Fluorobenzaldehydes

Tetrasubstituted phosphonium halides are just as effective as their ammonium counterparts. A combination of tetraphenylphosphonium bromide and either 18-crown-6 or polyethylene glycol dimethyl ether with spray-dried potassium fluoride converts 4-chlorobenzaldehyde to 4-fluorobenzaldehyde in 74% yield [67] In addition, the halogen of a primary alkyl chloride or bromide is easily displaced by fluorine in aqueous saturated potassium fluoride and a catalytic amount of hexadecyltributylphosphonium bromide [68] (Table 7 Procedure 4, p 194)... 

Kirk and coworkers recently reported preparation of 6-flouro-meta-tyrosine 29 based on an Erlenmeyer-Plochl azlactone strategy from 2-benzyloxy-5-fluorobenzaldehyde. 

Condensation of m-fluorobenzaldehyde with malonic acid leads to the trans cinnamic acid 96 acylation of the acid chloride with cyclopropylaminc leads to amide 97 (cinflumide), a muscle relaxant [24]. 

Ferroglycine sulfate Ferrous fumarate Fluoranthene Flora ntyrone Fluoroacetyl chloride Afloqualone p-Fluorobenzaldehyde Sulindac Fluorobenzene Flubendazole o-Fluorobenzoyl chloride Flunitrazepam... 

Reactions between aldehydes and alkynes to give propargyl alcohols are also described in Kitazume and Kasai s paper [55]. Here, various aldehydes such as benzaldehyde or 4-fluorobenzaldehyde were treated with alkynes such as phenylethyne or pent-l-yne in three ionic liquids [EDBU][OTf], [BMIM][PFg], and [BMIM][BF4] (Scheme 5.1-27). A base (DBU) and Zn(OTf)2 were required for the reaction to be effective the yields were in the 50-70 % range. The best ionic liquid for this reaction depended on the individual reaction. 

CjjHjClFN 367-27-5) see Norfloxacin Pefloxacin 2-chloro-6-fluorobenzaldehyde (C7H4CIFO 387-45-1) see Flucloxacillin 2-chloro-6-lluorobenzaldehyde oxime (C7H5CIFNO 443-33-4) see Flucloxacillin... 

There were two potential starting materials for Trost s Mo chemistry (Scheme 2.7). The first approach utilized the commercially available 3-fluorocinnamic acid (4). However, reduction of 4 did not proceed well with various reducing agents and provided the desired allylic alcohol 28 in only mediocre yield. Alternatively, 3-fluorobenzaldehyde (29) was used as the starting material. Vinyl Grignard addi-... 

Ni11 complexes of thiosemicarbazones derived from p-fluorobenzaldehyde and differently substituted thiosemicarbazides (434, 435) are square planar [NiL2] species with the S and hydrizine-N atoms in tram position to each other and a slight tetrahedral distortion in some cases.1235,1236... 

Triisopropyl-1,3,5-dioxaphosphorinane (26) and its sulfide react with chloral, p-fluorobenzaldehyde, and acetaldehyde [Eq. (18)]. In the latter case, the hydroxymethyl derivative (29) (R = Me) was obtained. The reaction with chloral and p-fluorobenzaldehyde does not stop at the addition stage, but proceeds further to form the oxides (30) (R = CCI3,p-F-C6H4) (81IZV2776). 

Hydantoin (5.2 g, 52 mmol) was added to piperidine (9.9 mL, 100 mmol) in a twonecked reaction flask equipped with a magnetic stirrer bar and heated to 130 °C under nitrogen flux. 4-Fluorobenzaldehyde (5 mL, 47 mmol) was added dropwise to the stirring mixture. The reaction was monitored by TLC (eluent ethyl acetate/cyclohex-ane, 1 4) and reached completion in 30 min. 

Dondoni pioneered the use of 2-(trimethylsilyl)thiazole (71) as a formyl anion equivalent for the homologation of aldehydes. Extension of this reaction to ketones would be very useful, but has thus far been restricted to tritluoromethyl cases. However, it has now been widened to include several a, a -alkoxy ketones, as demonstrated in a new route to branched-chain monosaccharides. Aldehydes catalyse the reaction, although the scope is still limited electrophilic aldehydes, such as 2-fluorobenzaldehyde, promote the addition of (71) to electrophilic ketones. 

Oxidations of [ F]Fluorobenzaldehydes to [ F]Fluorophenols. . 228 Decarbonylation of F-Aromatic Aldehydes and AppHcations. . 229... 

Both [2- F] and [4- F]fluorobenzaldehydes are key intermediates in the synthesis of N-[ F]fluorobenzylamines via reductive aminations. This methodo o-gy has been successfully appHed to the preparation of a potential ace y -cholinesterase inhibitor [143] and of fluoro analogues of dexetimide, potent ligand of muscarinic cholinergic receptor [144] (Scheme 23). 

F]Fluorobenzaldehydes have also been used as starting materials for the preparation of enantiomers of [6- F]fluoronorepinephrine,a myocardial marker [166]. The key step is the formation of a protected F-cyanhydrine which is reduced into an amino alcohol. Deprotection, purification and resolution on a chiral column provide both enantiomers (Scheme 30). 

In order to decrease the number of chemical steps in the synthesis of l-[4- F]fluorophenylalanine, a potential marker for probing protein synthesis [140a], [4- F]fluorobenzaldehyde has been directly condensed with an imino-lactone. Hydrolysis then chiral HPLC yield the S amino acid in 5 % radiochemical yield (Scheme 33). 

Direct condensation of 4, 5-dimethoxy-[2- F]fluorobenzaldehyde with an asymmetric chiral inductor [170] followed by L-selectride reduction of the olefinic double bond and hydrolysis leads to [6- F]fluoro-L-DOPA in 3 % radiochemical yield and an ee higher than 90% (total synthesis time 125 min) (Scheme 34). This method avoids the preparation of F-fluorobenzylhalides. 

Transformation of [4- F]fluorobenzaldehydes into [4- F]fluorophenyl-alkenes using the Wittig reaction has been relatively unexplored. Examples are shown in Scheme 35. It requires the in situ generation of the ylid [171] by reaction of the phosphonium bromide with propylenoxide [172]. These conditions, successfully used in carbon-11 chemistry [173], have however the drawback of leading to a mixture of Z and E stereoisomers. 

For example, p-[ F]fluorobenzaldehyde (A) is easily obtained in moderate to high yields from the corresponding nitro- [174-176] or trimethylammonium triflate precursor (PI) [167,168] using K[ F]F-K222 in DMSO at 120 °C for 10 min. 

Multi-step syntheses of a radiopharmaceutical involving an aromatic nucleophilic radiofluorination An example of a multi-step radiosynthetic pathway is the no-carrier-added synthesis of 6-[ F]fluoro-L-DOPA (Scheme 45). The first step involves the preparation of 4,5-dimethoxy-2-[ F]fluorobenzaldehyde from the corresponding nitro-substituted benzaldehyde. The following steps involve its condensation with an asymmetric chiral inductor [206] followed by L-selectride reduction of the... 

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