Phenylethyl halides

Controlled polymerization requires that the initiation rate is at least comparable to that of propagation. Initiation in controlled/living carbocationic systems is usually carried out using models of growing species in their dormant state (e.g., the adducts of a monomer with protonic acids). This enables a similar set of equilibria to be established between carbocations and dormant species for initiation and for propagation. For example, 1-phenylethyl halides have similar reactivity as the macromolecular dormant species in styrene polymerizations, and I-alkoxyethyl derivatives are as reactive as the macromolecular species in the polymerization of vinyl ethers [Eq. (38)] ... 

One can conclude that the 1-phenylethyl halide is by far the preferred product of these interactions, but that suitable conditions of polarity and temperature can create the conditions required for some polymerisation to take place. Pocket et al. have demonstrated that 1-phenylethyl chloride exchanges chlorine atoms with HCl in nitromethane, i.e., that carbenium ion pairs can be generated in tiiis system. It seems likely that the low yields of polymers observed in specific conditions as described above resulted from the solvation of the halide by excess acid, a contingency which restricted active species to a short period. From the few scattered results published it is nevertheless difficult to derive a sound interpretation of such apparent anomalies as the fact that the strongest of all hydrogen halides, HI, failed to induce polymerisation. 

Phenylethyl halides (1-13, X = Cl, Br, I), adducts of styrene and the corresponding hydrogen halide, can be considered as a unimer of the dormant C—X terminal of polystyrene, and thus they are particu-... 

In the mechanistic study of metal-catalyzed living polymerization, this method has thus far been utilized primarily for analysis of model reactions to uncover the interaction between a metal catalyst and a carbon—halogen dormant end.170 176 Typical models for the dormant end include a-haloesters, such as alkyl haloisobutyrate and MMA dimer halides 1-25 (Figure 8) (for methacrylate), alkyl 2-halopropionate (for acrylate), and a-phenylethyl halide (for styrene). 

The halogen end group can be transformed into other functionalities by means of standard organic procedures, such as a nucleophilic displacement reaction. Different authors have investigated this process of the nucleophilic displacement reactions with model compounds, to confirm the feasibility and selectivity. Compounds such as 1-phenylethyl halide, methyl 2-bromopropionate, and ethyl 2-bromoisobutane mimic the end groups of PSs, poly(alkyl acrylates), and poly(alkyl methacrylates), respectively. Different compounds have been tested, such as sodium azide, n-butylamine, and n-butylphosphine. 

PhEtX = 1-phenylethyl halide, MeXPr = methyl 2-halopropionate The value in parentheses is the ratio of Katrp of the alkyl bromide to its chloride analogue. 

It is believed that this reaction proceeds via initial formation of hydrochloric salts of imidoyl chloride when POCI3, PCI5, or SOCI2 is used as a reagent, followed by the formation of imidoyl chloride by the loss of hydrogen chloride, which is in equilibrium with nitrilium salt. Then the 3,4-dihydroisoquinoline is formed via the ring closure of nitrilium salt, as indicated in the direct formation of such dihydroisoquinoline via alkylation of nitrile with phenylethyl halide in the presence of a Lewis acid. An exemplary mechanism of the Bischler-Napieralski reaction is illustrated here. 

Of particular relevance to ATRP are alkyl halides that structurally resemble the halogen-terminated polymer chains, i.e., the dormant species. Some of these alkyl halides (see Figure 8.5) include 1-phenylethyl halides (1-PhEtX), 2-halopropionate esters (R-XP, where R = alkyl or aryl), 2-halopropionitriles (XPN), and 2-haloisobutyrate esters (R-XiB, R = alkyl or aryl) that mimic the chain ends of halogen-capped polystyrenes, polyacrylates, polyacrylonitrile, and polymethacrylates, respectively (in all cases, X = C1, Br). Some other important initiators include methacrylate-type dimers ((R-MA)2X, which are better models of X-capped polymethacrylates than R-XiB), arenesulfonyl halides (ArS02X, e.g., 4-methylbenzenesulfonyl (tosyl) chloride, which is often used in the polymerization of methacrylates and acrylonitrile ), 2-halophenylacetate esters (R-XPA), and 2-halo-2-methylmalonate esters (RR XMM, suitable in the polymerization of methacrylates under low-catalyst-concentration conditions ). 

Out of the above the P elimination is most common. These eliminations result in the formation of alkenes and alkynes. When P phenylethyl bromide is heated with an alcoholic solution of an alkali first a carbanion is formed by the loss of a proton followed by the loss of a halide ion and simultaneous formation of a double bond. 

The opposite of the stabilisation of an ester is its activation. If we include in the concept ester the alkyl halides, their Friedel-Crafts reactions provide familiar examples of this phenomenon. An unusual example especially relevant to our present considerations is provided by some results made available to me in advance of publication by Giusti and Andruzzi. Their results [38] on the polymerisation of styrene by iodine and hydrogen iodide can be interpreted in terms of an organic iodide derived from styrene, probably 1-phenylethyl iodide, being activated by the co-ordination of one or two molecules of iodine. This process appears to polarise the C—I bond to such an extent that the normally stable ester becomes activated to a chain-propagating species and induces a pseudocationic polymerisation ... 

When treated with a strong base such as butyllithium or potassium tert-butoxide, 2-isocyano-tV[(S)-l-phenylethyl]propanamide (1) forms an enolate 2 which is not alkylated at low temperatures. Instead it rearranges on warming and cyclizes to give the enolate of 3,5-dihydro-5-methyl-3-[(,3 )-1-phenylctbylJ-4//-imidazol-4-onc (3) which can be alkylated with benzylic halides with excellent diastereoselectivities4,13. 3-Halopropenes or haloalkanes give much lower diastereoselectivities. 

Asymmetric coupling of a vinyl halide with a Grignard reagent. 1-Phenylethyl-magnesium chloride couples with vinyl bromide in the presence of a nickelcatalyst (1) composed of NiCl, and (-)-norphos to give (S)-3-phenyl-l-butene (2) in 67% enantiomeric excess.1... 

Ifebls 1 Relative Rates of Solvolysis of 1-Phenylethyl Esters and Halides... 

Most stereoselective alkylations to the lactone intermediates are accomplished using the method reported by Kleinman and co-workers.1201 The dianion form is prepared by treating the lactone with lithium or sodium hexamethyldisilanazide. Then, the reaction between the dianion and an alkyl halide produces the 2-alkylated lactone (Scheme 11, Section 10.6.2). Kleinman and co-workers reported that the ratio of the trans- and ds-lactone is 47 3. When a doubly protected a-amino aldehyde [e.g., dibenzylamino aldehyde, (/ert-butoxycarbonyl)-benzylamino aldehyde] is used, the c/.v-lactone is not obtained. As an example, the alkylation of (55,1 5)-5-[l -[/V-(/< rt-butoxycarbonyl)benzylamino]-2 -phenylethyl]dihydrofuran-2(3/7)-one to produce (3/ ,55,l 5)-3-benzyl-5-[1 -[/V-(/ert-butoxycarbonyl)benzylamino]-2 -phenyl-ethyl]dihydrofuran-2(3//)-one is described in this section. 

When the halogen substituent is located two or more carbons from the aryl group as in 2-phenylethyl bromide, C6H5CH2CH2Br, the pronounced activating effect evident in benzylic halides disappears, and the reactivity of the halides is essentially that of a primary alkyl halide (e.g., CH3CH2CH2Br). 

Generation of an a-silylallenic zinc and its reaction with an acyl halide synthesis of 6-(dimethylphenylsilyl)-2,2-dimethyl-4-(2-phenylethyl)-5-hexyn-3-one (Structure 33)11... 

The presence of an aryl group at the /7-carbon atom of an alkyl halide influences both its photochemical behaviour and its photoreactivity (for reviews, see Section VII of Reference 11 and Reference 12). The irradiation of 2-phenylethyl bromide and iodide (40) in nucleophilic solvents such as methanol (equation 44)64 yields simpler and different product mixtures than those of 1-bromo- and 1-iodooctane, described in equation 325 in Section II. A. The only ion-derived product is 41, while for the 1-halooctanes the main ionic... 

First-Order Reactions First-order nucleophilic substitution requires ionization of the halide to give a carbocation. In the case of a benzylic halide, the carbocation is resonance-stabilized. For example, the 1-phenylethyl cation (2°) is about as stable as a 3° alkyl cation. 

Boron trichloride and tribromide exchange ligands when used with alkyl halides and acetates initiators. For example, as shown in Eq. (35), 1-phenylethyl bromide and BBr2Cl are formed rapidly and quantitatively when 1-phenylethyl chloride is mixed with an equimolar amount of boron tribromide [59,67]. 

The rates of initiation and propagation are comparable when the covalent initiator and dormant chain ends have similar structures. Therefore, 1-phenylethyl precursors are useful initiators for styrene polymerizations, but are poor initiators for a-methylstyrene and vinyl ether polymerizations. Similarly, cumyl derivatives are good initiators for isobutene and styrene, but are poor initiators for vinyl ethers their initiation of a -methylstyrene is apparently slow [165]. 1-Alkoxyethyl derivatives are successful initiators for vinyl ethers, styrenes, and presumably isobutene polymerizations [165,192]. /-Butyl derivatives initiate polymerization of isobutene slowly [105]. This is mirrored in model studies that show that /-butyl chloride undergoes solvolysis approximately 30 times slower than 2-chloro-2,4,4-trimethylpentane [193]. This may be due to insufficient B-strain in monomeric tertiary precursors [194]. In contrast, monomeric and dimeric or polymeric structures of secondary esters and halides apparently have similar reactivity. 

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