3.5- dichlorobenzoyl chloride

CH3SCH20)(CH2)3C02H, 2,6-dichlorobenzoyl chloride, Pyr, CH3CN, 70% yield. The MTMB group was selectively introduced onto the 5 -OH of thymidine. 

Reaction of 2,3-dichlorobenzoyl chloride with cyanide ion leads to the corresponding benzoyl cyanide (141). Condensation of that reactive intermediate with aminoguanidine 142 leads to the hydrazone-like product 143. Treatment with base results in addition of one of the guanidine amino groups to the nitrile function and formation of the 1,2,4-triazine ring. The product, lamo-trigine (144), is described as an anticonvulsant agent [31]. 

FIGURE 5.21 Methods for anchoring an Fmoc-amino acid to the hydroxymethyl group of a linker-resin. (A) 4-Dimethylaminopyridine-catalyzed acylation by the symmetrical anhydride.19 (B) Acylation by a mixed anhydride obtained from 2,6-dichlorobenzoyl chloride.39 (C) Acylation by the acid fluoride.50 (D) Dicyclohexylcarbodiimide-mediated acylation in the presence of 1-hydroxybenzotriazole.52... 

The facile homogeneous catalysed reduction of acid chlorides to alcohols has many advantages over reduction with sodium borohydride in hydroxylic solvents where rapid reaction of the acid chloride with the solvent can occur [10]. The procedure has been incorporated into a simple one-pot conversion of aroyl chlorides into the corresponding benzyl chlorides (Scheme 11.1) under liquidrliquid or solid-liquid two-phase conditions [11], The reduction of a limited number of aryl compounds was reported with ca. 70% overall yields, although poorer yields result from the reduction of 4-nitro-, 2-cyano- and 2,4-dichlorobenzoyl chlorides, and the reduction failed completely with terphthaloyl chloride and with its 2,3,5,6-tetrafluoro derivative [11]. 

A catalytic amount of tetraphenylphosphonium bromide is required for the preparation of 3,4-difluorobenzoyl fluoride (11) from 3,4-dichlorobenzoyl chloride (9) with potassium fluoride.32 While 11 is formed only in 23% yield, the partially fluorine substituted intermediate 10 can be treated again with potassi um fluoride and tetraphenylphosphonium bromide at 230 °C for 10 h. In this way besides the chlorine atom of the acid chloride in 9 both the aromatic chlorine atoms are also displaced.32... 

Molinate (27) (65USP3198786) is simply made from perhydroazepine and 5-ethyl chlorothioformate, while the recently introduced pyrazolate (28) (75GEP2513750) is synthesized from l,3-dimethylpyrazol-5-one, itself easily made from methylhydrazine and ethyl acetoacetate. Reaction of the pyrazolone with 2,4-dichlorobenzoyl chloride takes place on carbon at the 4-position, and then treatment with toluene-p-sulfonyl chloride gives pyrazolate. Difenzoquat (29) (75USP3922161) is readily available from 3,5-diphenylpyrazole by methylation. Ethofumesate (30) (69GEP1926139) is synthesized from p-benzoquinone (Scheme 8). 

In fact, when 4-nitrobenzoyl chloride was used to achieve 4-nitrobenzoylthiosemicarbazide, a cyclic product was obtained with high yields. Based on analytical and spectral data, the obtained product was 1,3,4,5-oxathiadiazepine 55 and not the expected carbazide. A similar behavior was observed when 2,4-dichlorobenzoyl chloride was reacted, though with some difference. In this case, a mixture of two products was obtained, which after purification were identified as 1,3,4,5-oxathiadiazepine 56 and the desired 2,4-dichlorobenzoylthiosemicarbazide (Equation 9) <2004FA945>. 

Anhydrous AICI3 (219 g, 1.64 moles) was added in portions over a 35 to 40 min period to a stirred solution of 3,4-dichlorobenzoyl chloride (313.5 g, 1.50 moles) in benzene (1.125 L) and dichloromethane (75 ml), with the mixture maintained at 3° to 5°C during the addition period. The reaction mixture was held at 0° to 5°C for another hour and then poured into 2.5 L of ice/water and stirred until the complex had decomposed. The organic and aqueous layers were then separated and the organic layer combined with one ethyl acetate... 

Thus, as shown in Scheme 19, treatment of the hydroxy acid 59 with the commercially available 2,6-dichlorobenzoyl chloride, triethylamine, and DMAP in toluene at 100 °C gave the cyclized product 60 in 67% yield. 

Mixed anhydrides produced from the commercially available 2,6-dichlorobenzoyl chloride (5, see Table 1) and Fmoc-protected amino acids have proven to be convenient reagents for acylating Wang-type resins.P Reaction takes place with good yields and nninimal racennization, except for the case of Fmoc-Cys(Trt)-OH (4% D-isomer) and Fmoc-His(Trt)-OH (27% D-isomer). In the latter case, the use of Trt-His(Trt)-OH (<1.0% d-isomer) circumvents the problem. 

Acylation of Hydroxymethyl Resins Using 2,6-Dichlorobenzoyl Chloride General Proceduret ... 

The hydroxymethyl resin and the Fmoc-protected amino acid (2 equiv) were shaken in DMF (5 mL - g resin) for 15 min at 25 °C. Pyridine (3.3 equiv) and 2,6-dichlorobenzoyl chloride (5 2 equiv) were successively added and the suspension was shaken for 15-20 h. After washing, any remaining hydroxy groups were capped as described in Section 4.3.1.3.1.1,... 

Scheme 12.8 Synthesis of ferrocene amino acid according to Heinze (i) f-BuLi, -70°C (ii) quenching with iodine (iii) reaction in pyridine with phthalimide and Cu20 as catalyst (iv) hydrazinolysis in ethanol (v) A-acetylation with Ac20 (vi) selective Friedel-Crafts acylation with 2,6-dichlorobenzoyl chloride at the unsubstituted Cp ring (vii) base hydrolysis (viii) removal of the acetyl protection group with hydrochloric acid.

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