From halo acids

Lactones can be prepared from halo acids by treatment with base (see 16-63). This has most often been accomplished with y and 5 lactones, but macrocyclic... 

Nucleophilic substitution by ammonia on a halo acids (Section 19 16) The a halo acids obtained by halogenation of car boxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reac tive substrates in nucleophilic substitu tion processes A standard method for the preparation of a ammo acids is dis placement of halide from a halo acids by nucleophilic substitution using excess aqueous ammonia... 

A process for the commercial synthesis of -phenylene diisocyanate using terephthalamide [3010-82-0] as a precursor and involving N-halo intermediates has been studied extensively (21). The synthesis of 1,4-diisocyanatocyclohexane from terephthaUc acid [100-21-0] also involves a nitrene intermediate (22). 

Participation of fluorocarbocations, derived from carboxylic acids and from halo acetones, in reactions of carbonyl compounds with sulfur tetrafluoride has been directly evidenced by trapping them with aromatic hydrocarbons [207, 20S],... 

The tosylatc must come from alcohol (44), Disconnection Lo an epoxide (45) is no good as the amine will attack the wrong atom. Change of oxidation level to (46) is more hopeful as the a-halo acid (47) is easily made. Another possibility is to use naturally occurring a 1 an ine ( 48),... 

Reineke W, W Otting, H-J Knackmuss (1978) cw-Dihydrodiols microbially produced from halo- and methylbenzoic acids. Tetrahedron 34 1707-1714. 

Af-Ethyl-A-(3-halo-2-methylphenyl)aminomethylenemalonates (106, R = Et, R1 = Me, R2 = Hlg, R3 = H) were heated in polyphosphoric acid, prepared from phosphoric acid and phosphorus pentoxide, at 140°C for 40 min. The reaction mixture was then poured into water, and the product was hydrolyzed with 10% aqueous sodium hydroxide to give quinoline-3-carboxylic acids (696, R = Et, R1 = Me,R2 = Hlg) in 68-70% yields (80GEP3007006). 

Although alcohols are oxidized by tetra-n-butylammonium persulphate when the reaction is conducted in dichloromethane, tetrahydropyranyl ethers have been produced (>90%) when attempts to oxidize the alcohol are conducted in tetrahydro-pyran (see Chapter 10) [ 19], Tetrahydrofuranyl ethers have been prepared by an analogous method [20,21 ]. Base-mediated elimination of halo acids from P-halo alcohols under phase-transfer catalysed conditions produce oxiranes in high yield (70-85%). The reaction has particular use in the synthesis of epihalohydrins from p,y-dihalo alcohols [22],... 

The biochemical reduction of a, -unsaturated -haloaliphatic acids by means of Clostridium kluyveri yielded halogen-free satmated acids. The same products were obtained from saturated -halo acids. However, the same microorganism converted ix, -unsaturated a-halo acids to saturated a-halo acids with R configuration. Yields of reduction of a-fluoro-, a-chloro- and a-bromocrotonic acid ranged from 30% to 100% [330]. 

Fig. 14 Tandem Ugi-Sjj2 starting from a-halo acids...

In contrast to thiomiinchnones, thioisomiinchnones (5) (l,3-thiazolium-4-olates) have received considerable attention over the past three decades, and a rich array of 1,3-dipolar cycloaddition chemistry is described in Section 10.2.5. These heterocycles were initially constructed by Potts (1,53,57) from thioamides and a-halo acid chlorides, an example of which is shown in Scheme 10.17 (58). 

Formation of Acyl Halides from Carboxylic Acids Halo-de-hydroxylation... 

From thiol acids and a-halo ketones Thiols... 

Mildly basic to neutral conditions for the ring closure of 1,3-halohydrins include tetra-phenylantimony methoxide as an effective non-basic reagent for oxetane synthesis from 1,3-bromohydrins (90S106). The salts of (3-halo acids cyclize in ionizing media to oxetan-2-ones, as do (3-diazonium carboxylates (64HC(l9-2)787). Thietanes are obtained analogously. 

One of the more important uses of thioureas has been in the preparation of 2-imino-4-thiazolidinones, first reported by Meyer135 and Andreasch,136 138 via reaction with a-halo acids or esters. This reaction has been covered by Brown139 in a review on 4-thiazolidinones which appeared in 19(51, and, therefore, will not be discussed in detail here. The corresponding reaction between a-halo acids or esters and scleno-ureas to produce 2-iminoselenazolidin-4-ones is also known and has been reviewed.77-78 Akerblom140 has attempted to clear up some of the confusion in the literature on whether 3-alkyl-2-iminothiazolidin-4-ones (63) or 2-alkylamino-2-thiazolin-4-ones (64) are formed from 1-alkyl-thioureas and chloroacetic acid. She found that the reaction in water... 

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. 

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