Vilsmeier-type salts

Chlorination of Amides and Ureas. Vilsmeier-Type Salts... 

A second method that we considered involved condensation of a carbohydrate-derived phosphate salt with an in situ-generated phosphoryl dichloride.21 The requisite phosphoryl dichlorides are prepared via exposure of a lipid phosphate to a Vilsmeier-type reagent. This protocol has been used successfully for the preparation of lipid diphosphate linkages in the dolichol series (i.e., lipids lacking an allylic double bond proximal to the diphosphate linkage). However, we were once again, hesitant to expose our undecaprenyl phosphate precursor to activation conditions that produce HC1 as a by-product. 

Vilsmeier-type reagent 749 reacted with imines 750 to afford enaminoimine hydrochlorides 751, which were transformed to pyrazoles 752 upon addition of hydrazine (Scheme 94) <2000JHC1309>. A variety of vinylogous iminium salts 753 were useful precursors for the regiocontrolled synthesis of heterocyclic appended pyrazoles 754 (Equation 161) <2002T5467>. 

In many cases synthesis of the fluorinated 1,3-CCC-bielectrophile precursors is the most difficult part of the syuthetic sequeuce and using classical methods is usually accomplished by the use of highly toxic fluoroacetic add derivatives in Claisen condensation with ethyl formiate [81], ethyl chloroformate [95,96], diethy-loxalate [82, 97], acetyl, benzoyl chlorides [82] or Vilsmeier-type formylation [98, 99] (Scheme 13). The product of Vilsmeier-type formylation is 3-dimethylamino-2-fluoroacrolein 54 which reacts with triethyloxonium tetrafluoroborate and dimeth-ylamine to give the vinamidinium salt 55 [91], which also can be used as 1,3-bielectrophile (see Scheme 19). Also Reformatsky-type synthesis of ethyl a-fluoroacetoacetate 52 starting from ethyl chlorofluoroacetate 56 was described in 20 % yield [82]. 

Another characteristic of electrophilic reactions of pseudoazulenes is the application of numerous cations as the electrophile, for example, diazonium salts and Vilsmeier- Haack s reagent (see Table VI), tropylium ion,135 triphenylmethyl cation,"4 pyrylium ion,119 and dithiolium ion.166 Very stable cations are formed (e.g., 120) addition of base releases the substituted pseudoazulene (see example in Eq. 10). Generally reactions of this type are thermodynamically favored (see also Section IV,B). The site of substitution... 

Vilsmeier-Haack diformylation of 2-methylene-l,3-diselenole 140 gave 2-diformylmethylene-l,3-diselenole 141 (Equation 20) that served as a precursor for the dendralene-type vinylogs of tetrathiafulvalene 1, 2, 39, 142, and 143 by condensation with suitable dithiolium phosphonium salts or phosphonates in the presence of base <2001JOC7757>. 

A type Had cyclization of vinamidinium salt 24 with a-aminoacetophenone 25 in the presence of sodium hydride led to the formation of 2-keto-4-arylpyrrole 26 <05T1845>. The latter was utilized in a regiocontroUed preparation of the polycitone alkaloids. Vinamidinium salt 24 was readily available from phenylacetic acid 23 by a Vilsmeier-Haack type process. 

Chlorocarbenium salts (Vilsmeier-Arnold type) are reported to react with silylated cyanurate... 

The benzocyclobutene-dihydroisoquinoline condensation shown in Scheme 12 gave the quaternary protoberberine salt (124 R = H), the intermediate dihydroderivative of this evidently losing hydrogen under the reaction conditions. " This type of salt [e.g. (124, R = OMe)] and its dehydro-analogue can be obtained by Vilsmeier-Haack reactions of 1-benzyl-3,4-dihydroisoquinolines and 1-... 

Vilsmeier-Haack formylation of 2,5-diaryl-6a-thiathiophthens leads to the 3-formyl compounds, which are also obtainable from 3-aryl-l,2-dithiolium salts by treatment with triethylamine, and details have been given for the bromination of 2,5-disubstituted thiathiophthens. Nitration of 2-methylthio-5-phenyl-6a-thiathiophthen gives the 3-nitro-compound in poor yield, and attempted nitrosation experiments lead, in several examples, to rearranged structures of type (19), although the first stage of these reactions is presumed to be electrophilic attack on the 3-position. 

From Vllsmeier Salts (Type Q.—The Vilsmeier-Haak reaction has been applied to the synthesis of 2- (or 5-)substituted 4-cyanoisothiazoles (45). Thus, condensation of a Vilsmeier salt prepared from phosphorus oxy-... 

Dithiolylidene derivatives of malonic acid (26) decarboxylate in perchloric acid-acetic acid to give 5-ary 1-1,2-dithiolium perchlorates. Vilsmeier salts of type (27) are produced by condensation of 5-methyl-1,2-dithiolium salts with dimethylthioformamide, and a similar trans-structure (28) is formed when 6-methyl-l,6a-dithia-6-azapentalene (see Chapter9) is protonated. 

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