1- Bromopropane alkylation using

Friedel-Crafts alkylation has the problem of cation rearrangement, but there is another problem with this reaction. When benzene reacts with 2-bromopro-pane and AICI3, it gives a mixture of 53 (1-methylethylbenzene or isopropylbenzene, also known as cumene), which is the expected product however, it also gives the disubstituted product 54. The latter may be the major product if an excess of 2-bromopropane is used. Therefore, the reaction with alkyl halides may lead to polyalkylation of the benzene ring, which is the second of the two problems noted for Friedel-Crafts alkylation. The only way to explain formation of 54 is via a Friedel-Crafts alkylation of the initially formed product 53 with 2-bromopropane. This result suggests that 53 must react more quickly with the carbocation derived from 2-bromopropane than does benzene. This point will be discussed in more detail later. 

Alkylation of phenothiazine with l-chloro-2-methyl-3-bromopropane affords the methylated analog (80) of the intermediate above. Use of this halide to alkylate the piperazine... 

A series of benzimidazole and benzimidazolone derivatives from the Janssen laboratories has provided an unusually large number of biologically active compounds, particularly in the area of the central nervous system. Reaction of imidazolone itself with isopropenyl acetate leads to the singly protected imidazolone derivative 51. Alkylation of this with 3-chloro-l-bromopropane affords the functionalized derivative Use of this... 

Strategy Compare the product with the starting material, and catalog the differences. In this case, we need to add three carbons to the chain and reduce the triple bond. Since the starling material is a terminal alkyne that can be alkylated, we might first prepare the acetylide anion ol 1-pentyne, let it react with 1-bromopropane, and then reduce the product using catalytic hydrogenation. 

Some data on the alkylation of naphthalene by 2-bromopropane using A1C13 under different conditions are given below. What factors are responsible for the differing product ratios for the two solvents, and why does the product ratio change with time ... 

It would not work to use propyne and 2-bromopropane for the alkylation step of... 

An early synthesis of A5-palmitoy]-.S -[2,3-bis(palmitoyloxy)propyl]cysteine employed cysteine methyl ester, however, this leads to difficulties in the saponification step of the tri-palmitoylated residue. 96 The optimized procedure, in which the cystine di-fert-butyl ester is used, 90 is outlined in Scheme 6 after N-acylation with palmitoyl chloride, the ester is reduced to the cysteine derivative for S-alkylation with l-bromopropane-2,3-diol to yield chirally defined isomers if optically pure bromo derivatives are used. Esterification of the hydroxy groups is best carried out with a 1.25-fold excess of palmitic acid, DCC, and DMAP. The use of a larger excess of palmitoyl chloride is not recommended due to purification problems. The diastereomeric mixture can be separated by silica gel chromatography using CH2Cl2/EtOAc (20 1) as eluent and the configuration was assigned by comparison with an optically pure sample obtained with 2R)- -bromopropane-2,3-diol. 

Rutherford [43] reports the use of the modified Rackett equation to correlate the density for alkyl chlorides (1-chloroethane, 1-chloropropane, and 1-chlorobutane) and bromides (bromomethane, bromoethane, and bromopropane) as a function of temperature, pressure, and critical point data. 

There are two ways of naming alkyl halides. The systematic (IUPAC) nomenclature treats an alkyl halide as an alkane with a halo- substituent Fluorine is fluoro-, chlorine is chloro-, bromine is bromo-, and iodine is iodo-. The result is a systematic haloalkane name, as in 1-chlorobutane or 2-bromopropane. Common or trivial names are constructed by naming the alkyl group and then the halide, as in isopropyl bromide. This is the origin of the term alkyl halide. Common names are useful only for simple alkyl halides, such as the following ... 

Solution First alkylate the acetylide anion of 1-pentyne with 1-bromopropane to add three carbons, and then reduce the product using catal3rtic hydrogenation j... 

Use SpartanView to examine the electrostatic potential map of the acetylenic ether shown below. A.ssuming that the most positive hydrogen is also the most acidic, what product would be obtained from treatment of the compound with NaNH2 to form an anion, followed by alkylation with 1-bromopropane ... 

Acetylide ion alkylation is an Sn2 reaction, and it s therefore understandable that only primary alkyl halides and tosylates react well. Since acetylide anion is a strong base as well as a good nucleophile, E2 elimination competes with Sn2 alkylation when a secondary or tertiary substrate is used. For example, reaction of sodio ]-hexyne with 2-bromopropane gives primarily the elimination product rather than the substitution product ... 

If two sets of reagents are available for the synthesis of an alkene, it is better to use the one that requires the less sterically hindered alkyl halide for synthesis of the ylide. Recall that the more sterically hindered the alkyl halide, the less reactive it is in an Sn2 reaction (Section 10.2). Eor example, it is better to use a three-carbon alkyl halide and a five-carbon carbonyl compound than a five-carbon alkyl halide and a three-carbon carbonyl compound for the synthesis of 3-ethyl-3-hexene because it would be easier to form an ylide from 1-bromopropane than from 3-bromopentane. 

SOLUTION TO 34b (1) The alkyl halide required depends on which phosphonium ylide is used it would be either 1-bromobutane or 2-bromopropane. 

B.ii. Isomerization. There are several problems associated with Friedel-Crafts alkylation. The first occurs when primary and secondary halides are used, because the cations formed from these substrates are subject to rearrangement. Reaction of benzene with 1-bromopropane and aluminum bromide (AlBr3), for... 

Simple reagents (e.g., 2-bromopropane) can be used with success, and the advantage is essentially convenience.154,255 With benzylic halides, the utility appears more clearly, since the preparation of the corresponding organometallic is sometimes difficult.256 With a-enones, only 1,2-addition occurs.257 Long-chain fatty alkyl halides, which react sluggishly with metals, also provide satisfactory results.258 Allylic phosphates can be used as a source of allyl anions 259... 

If you want to synthesize an alkene, you should choose the most hindered alkyl halide possible in order to maximize the elimination product and minimize the substitution product. For example, 2-bromopropane would be a better starting material than 1-bromopropane for the synthesis of propene because the secondary alkyl halide would give a higher yield of the desired elimination product and a lower yield of the competing substitution product. The percentage of alkene could be further increased by using a sterically hindered base such as f rf-butoxide ion or DBN instead of hydroxide ion (Section 10.10). 

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