Bromoacetic add

Bromoacetic acid has been prepared by direct bromination of acetic acid at elevated temperatures and pressures,2-3-4 or with dry hydrogen chloride as a catalyst 5 and with red phosphorus as a catalyst with the formation of bromoacetyl bromide.6-7-8-9-10 Bromoacetic add has also been prepared from chloroacetic acid and hydrogen bromide at elevated temperatures 6 by oxidation of ethylene bromide with fuming nitric acid 7 by oxidation of an alcoholic solution of bromoacetylene by air 8 and from ethyl a,/3-dibromovinyl ether by hydrolysis.9 Acetic acid has been converted into bromoacetyl bromide by action of bromine in the presence of red phosphorus, and ethyl bromoacetate has been... 

Scheme 16 shows a synthesis of regioisomeric 2,6-diketopiperazines 59. Wang-resin-linked bromoacetic add 56 was reacted with 4-nitrobenzyl esters of amino... 

Scheme 4.7 Synthesis of zwitterionic ILBSs, from Af-alkyUmidazole and bromoacetic add. Source Wang et aL [21, 22] and reproduced with permission from Elsevier and ACS, respectively.

The Reformatsky Reaction consists of the interaction of an ester of an a-halogeno-acid with an aldehyde, a ketone or another ester in the presence of zinc. For example, if a mixture of ethyl bromoacetate and benzaldehyde is heated with zinc, the latter undoubtedly first combines with the ethyl bromoacetate to form a Grignard-like reagent (reaction A), which then adds on to the benzaldehyde Just as a Grignard reagent would do (reaction B). The complex so formed, on acidification gives ethyl p-phenyl-p-hydroxy-propionate (reaction C). Note that reaction A could not satisfactorily be carried out using... 

The iron slurries react readily with ethyl a-bromoacetate. The resulting organoiron species adds readily to aldehydes and ketones to produce 3 -hydroxyesters in excellent yields. Addition of a mixture of an aryl aldehyde and an allylic halide to the iron slurry produced good yields of the cross-coupled alcohol. 

REFORMATSKY REACTION. Dating back to 1887, this reaction depends on interaction between a carbonyl compound, an a-halo ester, and activated zinc in the presence of anhydrous ether or ether-benzene, followed by hydrolysis. The halogen component for example ethyl bromoacetate, combines with zinc bo form an organozinc bromide that adds to the carbonyl group of the second component to give a complex readily hydrolyzed to carbinol. The reaction... 

Dissolve bromoacetic acid (10 eq, relative to resin loading) and DIC (11 eq) in minimal amount of DMF. Add this solution to the resin. 

Add the mixture of ethyl bromoacetate and cyclohexanone dropwise using a cannula to the stirring slurry of active zinc over a 30 min period. 

Charge the flask with zinc dust (6.54 g, 100 mmol) and CuCI (990 mg, 10 mmol), add anhydrous THF (20 mL), and reflux the suspension for 30 min. During this activation period, charge the dropping funnel with ethyl bromoacetate (4.18 g, 25 mmol) and THF (10 mL). 

Discontinue the heating. Add ca. 1/10 of the bromoacetate solution at once to the stirred Zn(Cu) couple while still hot. When the Reformatsky reaction gets started, the suspension becomes turbid and the solvent begins to boil. Add the rest of the content of the dropping funnel to the suspension in such a rate as to maintain a gentle reflux (ca. 15 min). 

Carbon-carbon bond formation reactions with peroxides are quite limited, in view of the synthetic features. However, the following atom-transfer reaction may be useful. Treatment of iodomethyl phenyl sulfone (45) with benzoyl peroxide generates an electrophilic benzenesulfonylmethyl radical, which adds to electron-rich 1-hexene to give the addition product (46) (eq. 4.18) [49-51]. The same treatment of bromoacetic acid and 1-hexene with benzoyl peroxide affords 7-butyl-7-lactone through the cyclization of the formed 7-bromoctanoic acid. 

For Cys-terminated PNA, carry out the final coupling with Boc-Cys(Npys)-OH. Do not carry out a subsequent Fmoc deprotection step. For A -bromoacetyl PNA, carry out Fmoc deprotection followed by the final coupling as follows. Dissolve bromoacetic acid (2 mmol) in dichloromethane (5 mL) and add diisopropylcar-bodiimide (2 mL, 0.5 M). Stir for 15 min and filter off the white precipitate (diisopropylurea) and evaporate the filtrate to approx. 2.5 mL. Adjust the volume to 6 mL with DMF and evaporate to approx. 4 mL by bubbling Argon gas through the solution. Filter the solution a second time. Use the resultant bromoacetic anhydride in DMF for coupling to the support. 

Bromoacetate is an excellent electrophile for Sn2 reactions so some of the pyridine rings in the polymer displace bromide and form a neutral functionalized polymer. Protonation gives the free add. 

As a synthetic route, this organoborane synthesis parallels the aoetoaoetic ester and malonic ester syntheses. An acetone unit is furnished by acetoacetic ester or, here, by bromoacetone an acetic add unit is furnished by malonic ester or, here, by bromoacetic ester. In these syntheses, bromine plays the same part that the —COOEt group did by increasing the acidity of certain a-hydrogens, it determines where in the molecule reaction will take place it is easily lost from the molecule when its job is done. Unlike the loss of —COOEt, the departure of —Br is an integral part of the alkylation process. 

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