-aldol reaction and Henry-type reactions.250 These results demonstrate that antibodies can stabilize the aldol transition state but point to the need for improved strategies for enolate formation under aqueous conditions. 

---