And polyalkylation

Deall lation, Transall lation, and Disproportionation. The action of aluminum chloride also removes alkyl groups from alkylbenzenes (dealkylation, disproportionation) (12). Alkylbenzenes, when heated with AlCl, form mixtures of benzene and polyalkylated benzenes ... 

Rhodium catalyzed carbonylations of olefins and methanol can be operated in the absence of an alkyl iodide or hydrogen iodide if the carbonylation is operated in the presence of iodide-based ionic liquids. In this chapter, we will describe the historical development of these non-alkyl halide containing processes beginning with the carbonylation of ethylene to propionic acid in which the omission of alkyl hahde led to an improvement in the selectivity. We will further describe extension of the nonalkyl halide based carbonylation to the carbonylation of MeOH (producing acetic acid) in both a batch and continuous mode of operation. In the continuous mode, the best ionic liquids for carbonylation of MeOH were based on pyridinium and polyalkylated pyridinium iodide derivatives. Removing the highly toxic alkyl halide represents safer, potentially lower cost, process with less complex product purification. 

Figure 44.1. Conversion of phenol ( ), selectivity to o-cresol (O), 2,6-xylenol (O), p-cresol (A), anisole (X), 2,4-xylenol ( ) and polyalkylated phenols ( ) as...

At low temperature, an almost equimolar amount of m-cresol and of DMAs were produced (selectivity of 41% and 32%, respectively), with minor amounts of DMPs. Therefore, it is likely that the primary mechanism for the transformation of 3-MA consists of the intermolecular methylation with cogeneration of m-cresol and DMA. Also, the contribution of hydrolysis of 3-MA to yield m-cresol can not be excluded. On increasing the reaction temperature, the selectivity to DMAs decreased, with a corresponding increase in the formation of DMPs and polyalkylates. This is likely due to the reactions between DMAs and m-cresol to yield DMPs, and between two molecules of DMAs (a sort of intermolecular disproportionation) to yield polyalkylates and DMPs. The selectivity to m-cresol remained approximately constant on increasing the reaction temperature. 

The reaction pathway for the gas-phase methylation of m-cresol, as inferred from catalytic data here reported, can be summarized as shown in Scheme 1. Methanol and m-cresol react through two parallel reactions, yielding either 3-MA or DMPs. The relative contribution of the two reactions is a function of the physico-chemical features of the catalysts, and of the reaction temperature as well, C-methylation being kinetically favored at high temperature. Consecutive reactions occur on 3-MA, which acts as a methylating agent yielding DMPs, DMAs and polyalkylates (with co-production of m-cresol in all cases) by reaction with m-cresol, 3-MA and DMPs, respectively. Consecutive reactions may also occur on DMPs to yield polyalkylates. 

In light of these significant challenges, Evans and Leahy reexamined the rhodium-catalyzed allylic alkylation using copper(I) enolates, which should be softer and less basic nucleophiles [23]. The copper(I) enolates were expected to circumvent the problems typically associated with enolate nucleophiles in metal-allyl chemistry, namely ehmina-tion of the metal-aUyl intermediate and polyalkylation as well as poor regio- and stereocontrol. Hence, the transmetallation of the lithium enolate derived from acetophenone with a copper(I) hahde salt affords the requisite copper] I) enolate, which permits the efficient regio- and enantiospecific rhodium-catalyzed allylic alkylation reaction of a variety of unsymmetrical acychc alcohol derivatives (Tab. 10.3). 

Di- and polyalkylation can occur during alkylation with alkyl halides since the product alkylbenzenes are more reactive, although the reactivity difference with reactive alkylation systems is small. Toluene, for example, reacts only about 2-5 times faster in some benzylations than benzene.118,119 As alkylbenzenes, however, dissolve preferentially in the catalyst containing layer, heterogeneous systems can cause enhanced polysubstitution. The use of appropriate solvents and reaction conditions as well as of an excess of aromatics allow the preparation of monoalkyl-ated products in high yields. 

In alkylation of benzene with both ethylene and propylene di- and polyalkylates are also formed. In alkylation with propylene 1,2,4,5-tetraisopropylbenzene is the most highly substituted product steric requirements prevent formation of penta-and hexaisopropylbenzene. On the other hand, alkylation of benzene with ethylene readily even yields hexaethylbenzene. Alkylation with higher alkenes occurs more readily than with ethylene or propylene, particularly when the alkenes are branched. Both promoted metal chlorides and protic acids catalyze the reactions. 

The benzenoid C-l resonance of styrene units in acrylonitrile-styrene copolymers is particularly sensitive to the sequence of the chain relative configurations of triad sequences can be determined by quantitative evaluation of carbon-13 signals [524], Micro-structures of other vinyl polymers such as polystyrene [525], polypropylene oxide [526], and polyalkyl acrylates [527] have also been investigated by 13C NMR. 

Under the same conditions simple etiolates react vigorously with alkyl halides (which must be primary) to give mono- and polyalkylated products. The reactivity of the simple enolate is greater and cannot be controlled at room temperature. However, if the alkylation is carried out at low temperature, the reaction can be controlled and smooth monoalkylation of simple enolates can be achieved. The same is true for the alkylation of acetylide anions, which must be carried out at low temperature for successful alkylation. 

The Sn2 reaction of amines with alkyl halides is complicated by a tendency for overalkylation to form a mixture of monoalkylated and polyalkylated products (Section 19-11). Simple primary amines can be synthesized, however, by adding a halide or tosylate (must be a good SN2 substrate) to a large excess of ammonia. Because there is a large excess of ammonia present, the probability that a molecule of the halide will alkylate ammonia is much larger than the probability that it will over-alkylate the amine product. 

So far only the p-f-butylcalix[6]arene 2 has been symmetrically alkylated in the 1,3,5-positions, using K2C03 as a base and relatively few alkylating agents.20,21 The reaction is not very selective and a mixture of mono- and polyalkylated products are obtained from which 1,3,5-trialkoxy-p-f-butyl-calix[6]arenes may be isolated by flash chromatography. The yields are modest and range between 15 and 27% (Scheme 7.6). 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

Friedcl-Crafts alkylation of naphthalene is of little use, probably for a combination of reasons the high reactivity of naphthalene which causes side reactions and polyalkylations, and the availability of alkylnaphthalenes via acylation or ring closure (Sec. 30.14). 

Prior to the discoveries that lithium and other less electropositive metal cations were valuable counterions for enolate alkylations, the Stork enamine reaction was introduced to overcome problems such as loss of regioselectivity and polyalkylation that plagued attempts to alkylate sodium or potassium enolates of ketones or aldehydes.Methods of synthesis of enamines by reactions of ketones and aldehydes with secondary amines have been thoroughly reviewed.Enamine alkylations are usually conducted in methanol, dioxane or acetonitrile. Enamines are ambident nucleophiles and C- and V-alkylations are usually competitive. Subsequent hydrolysis of the C-alkylated product (an iminium salt) yields an... 

Aromatic Aldehydes. The preparation of aromatic aldehydes from benzene or monoalkyl and polyalkyl aromatic compounds by means of carbon monoxide and hydrogen chloride has been reviewed by Crounse (19). 

A variety of approaches has been adopted in the following methods which involve comparatively unusual and neglected routes to phenols. Syntheses described in this section have been employed to obtain cycloaromatic structures and bicyclic heterocyclic compounds containing the phenolic group. Methods involving the use of noble and transition metal compounds have invariably produced polyalkylphenols and these procedures are more appropriately considered in Chapter 6 although it is clear that there is a considerable overlap between the synthesis of monoalkylphenols and polyalkyl compounds. 

Prolonged exposure of 167 to aluminum chloride also gives product 172 via 171, which is a thermodynamic process that favors the most stable isomer, and polyalkylation is also possible. Exposure of sec-butyl-benzene (173) to the mixed-acid HF—BF3 led to a mixture of 36.7% of benzene, 10.9% of n-butylbenzene, 21.8% of scc-butylbenzene, and 30.6% of di-scc-butylbenzene. Similarly, when n-butylbenzene was heated with aluminum chloride (100°C, 3 h), 45.2% of butylbenzene (99.4% n-butylbenzene and 0.6% sec-butyl-benzene), 15.2% of benzene, and 27.7% of dibutylbenzene (>90% meta) along with 11.9% of polyalkylated benzene products were obtained.lO Lewis acid induced isomerization of dialkylbenzenes usually leads to an increase in the relative percentage of meta isomer, as seen with n-butylbenzene, based on the greater thermodynamic stability of the meta product than that of the ortho and para products. ... 

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