Dimethylformamide aldehyde synthesis

Aldehyde synthesis [before references], Franzen5 gives a procedure for drying trimethylamine oxide dihydrate (supplied by Beacon Chemicals) by mixing with dimethylformamide and distillation, eventually in vacuum, until the solvent is all removed. A solution of the residue in chloroform is treated with n-octyl iodide, added dropwise with stirring in 20-30 min. After refluxing for 20 min., the solution is cooled and treated with 2 N aqueous sulfuric acid at 50°. The chloroform layer is... 

C ( propyl) N phenylmtrone to N phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami noacetone hydiochlonde, 46,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47, 1 /3-chloro a,0 unsaturated, from ke tones and dimethylformamide-phosphorus oxy chloride, 46, 20 from alky 1 halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodumide, and pyndimum tnfluoroacetate, 47, 27 Alkylation, of 2 carbomethoxycyclo pentanone with benzyl chloride 45,7... 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

The strategies used in the synthesis of polymethine dyes are illustrated for a series of indoline derivatives in Scheme 6.1. There is an even wider range of synthetic routes to polymethine dyes than is described here, but they are based for the most part on a similar set of principles. The starting material for the synthesis of this group of polymethine dyes is invariably 2-methylene-1,3,3-trimethylindolenine (121), known universally as Fischer s base. As illustrated in the scheme, compound 121 may be converted by formylation using phosphoryl chloride and dimethylformamide into compound 122, referred to as Fischer s aldehyde, which is also a useful starting material for this series of polymethine dyes. When compound 121 (2 mol) is heated with triethylorthoformate (1 mol) in the presence of a base such as pyridine, the symmetrical cyanine dye, C. I. Basic Red 12 109 is formed. The synthesis of some hemicyanines may be achieved by... 

A further example of electrophilic substitution is the synthesis of pyrazole aldehydes by formylation with dimethylformamide.620,628... 

There are several methods for the direct introduction of an aldehyde group into an aromatic compound. In the Vilsmeier-Haack reaction, activated aromatic systems such as aryl ethers and dialkylanilines are formylated by a mixture of dimethylformamide, HCONMe2, and phosphorus oxychloride, POCL, (Scheme 6.4). The process involves elec-trophilic attack by a chloroiminium ion, Me2N=CHCl, formed by interaction of dimethylformamide and phosphorus oxychloride. Hydrolysis of the dimethyl imine completes the synthesis. 

Owing to their positive charge, 1,2-dithiolium cations are, of course, almost unreactive to electrophiles. On the other hand, their conjugate bases, such as 3-alkylidene-l,2-dithioles, react easily with electrophilic reagents such as aromatic aldehydes, dimethylformamide, and nitrous acid. Some of these reactions are useful for the synthesis of partially bonded compounds and have been described, for papers prior to 1970, in a previous review (Ref 2 pp. 181, 187, 193). 

A more versatile synthesis of the pteridine ring from pyrimidine-4,5-diamine involves the initial formation of a Schiff base by reaction with an aldehyde followed by cyclization with triethyl orthoformate or dimethylformamide diethyl acetal. The general reaction is shown below, and is exemplified by the synthesis of 6-phenylpteridine-2,4(1 //,3//)-dione (2)." 7... 

An alternative approach to the synthesis of benzodiazepines involves the reaction of /3-chlorovinyl carbonyl compounds with o-phenylenedi-amine. In the first example methyl /3-chlorovinyl ketone was used to obtain 5-methylbenzodiazepinium chloride.31 An extensive investigation has been made of the use of /3-chlorovinylaldehydes for the preparation of 2,3-substituted benzodiazepines.3233 The preferred conditions for reaction were in alcoholic hydrogen chloride. By this means a variety of 2-aryl-, 2,3-cycloalkeno-, and 2,3-diarylbenzodiazepines was prepared. If no acid is present an uncyclized anil results, formed by condensation of one amino group with the aldehyde. Since the /3-chlorovinylaldehydes are themselves readily obtained by reaction of a-methylene ketones with phosphoryl chloride and N, JV-dimethylformamide or jV-methylformani-lide,34 this provides an attractive route to 2,3-disubstituted benzodiazepines. 

The silylated methyl ester was then a-methylated with lithium diisopropylamide and methyl iodide in tetrahydrofuran. Reduction of methyl 10-( erl-butyldimethylsilyloxy)-2-methyldecanoate with DIBAL in ether at -78°C afforded the corresponding aldehyde. The 10- tert-butyldimethylsilyloxy)-2-methyldecanal was subsequently coupled in a Wittig reaction with 1-hexyltriphenylphosphonium bromide and n-butyllithium affording (Z)- and ( )-1 -(teri-butyldimethylsilyloxy)-9-methyl-10-hexadecene in a 9 1 ratio, respectively. Deprotection with tetrabutylammonium fluroride (TBAF) in tetrahydrofuran and final oxidation with pyridinium dichromate (PDC) in dimethylformamide resulted in a 9 1 mixture of (Z)- and ( )-9-methyl-10-hexadecenoic acid as shown in Fig. (7). As was also the case with acid 6, the stereochemistry at C-9 in 7 is not known. The key step in the synthesis of the allylic methyl group was a-methylation of a methyl ester, followed by reduction to the corresponding aldehyde, which was used in the subsequent Wittig reaction. 

Dimethoxybenzaldehyde has been employed in the synthesis of deazaflavins (pyrimidoquinolines). Thus, 6-butylamino-3-methyluracil with the aldehyde in dimethylformamide suspension after being heated for 4 hours afforded in 70% yield, 10-butyl-9-methoxy-3-methyl-5-deazaflavin (ref.90). 

The structure of this aldehyde was proved by H. Quiniou through an independent synthesis—formylation of the diaryltrithiapentalene by dimethylformamide and phosphorus oxychloride (see Section... 

A new synthesis of racemic oleuropeic acid (216) starts with the known Diels-Alder reaction between methyl vinyl ketone and chloroprene, yielding the chloro-ketone (217). The acid function is introduced by exchanging the chlorine atom for lithium, followed by conversion into the aldehyde with dimethylformamide, and the additional methyl group is put in with a Grignard reaction (Scheme 16). ... 

Aryloxazole-4-aldehydes 59 (R = H, Me, Cl, Br or Ph) are formed in good yields in the reaction of 2-azidoacetophenones 58 with the Vilsmeier reagent dimethylformamide-phosphorus oxychloride <97TL6089>. A one-pot synthesis of the cyanooxazoleamines 60 is by the action of dicyclohexylcarbodiimide and pyridine on mixtures of aminonalononitrile tosylate and carboxylic acids <97S861>. 

Metallation of thieno[2,3-Z ]thiophene (142) followed by the reactions of the resulting mono- and dilithium derivatives with dimethylformamide afforded aldehydes 173 and 174, which served as the starting compounds in the synthesis of heterohelicenes 175a, b and 176a, b (73JA3692). 

Vilsmeier-Haack Formylation with N,N-Dimethylformamide. In the presence of phosphorus oxychloride (POCI3), the—CHO group of N,N-dimethylformamide can be attached to the pyrrole ring (Scheme 7.7). This is a highly useful process for the synthesis of pyrrole aldehydes, which are precursors of pyrrole acids by oxidation, of pyrryl carbinols by reductions with LiAHtj, and of other products (Scheme 7.7). 

Catalytic amounts of camphor-10-sulfonic acid (CSA) in methanol and dichloro-methane smoothly cleave the orthoester function in 23, giving the intermediate y-lactone-l,3-diol. Subsequent protection of the primary alcohol function with di-methylphenylchlorosilane (TPSCl) in dimethylformamide with imidazole as the base and of the secondary alcohol function via alcoholate with benzylbromide (BnBr) following WiLLlAMSON s ether synthesis yields the y-lactone 24. Its reduction with lithiumaluminumhydride leads to two vicinal primary alcohol groups. Thereafter, camphor-10-sulfonic acid (CSA) in dichloromethane selectively cleaves the TBS ether and catalyzes the transketalization with acetone dimethyUcetal to the precursor 25 of the aldehyde 8. Smooth oxidation of the primary alcohol function in 25 is achieved with tetrapropylammoniumperruthenate (TPAP) and A-methyl-morpholine-A-oxide (NMO) in acetonitrile. 

---