Bromoalkanoates

CYCLISATION OF POLYMETHYLENE AND POLYOXYETHYLENE CHAINS Lactonisatiort of m-bromoalkanoate anions... 

In this author s opinion, the influence of chain length on the ease of cyclisation of bifunctional chains is the most relevant and fascinating aspect in intramolecular reactions. An illustrative example is provided by the reactivity profile (Fig. 7) related to the lactonisation of co-bromoalkanoate anions (44), which is the first ring-closure reaction series for which a complete set of... 

The use of Fe, indium, and zinc as sacrificial anodes in the electrochemically assisted Reformatsky reaction of ethyl 2-bromoalkanoates with succinic anhydride is found to be effective, giving l-ethyl-3-oxohexanedioates in 49 80%... 

The lipo-amino acids are generally synthesized as racemic mixtures which are resolved into optically pure a-amino acids by chemical or enzymatic methods.113" 137 133 The synthesis is based on the alkylation of diethyl acetamidomalonate followed by hydrolysis and decarboxylation. 129 138 140 Also, 20% DMF has been used in the hydrolysis step, as it is suitable for industrial scale preparation. 138] Alternatively, lipidated a-amino acids are synthesized by reacting a-bromoalkanoic acid with ammonium hydroxide. 141 ... 

The same sequence of reactions from o-hydroxylated deoxybenzoins (250) forms 3-benzylbenzofurans, e.g., 251.584 Similarly, o-hydroxylated benzils with suitable a-bromoalkanoic esters give 3-benzoylbenzo-furans397,585 (e.g., 253, R = H).586 When R = OMe, the resulting... 

Similar phenomena are observed in electrolysis in DMF at high voltage of mixtures of alkyl 2-bromoalkanoates and succinic or glutaric anhydride8 (Equation 8.11). 

The indium-mediated Reformatsky reaction of phenyl a-bromoalkanoates with ketones or aldehydes gives di-, tri-, and tetrasubstituted /3-lactones (Table 21).327-329 A similar reaction of imines with ethyl bromoacetate gives 3-unsubstituted /3-lactams (Equation (83)).330 331... 

The efficiency of detergentless microemulsions in promoting the formation of macrocyllc lactones has been studied in our laboratoriesThe two most direct routes to the formation of large macrocyclic lactones are the acid "catalyzed esterification of ii)-hydroxyalkanoic acids and the cyclization of potassium salts of lo-bromoalkanoic acids. In both reactions a competitive pathway yields polymeric material and as a consequence high dilutions are employed with the attendant extended reaction times. 

Fig. 5. Profile of the effective molarity ( EM ) for the lactone formation from bromoalkanoates in DMSO (50 °C). The broken line shows the concentration at the start of the reaction (10 mol/l). Substrates drawn above the broken line react favourably under cyclization at the starting concentration given [102]...

Dai and co-workers [183] have reported a one-pot U-4CR followed by an intramolecular O-alkylation sequence starting from a 2-aminophenol in combination with an a-bromoalkanoic acid, an aromatic aldehyde and an isocyanide under controlled microwave irradiation. The U-4CR was carried out in MeOH and the resulting acyclic intermediate 131 was turned into the 3,4-dihydro-3-oxo-2/f-1,4-benzoxazines 132, without isolation, upon treatment with an aqueous solution of K2CO3 to promote the intramolecular 0-aUcylation in high yields (Scheme 102). 

Tellurolates can be easily alkylated and, under suitable conditions, arylated to produce symmetrical and unsymmetrical diorgano tellurium (p. 387) and alkyl aryl tellurium (p.409) compounds. Examples of alkylating agents are primary n-alkyl bromides and iodides, secondary alkyl bromides, dimethyl sulfate, allyl bromides chlorodifluoro-methane , dichloroiodomethane , methyl m-bromoalkanoates 3-halopropanoic... 

Reaction with carboxylic acids. a-Bromoalkanoic acids are obtained from the parent acids on exposure to NBS-HjSO, in trifluoroacetic acid at 85°. On the other hand, enoic acids undergo the Hunsdiecker reaction, and a catalytic version has been developed. ... 

Triphenylphosphine reacts with the methyl 2-bromoalkanoates (61) to form either the betaine (62) or the ylide (63), depending on conditions and the nature of the solvent. In the presence of aldehydes, the betaine (62) undergo Wittig reactions via the ylides (63) without the addition of base. ... 

Indium enolates, prepared conveniently by transmetalation of hfhium enolates with IriCl j, react wifh aldehydes to give fhe corresponding -hydroxy esters [80]. Ultrasound irradiation promotes fhe Reformatsky reaction of aldehydes and ethyl bromoacetate wifh indium [81]. Indium-mediated Reformatsky reaction of phenyl a-bromoalkanoates wifh ketones or aldehydes gives di-, tri-, and tetrasubstituted -lactones (Scheme 8.57) [82]. Indium-mediated reaction of imines with ethyl bromoacetate gives 3-unsubstituted -lactams (Scheme 8.58) [83]. An indium-Refor-matsky reagent prepared from 2-(chlorodifluoroacetyl)furan couples with aldehydes (Scheme 8.59) [84]. 

This simple procedure constitutes a very convenient, low-cost, and efficient synthesis of cinnamic acids. For example, reaction of a 25% MeONa in MeOH solution containing dimethyl phosphite with chloroacetic acid and then with aryl aldehydes affords (/ )-cinnamic acids in the range of 54-89%. This procedure is also apphcable to the carboxyvinylation of aldehydes or ketones with 2-bromoalkanoic acids and diethyl phosphite using NaH in DME as the base/solvent system. One of the major advantages of the overall procedure is that it avoids the need lo synthesize precursor reagents. 

Another attractive route to co-amino-(o-(hydroxycarbonyl)alkylphosphonic adds involves the use of the classical Michaelis-Arbuzov and Michaelis-Becker reactions. For example, the suitably protected 2-amino-(o-bromoalkanoates are readily converted into 3-amino-3-carboxypropylphosphonates (Scheme 8,82) ° or substituted 6-amiuo-6-c trboxyhcxylphosphonatcs by the Michaelis-Arbuzov rearrangement with trialkyl phosphites. However, it appears that, when enantiomerically pure bromide is used, the Michaelis-Arbuzov reaction is responsible for some racemization. It has been found that the extent of racemization is greater when the reaction is run at 150°C using triethyl phosphite than with trimethyl phosphite at 110°C for only the required amount of time. ... 

The aliphatic-aromatic diacid monomers were prepared from the reaction of bromoalkanoic acid methyl ester and p-hydroxy benzoic acid methyl ester. The polymers of carboxyphenoxy alkanoic add of n = 3, 5, and 7 methylenes were soluble in chlorinated hydrocarbons and melted at temperatures below 100 °C. Copolymers of these monomers melted at lower temperatures than the respective homopolymers. These polymers displayed zero-order hydrolytic degradation profile ranging from 2 to 10 weeks. Increasing the length of the alkanoic chain, decreased the degradation rate of the polymer (Fig. 3). 

If, however, 2-bromoalkanoic esters are kept for several days in an aqueous-alcoholic solution of sodium nitrite at room temperature, good yields of the... 

Liberation of amines. A modification of the classical Gabriel synthesis to gain access to a-amino acids using chiral a-bromoalkanoic esters to react with potassium phthalimide catalyzed by a chiral phase transfer agent has been reported. Unfortunately, the results are not very satisfactory. 

The Reformatsky reaction with A(-acyloxazolidin-2-ones and -thiazolidin-2-thiones provides a route to /3-keto esters. The electrolysis of a-bromoalkanoic esters in acetonitrile on a zinc anode with ZnBr2 and Bu NBEi as supporting electrolytes gives acetoacetic ester derivatives. The acetonitrile solvent is partially consumed. 

The preparation of (dialkoxyphosphinothioyl)alkanoic esters from hydrogenphosphonothioates and bromoalkanoic esters (the Michaelis-Becker alkylation reaction) has been widely used, but the use of diazoalkanoic esters is equally feasible. ... 

Reformatsky-type reaction. Using indium and iodine in DMF, the condensation of phenyl a-bromoalkanoates with carbonyl compounds leads to p-lactones. 

Reformatsky reactions. A practical synthesis of P-hydroxy-a,a-difluoroalkanoic esters involves halodifluoroacetic esters and induction by Smij. a-Bromoalkanoic esters undergo self-condensation, and if they are quenched by carbonyl compounds, 5-hydroxy-p-keto esters are formed as products. ... 

Halogenated PHAs. Several halogenated PHAs were obtained when certain bacterial species (P. oleovorans, P. putida) were cultured in media containing chlorinated, brominated or fluorinated compounds. A copolyester containing (R)-3-hydroxyoctanoate, (P)-3-hydroxy-8-chlorooctanoate, (P)-3-hydroxyhexanoate and (/ )-3-hydroxy-6-chlorohexanoate was synthesized when a culture of P. oleovorans was fed with octane and 1-chlorooctane as carbon sources (Doi and Abe 1990). Additionally, PHAs containing brominated monomers were produced by P. oleovorans when it was cultured in media containing mixtures of n-alkanoic acids (octanoic and nonanoic acids) and co-bromoalkanoic acids (Kim et al. 1992). 

Bao and coworkers [28] have reported efficient synthesis of 2H-l,4-benzoxazin-3-(4H)-ones and quinoxalin-2-(lH)-ones via domino SjjAr/copper-catalyzed coupling of ohalophenols or N-(2-halophenyl)methylsulfonamides with 2-haloamides. Dai and coworkers [29] have also developed a general base mediated synthesis of 2-alkyl-3,4-dihydro-3-oxo-2H-l,4-benzoxazine by domino Sjj condensation of 2-aminophenols with 2-bromoalkanoates under controlled microwave heating. 

Rings with more than six atoms are formed very slowly. Their formation was studied qualitatively by Ziegler and Ruzicka, and more recently Illuminati and his co-workers have published kinetic measurements for the formation of lactones from m-bromoalkanoate ions and the cycliza-tion of O-co-bromoalkoxyphenoxides. The former reactions show a rate minimum at ring sizes 7 and 8, and the rates of the latter decrease as the ring size is increased from 6 to 10. This difference in behavior is presumably related to the relative strains of these different types of ring. 

The reaction between ( )-2-bromoalkanoates and potassium phthalimide under solid-liquid phase transfer conditions using either (—)- or (-l-)-l-benzyl-cinchonidinium chloride as a chiral phase transfer catalyst gives optically active 2-phthalimido esters. ... 

---