Formyl derivative

Making a formyl derivative adds only 28 to the molecular weight of a compound, and for this reason has found particular favour in situations where several groups have to be blocked, such as in steroid chemistry, where the formyl derivatives appeared to be among the most suitable for the analysis of steroids by gas chromatography. However, it must be said that formyl derivatives are not necessarily the most volatile some of the per-fluoroacyl or methoxycarbonyl derivatives may be more volatile than the corresponding formyl ones. 

Edwards, Makin and Barratt found that acylation of steroids with 98-100% formic acid could result in artefacts, and adjusted the strength of the acid to 95% by adding water. Although a limit of 30 °C is usually recommended for formylation of steroids, they formy-lated at 40 °C for 30 minutes and still had average yields of 95% [43]. Alternatively, the 98-100% formic acid can be used at 50 °C for 10 minutes [44] or in the vapour phase at 80 °C in one hour with no appreciable destruction of any steroid [45]. 

Amines, either as salts or the free bases, can be formy-lated using sodium formate the base (or its salt, 1-5 mg) is treated with 98-100% formic acid (20 fxl), anhydrous sodium formate (10 mg) and acetic anhydride (200 rl) at 25 °C for 30 minutes in a reaction vial sealed with a cap containing a PTFE liner. Excess reagents are removed 

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Formyl derivatives. Formic acid condenses with primary and secondary amines to yield formyl derivatives ... 

Benzene- sulphon- amlde /)-Tolu- enesul- phon- amlde Benzal Derivative Plcrate 3-Nltro- phthal- Imlde 2 4- Dinitro- phenyl Derivative Formyl Derivative Phenyl thio- urea... 

Bento amide Benzene- sulphon- amide p-Tolu- enesul- phon- amide Plcrate Formyl Derivative Other Derivatives... 

Other carbonyl compounds are within the scope of the reaction ketones give amides, and aldehydes yield nitriles and formyl derivatives of amines ... 

The Leuckart reaction was originally conceived using a chemical called ammonium formate (HCOONH4) which is very similar to formamide (HCONH2) [30]. It is pretty much believed that this molecule donates its ammonium part to the P2P and then the formate part turns into formic acid (HCOOH) which then acts to reduce the intermediate into its stable formyl derivative (don t ask). 

Hydroxy-4-methylthiazole failed to react when submitted to Friedel-Crafts benzoylation conditions (349) on the other hand, it reacted normally in Gattermann and in Reimer-Tiemann formylation reactions, affording the 5-formyl derivative (348). 4-Methylthiazole is insufficiently activated and fails to react under the same conditions. 2,4-Dimethylthiazole undergoes perfluoroalkylation when heated at 200° for 8 hr in a sealed tube with perfluoropropyl iodide and sodium acetate (116) (358). 

The alkyl derivatives of thiazoles can be catalytically oxidized in the vapor phase at 250 to 400°C to afford the corresponding formyl derivatives (21). Molybdenum oxide, V2O5, and tin vanadate are used as catalysts either alone or with a support. The resulting carbonyl compounds can be selectively oxidized to the acids. 

Hydroformylation. Esters of maleate and fumarate are treated with carbon monoxide and hydrogen in the presence of appropriate catalysts to give formyl derivatives. Dimethyl fumarate [624-49-7] is hydroformylated in 1 1 CO/H2 at 100°C and 11.6 MPa pressure with a cobalt [7440-48-4] catalyst to give an 83% yield of dimethyl formylsuccinate [58026-12-3] product (72). 

Isomer separation beyond physical fractional crystallization has been accompHshed by derivatization using methyl formate to make /V-formyl derivatives and acetic anhydride to prepare the corresponding acetamides (1). Alkaline hydrolysis regenerates the analytically pure amine configurational isomers. 

Miscellaneous Reactions. The Reimer-Tiemaim reaction of sahcyhc acid (1) with chloroform and alkah (eq. 1) results in the 3- and 5-formyl derivatives. If the reaction is carried out with carbon tetrachloride, the corresponding dicarboxyhc acids form (eq. 2). The products (2) and (3) are 2-hydroxy-l,3-ben2enedicarboxyhc acid [606-19-2] and 4-hydroxy-l,3-ben2enedicarboxyhc acid [636-46-4] respectively. 

Amines react with CO in the presence of metal carbonyls forming /V-formyl derivatives or substituted ureas (152,153). 

Dimethylisoxazol-5-amine is easily acylated to its formyl derivative (697) which, on catalytic hydrogenation, undergoes ring cleavage and recyclization to yield 5,6-dimethyl-pyrimidin-4(3H)-one (698) other acyl derivatives give analogous 2-substituted pyrimidines... 

HCO2H, DCC, Pyr, 0°, 4 h, 87-90% yield. These conditions produce N-formyl derivatives of r-butyl amino acid esters with a minimum of race-mization. -... 

On digestion of this solid mass with 1 1. of ice and water, the sodium salt of the enol dissolves in the water, and the unreacted ester is removed by extracting the aqueous layer with two 200-ml. portions of ether (Note 5). The foimyl derivative settles out as an oil upon acidification of the aqueous layer with dilute sulfuric acid. The oil is extracted with three 200-ml. portions of ether, and the ethereal extract is washed several times with water and dried over anhydrous sodium sulfate. The ether is distilled, and, to remove traces of ethyl formate, the oil is heated on a steam bath under a pressure of 20-30 mm. for 1 hour. The remaining yellow formyl derivative weighs 27-29 g. (Note 6). 

A convenient synthesis of A -3-ketones in the 5 5 series uses DDQ in one step. This introduction has to be done indirectly because of the unfavorable direction of enolization. In this scheme, advantage is taken of the equilibrated formylation at C-2 of 5i5-3-ketones. Dehydrogenation of the 2-formyl derivative (72) proceeds rapidly with DDQ and deformylation is achieved in the presence of a homogeneous catalyst. A related approach involves preparation of the 2i -bromo-5i5-3-ketone by bromination of the 2-formyl compound (72). ... 

In 1927 Putochin studied the effect of temperature on the nature of the products formed when the formylation reaction was carried out in benzene and observed that 1-formyl derivatives were the major products obtained at low temperatures, whereas the 3-formyl derivatives predominated at higher temperatures. Britton et al. in 1947 claimed that the formation of the 3 -formylindole derivative is probably favored, relative to the alternate 1-formylation process, by elevated temperatures and pressures.However, it was apparently not possible to suppress completely the formation of the 1-formyl derivatives and yields of the order of 40% of both products were usually obtained. 

JHC787), N,A -diethylcarbamoyl chloride the amide 170 (95T10969), and, contrary to earlier reports, DMF gives the 7-formyl derivative 171 (95JHC787). 

Oxidation of 9-(4-pyridylvinyl)-7-methyl-2-morphohno-4//-pyrido[l, 2-a -pyrimidin-4-one with cetyltrimethylammonium permanganate in CH2CI2 at room temperature for 5 h yielded a 9-formyl derivative (01MIP9). 

Vilsmeier-Haack formylation of 2-(4-methyl-l-piperazinyl)-4//-pyrido-[l,2-n]pyrimidin-4-one with a mixture of POCI3 and DMF at 95°C gave a 3-formyl derivative (93FES1225) while ethyl 4-oxo-6,7,8, 9-tetrahydro-4//-pyrido[l,2-n]pyrimidine-2-acetate at 50 °C yielded a 9-dimethylaminomethylene-3-formyl derivative (01MI4). 3-Formyl-2-hydroxy-8-[2-(4-isopropyl-l,3-thiazol-2-yl)-l-ethenyl]-4//-pyrido[l,2-n]pyri-midin-4-one was obtained from the 3-unsubstituted derivative with oxalyl chloride-DMF reagent in CH2CI2 at room temperature for 3h (OlMIPl). 

Reaction of 2-(A -alkyl-A -benzylamino)- and 2-[A -(rraM-crotyl)-A -ben-zylamino]-3-formyl-4/7-pyrido[l,2-n]pyrimidin-4-ones (260, R = H, Me) with tosylamine gave compounds 268 via compounds 266 and 267 (96T13097). The results of kinetic studies and MP3 calculations on the 3-formyl derivatives 252, 260 and the imines 262, 263 suggested a concerted nature for azepine-ring formation. 

Formyl derivative 360 was prepared by oxidation of 7-ethenyl derivative 359 with OSO4 in the presence of NaI04 (98MIP7). 

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