Polyalkylated products

Pyrroles do not react with alkyl halides in a simple fashion polyalkylated products are obtained from reaction with methyl iodide at elevated temperatures and also from the more reactive allyl and benzyl halides under milder conditions in the presence of weak bases. Alkylation of pyrrole Grignard reagents gives mainly 2-alkylated pyrroles whereas N-alkylated pyrroles are obtained by alkylation of pyrrole alkali-metal salts in ionizing solvents. 

The methyl y-oxoalkanoates shown are not available by alternative methods with similar efficiency and flexibility. Although the reaction of enamines with alkyl ot-bromoacetates proceeds well in some cases, yields are only moderate in many examples.8 A further drawback is that the methods for enamine generation lack the high degree of selectivity and mildness that is characteristic of the preparation of silyl enol ethers. Related alkylations of lithium enolates often afford low yields or polyalkylated products, and are in general very inefficient when aldehydes are utilized as the starting materials.9... 

When benzene reacts with a six-fold excess of Ic in the presence of aluminum chloride at room temperature, the peralkylated product, hexakis[2-(di-chloromethylsilyl)ethyl]benzene is obtained as the major component along with other lower polyalkylated products pentakis-, tetrakis-, tris-, and bis[2-(di-chloromethylsilyl)ethyl]benzene. 

Monoalkylbenzene or other aromatic compounds react more rapidly than benzene itself in alkylation with hydrogen fluoride and the dialkyl-benzene react less rapidly in general to form tri and higher alkylated products. The polyalkylated products require more strenuous conditions. To form the monoalkyl product the alkylating agent should be added slowly to a large excess of the aromatic compound. 

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. 

Such equilibria as Fig. 5-25 allow the generation of small but controlled amounts of a free amine in solution. This effective reduction in the nucleophilicity of the co-ordinated amine may be used to good advantage. For example, the alkylation of co-ordinated amines rarely proceeds beyond the monoalkylated stage. In contrast, the reactions of the free amines usually proceed further to give a mixture of polyalkylated products (Fig. 5-26). 

The Friedel-Crafts Alkylation may give polyalkylated products, so the Friedel-Crafts Acylation is a valuable alternative. The acylated products may easily be converted to the corresponding alkanes via Clemmensen Reduction or Wolff-Kishner Reduction. 

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). 

The alkylation reaction is complicated by the occurrence of minor side reactions such as cracking, polymerization, hydrogen transfer, etc. However, of major importance is the formation of polyalKylated products. The first alkyl group formed activates the aromatic nucleus so that the second alkylation proceeds more readily than the first and so on at least until steric hindrance intervenes, although hexaethylbenzene is quite readily formed. 

Table 12.12. Polyalkylation Products from the Reaction of Toluene and Ethene...

The procedure described here illustrates a general and very convenient method to carry out the regioselective monoalkylation of ketones via their Mn-enolates. A comparison with the classical procedure previously reported by House in Organic Syntheses to prepare the 2-benzyl-6-methylcyclohexanone via the corresponding Li-enolates clearly shows that the Mn-enolate gives a higher yield of desired product since the regioselectivity is better and the formation of polyalkylated products is not observed. 

Monoalkylation of ketones. Polyalkylated products are usually obtained as by-products of attempted monoalkylation of lithium ketone enolates. Polyalkylation can be suppressed by addition of triethylboron, but this substance is spontaneously flammable. The safer boron derivative 1 is also effective, but since it is sparingly soluble in THF, DMSO is also added to the reaction. The position of alkylation can be controlled also by use of the kinetically generated enolate or the more stable equilibrium enolate. ... 

Generally, metallation occurs selectively at the less alkylated carbon. Axial methylation is highly favored no isomeric or polyalkylated products were observed in the examples cited. 

Alkylation of benzene with propene, at a 0.7 weight ratio of propene to benzene, on HZSM-5 zeolite, produces isopropylbenzene (cumene), with little formation of polyalkylated products (211). This catalyst may offer a good alternative to the supported phosphoric add actually used as catalyst. 

The fact that alkyl groups are weakly activating is why it is difficult to stop Friedel-Crafts alkylations at monoalkylation. When a first alkyl group is introduced onto an aromatic ring, the ring is activated toward further alkylation, and unless reaction conditions are very carefully controlled, a mixture of di-, tri-, and polyalkylation products is formed. Friedel-Crafts acylations, on the other hand, never go beyond monoacylation because an acyl group is deactivating toward further substitution. 

The unreacted propylene is passed on (recycled) for polymerization, the polymers formed enter the deep-cracking furnace and the dodecylene goes to the alkylation plant, as also does the benzene. Here dodecylbenzene and polyalkyl products form. The polyalkyl products are passed to the deep-cracking furnace for cracking, the unreacted benzene and dodecylene are recycled and returned for alkylation. Data concerning the alkylation of the benzene by dodecylene are given in Table 12. 

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