Recherches sur la formation et la transformation des esters LXXVI [1] Sur la réaction de l'isocyanate d'o-méthoxycarbonyl-phényle avec quelques acides amino (ou hydrazino) alcoyl-orthophosphoriques et -sulfuriques

o-Methoxycarbonyl-phenyl isocyanate reacts with mono-aminoalkyl orthophosphoric and sulfuric acids to yield the corresponding 1,2,3,4-tetrahydroquinazoline-2,4-dione-3-ethyl phosphoric (or sulfuric) monoesters which are isolated as sodium salts. 1,2,3,4-Tetrahydroquinazoline-2,4-dione-3-ethyl phosphoric acid has been isolated by adding hydrochloric acid to an aquous solution of its sodium salt.     

Recherches sur la formation et la transformation des esters LXXVIII. Sur la réaction de l'isothiocyanate d'o-méthoxycarbonyl-phényle avec des diamines et l'hydrazine,et sur la cyclisation de quelques N-phényl-N′-hydroxyalcoyl-thio-urées

1-Amino-2-dimethylamino-ethane and 1-amino-3-dimethylamino-propane react with o-methoxycarbonylphenyl isothiocyanate (I) to yield the corresponding 3-(ω-dimethylaminoalkyl)-2-thiono-1,2,3,4-tetrahydroquinazolin-4-ones (V). The tertiary amino group of V is quaternized to the corresponding ammonio derivative VI when treated with methyl iodide in methanol.     

Recherches sur la formation et la transformation des esters LXXIX [1]. Sur la réaction de l′isothiocyanate d′o-méthoxycarbonyl-phényle avec divers acides et l′acide sérinephosphorique

Amino acids devoid of «leaving groups» on their β carbon atom (neither ? OH: serine, nor ? SH: cysteine) react with o-methoxycarbonyl-phenyl isothiocyanate (I) in the presence of one equivalent of NaOH, in water-dioxane or in ethanol, to yield the corresponding hydroquinazolinone derivatives II which were isolated as free acids. When treated with CH₃COOH + conc. HCl the hydroquinazolinone resulting from the reaction of L -serine with I undergoes a nucleophilic attack of the carbon bearing the leaving group ? OH by a lone pair of electrons of S; this attack produces the formation of an additional thiazolidine ring, yielding the thiazoloquinazolinone derivative (?)-III. In an analogous reaction DL -serine phosphoric acid treated with I at pH 8–9 yields the corresponding substituted hydroquinazolinone which, boiled in 1N hydrochloric acid, undergoes ring closure to (±)-III by the same mechanism as the serine derivative (leaving group: ? OPO₃H₂). L -Cysteine reacted with 2 equiv. of I and then treated with CH₃COOH + conc. HCl gives two products: (?)-III produced by the same mechanism as for serine (leaving group: ? SH), and the quinazolinone derivative IV where the ? SH group is also thiocarbamoylated.     

Recherches sur la formation et la transformation des esters LXXV[1]. Amines,amino-alcools et aminoalcoyl-monoesters des acides orthophosphorique et sulfurique: thiocarbamylation par l'isothiocyanate d'o-méthoxycarbonylphényle sans ou avec cyclisation intramoléculaire

o-Methoxycarbonyl-phenylisothiocyanate V and primary alkylamines (R″? NH₂) reacted in the appropriate medium yield the corresponding 2-mercapto-3-alkyl-3, 4-dihydro-quinazolinone-4 derivatives VI (the ? NH₂ group is thiocarbamoylated by the ? N?C?S group and then acylated in an intramolecular reaction by the ? COOCH₃ group with elimination of CH₃OH).     

Recherches sur la formation et la transformation des esters LXXI Sur la préparation des acides ω-(phénylthiocarbamylamino)-alcoylphosphoriques et sur leur scission à divers pH

Sodium ω-phenylthiocarbamylaminoalkyl phosphates C₆H₅NHCSNH–(CH₂)_n–OPO₃Na₂ have been obtained by reacting phenylisothiocyanate with the corresponding aminoalkyl phosphoric monoester in the presence of 2 eq. of NaOH.     

Recherches sur la formation et la transformation des esters LXXVII [1]. Etude à l'aide de H2[18O] de la scission de quelques monoesters phosphoreux et de l'acide propargyl-benzènephosphonique

(1) Monopotassium phosphite KH₂PO₃ heated at 300°C with CO[¹⁸O] exchanges one atom of oxygen after 3 hours, one to two atoms after 6 hours, and its three O atoms after 12 hours; the probable mecanism of this exchange is discussed. When the same treatment is carried out in the presence of o-phenylene diamine hydrochloride, the exchange is total (three O) after 3 hours at 300°C. Treated by this last procedure, benzenephosphonic acid C₆H₅PO(OH)₂ undergoes equally a total exchange of its O atoms in 3 hours.     

Recherches sur la formation et la transformation des esters LXIV. Acides aminoalcoylsulfuriques et isothiocyanates: N-thiocarbamylation sans ou avec alcoylation cyclisante intramoléculaire

Aminoalkyl sulfuric monoesters with primary or secondary amino groups – with the exception of colaminesulfuric monoester – react with isothiocyanates in the presence of one equivalent of a base to yield the corresponding hydrosoluble salts of [N-aryl(aralkyl or alkyl)thiocarbamoyl]-aminoalkyl sulfates.     

Recherches sur la formation et la transformation des esters LXXIV [1] etude à l'aide de H2[18O] de la scission de quelques monoesters N-phénylthiocarbamyl(ou N-phénylcarbamyl)- aminoalcoylphosphoriques et de l'acide dibromo-2,3-allyl-phosphorique

The scission of some N-phenylthiocarbamoyl(or phenylcarbamoyl)-aminoalkyl phosphoric monoesters and of 2,3-dibromoallyl phosphoric monoester is studied in H₂[¹⁸O], at 100°C and at various pH.     

Recherches sur la formation et la transformation des esters LXXIII Sur la préparation d'acides ω-[aryl (ou aralcoyl ou alcoyl) carbamylamino]-alcoylphosphoriques et sur leur vitesse de scission à divers pH

N-Aryl(or aralkyl or alkyl)carbamoyl-aminoalkyl phosphoric monoesters have been prepared by the reaction of isocyanates R′-N?C?O on the corresponding amino-alkylphosphoric monoesters H₂N? R? OPO₃H₂ in the presence of 2 equivalents of NaOH. The rates of scission of the phosphoric monoester group and occasionally of the phenylcarbamoylamino group of these monoesters have been studied at 100°, in solutions 0.1M in ester and at various pH.     

Recherches sur la formation et la transformation des esters LXVII. Note sur la scission des acides ω-(N-phénylthiocarbamylamino)-alcoyl-sulfuriques à divers pH

In aqueous solutions at 100°C varying from HCl 2N to NaOH 2N , N-phenylthiocarbamoyl derivatives of aminoalkylsulfuric monoesters C₆H₅NH? CS? R? OSO₃H are split in the following ways:

• (a) With R = ? CH₂? CH(CH₃)? or ? (CH₂)₃? the scission of the monoester group is very rapid in the hole pH-range studied, especially in alkaline medium; the resulting cyclic products, 5-methyl-2-phenylamino-thiazoline and 2-phenylimino-tetrahydrothiazine respectively, formed by nucleophilic attack of an unshared pair of the S atom on the C bearing the monoester group, have been isolated and identified.
• (b) With R = ? (CH₂)₄? , the rate of the scission in alkaline or neutral medium is very much higher than that of an alkylsulfuric monoester; in these media a cyclic product is also formed (this time by nucleophilic attack of the unshared pair of the thiocarbamoylated N atom on the C bearing the monoester function) which has been isolated after alcaline scission, and identified as N-phenylcarbomoyl-pyrrolidine. In acid medium, no special influence of the phenylthiocarbamoyl group is observed.
• (c) With R = ? (CH₂)₅? or ? (CH₂)₆? , the rate of the scission in alkaline medium is 30 to 1000 times lower than in the previous cases; no pure organic scission products have been isolated. In acid or neutral medium, these two esters behave like usual alkylsulfuric acids.

     

Sur la réaction de reformatsky : I. Préparation et réactivité des organozinciques issus de divers crotonates d''alcoyles

Lithiation of (Me₃Si)₃CH by methyllithium (ether-THF) yields (Me₃Si)₃CLi and by t-butyllithium (C₅H₁₂-TMEDA) yields (Me₃Si)₂CHSiMe₂CH₂Li. Only starting material is recovered when (Me₃Si)₃CH is allowed to react with n-butyl- lithium (ether-THF and C₅H₁₂-TMEDA) and t-butyllithium (C₅H₁₂ and C₅H₁₂- THF). (Me₃Si)₄C is lithiated by t-butyllithium (C₅H₁₂-TMEDA) to give (Me₃Si)₃- CSiMe₂CH₂Li, but not by methyllithium (ether-THF and ether-THF-TMEDA). The structures of the lithiated compounds are based on the carbonation products. The above results are explained in terms of carbanion stability and steric effects. Spectral data are reported on the α-silylacetic acids.     

Sur le mécanisme de la réaction de meth-cohn-tarnowski de préparation des thiocoumarines

Reaction of 2-t-butylthiobenzaldehyde with N-(2-dialkylaminoethyl)-cyanacetamides followed by heating of the resulting 3-(2-t-butylthiophenyl)-2-cyanoacrylamides in polyphosphoric acid leads to the formation of 3-carboxamido-2-imino-2H-benzo[b][l]thiopyrann intermediates which afford thiocoumarins on hydrolysis. The authors postulate the intermediate formation of a thiophenate ion by an electronic mechanism involving six centers.     

Recherches sur la formation et la transformation des esters LXXXIII [1]. Réactions de condensation et/ou de phosphorylation,en solution aqueuse,de divers composés organiques à fonctions ?OH,COOH, NH2, ou autres, à l'aide de polyphosphates linéaires ou cycliques

Amino acids and other derivatives are condensed in aqueous solutions in the presence of linear or cyclic polyphosphates (or other anhydrides of P acids). The best results are obtained in slightly alkaline media (pH 7.5 to 9.5). The reaction, which has been studied at 70°C and at room temperature, proceeds with relative ease even at room temperature. In the case of the cyclic polyphosphates, trimetaphosphate gave the best results as compared with tetra- and hexametaphosphate, and among the linear polyphosphates used the yields grew with the average length of the chain. The significance of this method of condensation as a general method and also in the context of chemical evolution is discussed. The author suggests that one of the pathways leading to the peptide bond formation involves the intermediate formation of aminoacyl phosphates or polyphosphates by the nucleophilic attack of the carboxylate group of the amino acid on the phosphorus of a linear or cyclic P? O? P bond, giving rise to the labile mixed anhydride, and subsequent nucleophilic attack of the amino nitrogen of a molecule of the amino acid, or of the aminoacyl phosphate already produced, on the C of the mixed anhydride with displacement of phosphate or polyphosphate and formation of a peptide bond. Other pathways may also involve the intermediate formation of phosphoramidates which may result from the reaction of amino groups (or ammonia) with trimetaphosphate in alkaline medium. Linear and cyclic polyphosphates (which are known to be phosphorylating agents of the OH (alcoholic) function in aqueous solutions at pH's above 7) phosphorylate serine, ethanolamine and threonine in aqueous solutions at pH 8–10 with yields up to 25%.     

Régiospécificite et stéréosélectivite de la cycloaddition de l'oxyde de benzonitrile sur la phényl-5 A-3-pyrazoline

An example of stereospecific and stereoselective reactions is described concerning the cycloaddition of benzonitrile oxyde with 1,2-dimethyl-5-diphenyl-3-pyrazoline. The structure of the two epimeric 5,6-dimethyl 3,4-dimethyl[4,3-d]pyrazolidinoisoxazo-lines-2 was proved by the means of chemical and physical methods. The conversion of one epimeric product to another more stable is achieved and discussed.     

Recherches sur le benzofuranne,LVII. Sur une chloration inhabituelle de l'hétérocycle au cours de la réduction des (nitro-4 phényl)-2 ou -3 benzo-furannes par le chlorure stanneux

Reductions of 2-(4-nitrophenyl)- and 3-(4-nitrophenyl)benzo-furans by stannous chloride in presence of hydrochloric acid yield not only the expected 2-(4-aminophenyl)- and 3-(4-amino-phenyl)-2-chlorobenzofurans but also the 2-(4-aminophenyl)-3-chloro- and 3-(4-aminophenyl)-2-chlorobenzofurans the structures of which have been ascertained by their ¹³C nmr spectra, by comparison with those of 2-phenyl- and 3-phenylbenzofurans. These interfering chlorinations are most likely due to a radical mechanism.