Halo acids formation

An interesting C-S bond formation mediated by benzyltriethylammonium tetrathiomolybdate converts -halo acid chlorides into thiolactones [64] (Scheme 4.16). 

The second method of intramolecular cyclization to 2,5-DKPs involves formation of the Ni—Ce bond. This reaction entails acylation of glycinamide with an a-halo acid halide, followed by ring closure under basic conditions. ... 

Dimerization of tetraacetylethylene (18) has led to spirofuran (19), whose structure was established by X-ray analysis (80CJC1645). A possible mechanistic pathway for its formation would involve the dimerization of an intermediate (20) which could account for the stereochemistry of the dimer (19) (Scheme 4). The same furan (21) is a possible intermediate in the formation of 3,4-diacetyl-2-halomethyl-5-methylfuran (22) from (18) with concentrated halo acids (70JCS(C)1536). The structures of the furans (22) were established by chemical and spectroscopic methods. 

Results of a kinetic study of the formation of phthalide by dehydrobromination of a-bromo-o-toluic acid are believed to provide support for an intimate ion-pair mechanism for the pyrolysis of some types of halo acids in the gas phase.51... 

Cyclization occurs directly through catalysis by the acid liberated when a pyridine-2(lH)-thione is heated with an a-halo acid ester. The most convenient method for preparing the thiazole, however, seems to be the cyclization of (2-pyridinethio)acetic acids in acetic anhydride in the presence of pyridine. Without base catalysis the reaction is slow, which suggests a mixed anhydride intermediate. Mixed anhydride formation with ethyl chlorofor-mate in pyridine, or carboxyl activation by DCC in pyridine, gives the mesoionic product. The cyclization reaction and the chemical stability of the thiazole are adversely affected by a pyridine 6-substituent. The initially formed acylpyridinium salt (407) undergoes rapid tautomerization to the aromatic thiazole form equilibrium between the forms (407) and (408) is verified by rapid deuteration at C-2 (R1 = H) in AcOH-d (81H(15)1349). 

A frequent theme in alcohol carbonylations by transition metals is the use of a halide or pseudo-halide promoters or cocatalysts. Despite major problems of corrosion associated with its use, iodide is almost always found to be most effective in this capacity. This is because the halide serves several purposes, for each of which iodide is ideally suited. One of the most important roles of these anion promoters can be that of facilitating the formation of metal-carbon bonds via the formation of intermediate alkyl halides. Under typical catalytic conditions for a variety of systems, at least some portion of the added halide is converted to the corresponding strong halo-acid. In fact, conditions are generally set so that this event is maximized. 

The exchange of halogen for the amino group is important in the formation of other polyfunctional compounds, particularly the amino acids. In several of these transformations with aqueous or liquid ammonia, it has been shown that the presence of ammonium salts minimizes the formation of secondary and tertiary aminesExcellent directions for the synthesis of a-amino acids (C,-C ) from a-halo acids and ammonia are given. The methods have been reviewed. Long-chain amino acids are prepared by this and other procedures. ... 

Several variations of this reaction are possible. The halo acid is boiled with a solution of sodium in absolute alcohol as in the formation of y-bu-tyrolactone (67%), or the dry sodium salt of a halo acid is heated under vacuum as in the preparation of 8-valerolactone (30%). The corresponding esters are sometimes refluxed with alcoholic potassium hydroxide or decomposed thermally at 15 180° whereby a molecule of an alkyl halide is eliminated. The latter process is valuable in making a-alkyl-y-lac-tones of higher-molecular-weight acids since the y-bromo esters are available by the free-radical addition of a-bromo esters to 1-olefins. 

According to Holmbecg, the pK of the solution is the oidy factor which can determine the nature of the Optical antipode of a hydroxy acid fonned from a halo acid, Crnitrary to vdiat Waldmi hod suggested, the oinly effect of silver oxide would be to facilitate tin-formation of the /S-lactooe, -For example, the hydrolysis d... 

Type of reaction C-F and C-halo bond formation Reaction conditions Dichloromethane, room temperature Synthetic strategy One-step halofluorination of alkenes Catalyst Trihaloisocyanuric acid (TXCA) / HF-pyridine... 

Amines or ammonia replace activated halogens on the ting, but competing pyridyne [7129-66-0] (46) formation is observed for attack at 3- and 4-halo substituents, eg, in 3-bromopyridine [626-55-1] (39). The most acidic hydrogen in 3-halopyridines (except 3-fluoropyridine) has been shown to be the one in the 4-position. Hence, the 3,4-pyridyne is usually postulated to be an intermediate instead of a 2,3-pyridyne. Product distribution (40% (33) and 20% (34)) tends to support the 3,4-pyridyne also. 

Amino Acids. The formation of A/-halo-a-amino acids involves halogenation of the acid anion (13). /V-Cb1oro-CX-amino acids decompose to aldehydes and nitriles, the selectivity depending on pH and stoichiometry (110). For example, AJ-chloroalanine decomposes in the 6.5—10 pH range. 

KRdHNKE - ORTOLEVA PyndiniumSalts Formation oi kelo pyndinium salts by reaction of alpha halo katona darrvatives with pyndine and th cleavage to caiboxytic acids... 

Formation of oxiranes on the sterically more hindered side of the steroid ring system is usually carried out via /raw -halohydrins which afford oxiranes on treatment with base (c -Halohydrins yield ketones on exposure to base). Two general methods are available for the synthesis of tm s-halohydrins (1) the reduction of a-halo ketones and (2) the addition of a hypohalous acid to unsaturated steroids. 

Yet another example of an electrophilic addition is the reaction of alkenes with the hypohalous acids HO—Cl or HO-Br to yield 1,2-halo alcohols, called halohydrins. Halohydrin formation doesn t take place by direct reaction of an alkene with HOBr or HOC1, however. Rather, the addition is done indirectly by reaction of the alkene with either Br2 or Cl2 in the presence of water. 

A number of approaches have been tried for modified halo-de-diazoniations using l-aryl-3,3-dialkyltriazenes, which form diazonium ions in an acid-catalyzed hydrolysis (see Sec. 13.4). Treatment of such triazenes with trimethylsilyl halides in acetonitrile at 60 °C resulted in the rapid evolution of nitrogen and in the formation of aryl halides (Ku and Barrio, 1981) without an electron transfer reagent or another catalyst. Yields with silyl bromide and with silyl iodide were 60-95%. The authors explain the reaction as shown in (Scheme 10-30). The formation of the intermediate is indicated by higher yields if electron-withdrawing substituents (X = CN, COCH3) are present. In the opinion of the present author, it is likely that the dissociation of this intermediate is not a concerted reaction, but that the dissociation of the A-aryl bond to form an aryl cation is followed by the addition of the halide. The reaction is therefore mechanistically not related to the homolytic halo-de-diazoniations. 

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