Carbonylation of Other Alcohols

Carbonylation of alcohols such as ethanol and -propanol with cobalt, rhodium, and iridium catalysts have also been studied. With propanol and higher alcohols, the product is found to have both the linear and the branched isomer. Thus carbonylation of n-propanol gives both butyric and isobutyric acid. In these reactions, a metal hydride intermediate such as 4.9 plays a crucial role. 

As shown by reactions 4.3.1 and 4.3.2, propylene is formed from n-proanol. It inserts into the Rh-H bond of 4.9 to give both 4.18 and 4.19. These can then undergo carbonylation to give 4.20 and 4.21, respectively. 

These two complexes are analogues of 4.8. They undergo reductive eliminations to give -butyric and isobutyric acid iodides. The two acid iodides on hydrolysis produce butyric and isobutyric acid, respectively. Although not shown here, hydrolysis of 4.20 and 4.21 (see Fig. 4.7) can also give butyric and isobutyric acid and regenerate 4.9. 

It is important to note that there are homogeneous catalytic reactions where an alkene or an alkyne is reacted with water and CO to give a carboxylic acid. As one hydrogen atom and one carboxyl group are added to the two unsaturated carbon atoms, these reactions are called hydrocarboxylation (see Section 4.6). Unlike the carbonylation 

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The RhI2(CO)2 species considered to be the active catalyst for methanol carbonylation has also been observed as the only carbonyl-containing rhodium complex during the carbonylation of other alcohols (Fig. 1 See Sections II,C and D). 

This is followed by CO insertion to give the acyl [Rh(CO)(COMe)(I)3]. In the carbonylation of other alcohols and ethylene to give carboxylic acids similar reactions occur 4... 

The reaction of alcohols with CO was catalyzed by Pd compounds, iodides and/or bromides, and amides (or thioamides). Thus, MeOH was carbonylated in the presence of Pd acetate, NiCl2, tV-methylpyrrolidone, Mel, and Lil to give HOAc. AcOH is prepared by the reaction of MeOH with CO in the presence of a catalyst system comprising a Pd compound, an ionic Br or I compound other than HBr or HI, a sulfone or sulfoxide, and, in some cases, a Ni compound and a phosphine oxide or a phosphinic acid.60 Palladium(II) salts catalyze the carbonylation of methyl iodide in methanol to methyl acetate in the presence of an excess of iodide, even without amine or phosphine co-ligands platinum(II) salts are less effective.61 A novel Pd11 complex (13) is a highly efficient catalyst for the carbonylation of organic alcohols and alkenes to carboxylic acids/esters.62... 

Our results on the catalytic conversion of other alcohols are given in Table 7. The data indicate that Co(III)-CMS4 acts as an efficient catalyst for the oxidation of other benzylic as well as secondary alcohols to the corresponding carbonyl compoimds. In the process these results compare very well with other cobalt-based catalysts [71]. 

The synthesis of succinic acid derivatives, /3-alkoxy esters, and a,j3-unsaturated esters from olefins by palladium catalyzed carbonylation reactions in alcohol have been reported (24, 25, 26, 27), but full experimental details of the syntheses are incomplete and in most cases the yields of yS-alkoxy ester and diester products are low. A similar reaction employing stoichiometric amounts of palladium (II) has also been reported (28). In order to explore the scope of this reaction for the syntheses of yS-alkoxy esters and succinic acid derivatives, representative cyclic and acyclic olefins were carbonylated under these same conditions (Table I). The reactions were carried out in methanol at room temperature using catalytic amounts of palladium (II) chloride and stoichiometric amounts of copper (II) chloride under 2 atm of carbon monoxide. The methoxypalladation reaction of 1-pentene affords a good conversion (55% ) of olefin to methyl 3-methoxyhexanoate, the product of Markov-nikov addition. In the carbonylation of other 1-olefins, f3-methoxy methyl esters were obtained in high yields however, substitution of a methyl group on the double bond reduced the yield of ester markedly. For example, the carbonylation of 2-methyl-l-butene afforded < 10% yield of methyl 3-methyl-3-methoxypentanoate. This suggests that unsubstituted 1-olefins may be preferentially carbonylated in the presence of substituted 1-olefins or internal olefins. The reactivities of the olefins fall in the order RCH =CHo ]> ci -RCH=CHR > trans-RCH =CHR >... 

Various methods of synthesis of other alcohols by reduction of carbonyl compounds are discussed in Section 16-4E. 

To date, mechanistic studies into the carbonylations of secondary alcohols with the same type of rhodium/RI catalyst system have used 2-propanol as a model substrate. At least part of the reason for this has been to minimize the expected complexities of the product analyses. The carbonylation of 2-propanol gives mixtures of n- and isobutyric acids. Two studies have been (24b, 32) reported with this system. The first of these (32) concluded that the reactivity could be described in terms of the same nucleophilic mechanism as has been described above, despite the fact that the reaction rates at 200°C were approximately 140 times faster than predicted by this type of chemistry (24b). Other data also indicated that this SN2-type reactivity was probably not the sole contributor to the reaction scheme. For example, the authors were not able to adequately explain either the effect of reaction conditions on product distribution or the activation parameters. They also did not consider the possible contribution of a hydrocarboxylation pathway, which is known to be extremely efficient in analogous systems (55). For these reasons, a second study into the carbonylation of 2-propanol was initiated (24b, 57). 

Formation of these products can be understood by assuming that the carbonylation of propargyl alcohol under high pressure involves two different reaction pathways. One is the Pd(0)-catalyzed carbonylation and the other is the Pd(II)-catalyzed oxidative carbonylation 2,3-Butadienoate (80) is a primary product of the Pd(0)-catalyzed carbonylation, but further attack by carbon monoxide at the central sp carbon of 80 under high carbon monoxide pressure yields itaconate (81) as the dicarbonylation product. Formation of aconitate (83) is explained by the oxidative dicarbonylation of a triple bond with Pd(II) species, followed by Pd(0)-catalyzed allylic carbonylation. As a supporting evidence, methyl aconitate (83) was... 

Oxidation of Other Alcohols, Glycols, Carbonyls, and Esters. The processes described for ethanol have also been found generally applicable to the oxidation of propanol and butanol to the corresponding acids, particularly those using dissolved cobalt catalysts in acid solutions. 

For the synthesis of methanol alone, contaet of the hot gases with iron should be avoided. In this case, the reactors are lined, usually with copper or some other material not affecting the catalyst. The catalysts for pure methanol are usually susceptible to iron carbonyl, formed when carbon mono-vide is in contact with iron. This impairs the activity of the catalyst or else induces undesirable side reactions. Practical operations usually involve the production of other alcohols along with methanol. In this case, a somewhat different type of catalyst is used the presence of iron is not particularly objectionable, since it also catalyzes the formation of higher alcohols from carbon monoxide-hydrogen mixtures. 

This type of oxidative addition involving the carbon-halogen bond cleavage may be involved in other catalytic processes using alcohols in the presence of hydrogen halide. For example, in the carbonylation of benzyl alcohol in the presence of HI, phenylacetic acid can be catalyfically produced in the presence of aPd(O) complex (Eq. 1.5) [25]. 

However, DPC yield and Pd turnover number (Pd TON defined as mol DPC/mol Pd charged) obtained in early works remained low. Unlike aliphatic alcohols, the oxidative carbonylation of aromatic alcohols is difficult due to their increased acidity and oxidative instability. They, therefore, require expensive catalysts [7]. It was the high cost of the optimal Pd-based catalysts, which were superior compared with all others, and low reaction rates that prevented the direct DPC process from being commercially viable. 

The great advantage of rhodium catalysts is their high selectivity, which is > 99%, based on methanol. Even in the presence of hydrogen, no hydrogenation products such as methane, acetaldehyde or ethanol are observed, in contrast to cobalt-based catalysts. In addition, the high activity allows the use of metal concentrations as low as 10 M [10]. Besides methanol, a variety of other alcohols can be submitted to the rhodium-catalyzed carbonylation and more detailed data are known for ethanol [17] and benzyl alcohol [18]. 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

Keto esters are obtained by the carbonylation of alkadienes via insertion of the aikene into an acylpalladium intermediate. The five-membered ring keto ester 22 is formed from l,5-hexadiene[24]. Carbonylation of 1,5-COD in alcohols affords the mono- and diesters 23 and 24[25], On the other hand, bicy-clo[3.3.1]-2-nonen-9-one (25) is formed in 40% yield in THF[26], 1,5-Diphenyl-3-oxopentane (26) and 1,5-diphenylpent-l-en-3-one (27) are obtained by the carbonylation of styrene. A cationic Pd-diphosphine complex is used as the catalyst[27]. 

Many of the most interesting and useful reactions of aldehydes and ketones involve trans formation of the initial product of nucleophilic addition to some other substance under the reaction conditions An example is the reaction of aldehydes with alcohols under con ditions of acid catalysis The expected product of nucleophilic addition of the alcohol to the carbonyl group is called a hemiacetal The product actually isolated however cor responds to reaction of one mole of the aldehyde with two moles of alcohol to give gem mal diethers known as acetals... 

Aldoses incorporate two functional groups C=0 and OH which are capable of react mg with each other We saw m Section 17 8 that nucleophilic addition of an alcohol function to a carbonyl group gives a hemiacetal When the hydroxyl and carbonyl groups are part of the same molecule a cyclic hemiacetal results as illustrated m Figure 25 3 Cyclic hemiacetal formation is most common when the ring that results is five or SIX membered Five membered cyclic hemiacetals of carbohydrates are called furanose forms SIX membered ones are called pyranose forms The nng carbon that is derived... 

Currently, almost all acetic acid produced commercially comes from acetaldehyde oxidation, methanol or methyl acetate carbonylation, or light hydrocarbon Hquid-phase oxidation. Comparatively small amounts are generated by butane Hquid-phase oxidation, direct ethanol oxidation, and synthesis gas. Large amounts of acetic acid are recycled industrially in the production of cellulose acetate, poly(vinyl alcohol), and aspirin and in a broad array of other... 

Catalyst recovery is a major operational problem because rhodium is a cosdy noble metal and every trace must be recovered for an economic process. Several methods have been patented (44—46). The catalyst is often reactivated by heating in the presence of an alcohol. In another technique, water is added to the homogeneous catalyst solution so that the rhodium compounds precipitate. Another way to separate rhodium involves a two-phase Hquid such as the immiscible mixture of octane or cyclohexane and aliphatic alcohols having 4—8 carbon atoms. In a typical instance, the carbonylation reactor is operated so the desired products and other low boiling materials are flash-distilled. The reacting mixture itself may be boiled, or a sidestream can be distilled, returning the heavy ends to the reactor. In either case, the heavier materials tend to accumulate. A part of these materials is separated, then concentrated to leave only the heaviest residues, and treated with the immiscible Hquid pair. The rhodium precipitates and is taken up in anhydride for recycling. 

Using only the phenyhnagnesium chloride without the MnCI catalyst results ia a mixture of products. This mixture iacludes the alcohol(s) resulting from the diaddition of the Grignard reagent to the carbonyl groups. Other catalysts, such as Fe(III) and Ni(II), have also been used to achieve similar results... 

A small amount of acetylene is used in condensations with carbonyl compounds other than formaldehyde. The principal uses for the resulting acetylenic alcohols are as intermediates in the synthesis of vitamins (qv). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

The mechanistic pattern established by study of hydration and alcohol addition reactions of ketones and aldehydes is followed in a number of other reactions of carbonyl compounds. Reactions at carbonyl centers usually involve a series of addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid-catalyzed or base-catalyzed. The rate and products of the reaction are determined by the reactivity of these tetrahedral intermediates. 

Ketonic carbonyl groups are commonly encountered in steroids and their reduction is facile, even in the absence of an alcohol. The lithium-ammonia reduction of androsta-l,4-diene-3,17-dione affords androst-4-ene-3,17-dione in 20% yield but concurrent reduction of the C-17 ketone results in formation of testosterone in 40% yield, even though the reduction is performed rapidly at —40 to —60° and excess lithium is destroyed with solid ammonium chloride. Similar reduction of the C-17 carbonyl group has been observed in other compounds. In the presence of an alcohol, a ketone is complete-... 

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