Halopropionates

Additions. Halogens, hydrogen haUdes, and hydrogen cyanide readily add to acryUc acid to give the 2,3-dihalopropionate, 3-halopropionate, and 3-cyanopropionate, respectively (21). 

Other Syntheses. Acryhc acid and other unsaturated compounds can also be made by a number of classical elimination reactions. Acrylates have been obtained from the thermal dehydration of hydracryhc acid (3-hydroxypropanoic acid [503-66-2]) (84), from the dehydrohalogenation of 3-halopropionic acid derivatives (85), and from the reduction of dihalopropionates (2). These studies, together with the related characterization and chemical investigations, contributed significantly to the development of commercial organic chemistry. 

Azetidones (p-lactams) are generally obtained in high yield from (3-halopropion-amides (Table 5.18) and the low yield from the reaction of N-phenyl (3-chloropropi-onamide can be reconciled with the isolation of A-phenyl acrylamide in 58% yield [34]. The unwanted elimination reaction can be obviated by conducting the cyclization in a soliddiquid system under high dilution [35, 36]. Azetidones are also formed by a predominant intramolecular cyclization of intermolecular dimerization to yield piperazine-2,5-diones, or intramolecular alkylation to yield aziridones. Aone-pot formation of azetidones in 45-58% yield from the amine and P-bromocarboxylic acid chloride has also been reported [38]. 

Acyloin-type reactions of esters provide the simplest route to 1-siloxy-l-alkoxycyclopropane [21,22] Eq. (6). The reaction of commercial 3-halopropionate with sodium (or lithium) in refluxing ether in the presence of Me3SiCl can easily be carried out on a one mole scale [21]. Cyclization of optically pure methyl 3-bromo-2-methylpropionate [23], available in both R and S form, gives a cyclopropane, which is enantiomerically pure at C-2, yet is a 1 1 diastereo-meric mixture with respect to its relative configuration at C-l Eq. (7). Reductive silylation of allyl 3-iodopropionate with zinc/copper couple provides a milder alternative to the alkali metal reduction [24] Eq. (8). 

Oxo-3,4-dihydro-2//-pyrido[l,2-ci]pyrimidines (142) and their hydrogen halide salts can be prepared by reacting 2-aminopyridine or methyl-substituted 2-aminopyridines with alkyl 3-halopropionates,20,196-200 3-halopropionic acids,200-203 or alkyl acrylates18,20 197,204 205... 

An interesting pyrolysis product of 3-chloro-2,2-bis (chloromethyl) propionic acid at 200-220 °C is 1,1-bis (chloromethyl)ethene153. This reaction may well be associated with the five-membered dehydrochlorination process of a-halopropionic acids146,147. In this respect, the HC1 elimination may be considered to proceed through a mechanism involving a six-membered transition state as described in equation 69. 

The condensation of aldehydes and ketones with ethyl chloroacetate in the presence of sodium ethoxide or sodium amide produces a,/3-epoxy esters (Darzens). The scope, limitations, typical experimental procedures, and examples have been given. Briefly, aliphatic and aromatic ketones, and aromatic aldehydes react satisfactorily, whereas aliphatic aldehydes give poor yields. a-Halopropionic and a-halobutyric... 

Aiyl esters such as those of a-halopropionic and a-halobutyric acids undergo cycloalkylation reactions, probably via preliminary Fries rearrangement to 3-halohydroxy ketones, giving the corresponding substituted indanones (equation 98). ... 

A series of a-halopropionates (1-21 and 1-22, X = Cl, Br), model compounds of the dormant polymer terminal of acrylates, are suitable for not only acrylates but also styrenes and acrylamides. Ethyl 2-chlo-ropropionate (1-21, X = Cl) was employed for the controlled radical polymerizations of MA and styrene catalyzed by CuCl/L-1 to afford relatively narrow MWDs (MwIMn 1.5).84 A better controlled polymerization of MA is achieved with the bromides 1-21 and 1-22 (X = Br) in conjunction with CuBr/L-1 to give narrower MWDs (MJMn 1.2).84 A similar result was obtained with the combination of 1-23 and CuBr/L-1 for the polymerization of styrene.166 A nickel-based system with Ni-2 and 1-21 (X = Br) gave another controlled polymerization of nBA.134 The iodide compound 1-21 (X = I) is specifically effective in conjunction with an iodide complex such as Re-1 to induce controlled polymerization of styrene.141... 

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). 

An attractive alternative to the chemistry of titanium homoenolates is the use of highly nucleophilic lanthanide homoenolates, which can be prepared by reduction of 3-halopropionates (Scheme 14). ... 

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. 

Halopropionic acid derivatives are readily accessible from lactic acid via its mesylate. Thus, treatment of 156a with AICI3 affords methyl (i )-2-chloropropionate (162) with 88% ee [59]. Reaction of 156a with KF in formamide produces methyl (R)-2-fluoropropionate (163) (96% ee). The use of formamide as solvent not only increases the reaction rate but also favors Sn2 reaction due to its high polarizability. The ti ji is approximately 30 min, and reaction is complete in 3 h [57]. (R)-2-Fluoropropionic acid is prepared from 163 by transesterification with formic acid. Amberlyst A-26 (F ) can be used as an alternate fluoride source in the conversion of mesyl lactates to chiral a-fluoroesters. This polymer-supported reagent produces clean Sn2 reactions [60]. 

The synthesis of phenoxypropionate herbicides form 2-halopropionic acids, based on the specific esterification of S-isomers with butanol catalyzed by porcine pancreatic lipase (Hasan et al. 2006)... 

The main role of the alkyl halide (RX) is to generate growing chains quantitatively. The structure of the alkyl group R preferably mimics the growing polymer chain. Therefore a-halopropionates are effective initiators for the ATRP of acrylates [288]. The main importance of the choice of the initiator for the polymerization of acrylates and methacrylates is based on the requirement of a fast initiation to obtain molecular mass control. A slow initiation results in higher moleeular masses than predicted and a higher polydispersity, which is specified in Table 9 for the polymerization of MMA [299]. Similar results were also observed for the phosphine-based Ni(II) eomplexes [301,302] and the Ni(0) complex. Here, well controlled radical polymerization was only possible with bromide initiators [303]. 

It has been published and patented that mPEG-propionic acid can be obtained by nucleophilic displacement reaction of mPEG-alkoxide with ethyl 3-bromopropionate or with halogenated 3-halopropionate substrates [78,79]. However, it was later indicated that the first method does not afford the required acid but the elimination product, due to the acid-base reaction of the hydrogen in the position a- to the carboxylic group [74]. 

The equilibrium constants increase with degree of substitution of the initiator, primary (black entries) < secondary (blue) < tertiary (red), and with the leaving atom/group, for example, for methyl 2-halopropionates, chloro bromo iodo, iodide (bottom half-filled) < chloride (open) < bromide (filled) and the presence of radical stabilizing groups for secondary initiators -COOR (squares) <-Ph (triangles) <-CN (circles) [Pg.387]

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 ). 

---