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 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 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%.     

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 LXXXI [1]. Sur la réaction d'isothiocyanates avec l'acide hydrazinoéthylphosphorique,et de l'isocyanate de phényle avec l'acide colaminephosphoreux

Hydrazinoethyl phosphoric monoester has been prepared by reacting hydrazinoethanol with polyphosphoric acid, and isolated as di-sodium salt. Sodium hydrazinoethyl phosphate reacts with phenylisothiocyanate (in H₂O+ethanol) to yield mainly the derivative thiocarbamoylated at the substituted nitrogen atom. This derivative, heated for one night at 100° in 0.5 N HCl, is cyclized to 3-amino-2-phenylimino-thiazolidine in 62% yield. Sodium hydrazinoethyl phosphate reacts with o-methoxycarbonylphenyl isothiocyanate (in H₂O+dioxane) at the unsubstituted nitrogen atom to yield mainly the corresponding quinazoline derivative (IV, X = OPO₃Na₂). This derivative, heated for one night at 100° in 0.5 N HCl, is cyclized to 2-o-carboxyphenylamino-dihydro-δ²-1, 3, 4-thiadiazine (Va) in 55% yield (hydrolysis of the lactamic function as well). Aminoethyl phosphorous monoester (colaminephosphorous acid) reacted with phenylisocyanate (in H₂0+dioxane) in slightly alkaline medium (one equivalent of NaOH) yields sodium N-phenylcarbamoylaminoethyl phosphite. Refluxed for 20 minutes in 1N NaOH, this carbamoyl derivative is not cyclized but only hydrolyzed to the open-chained N-phenyl-N′-hydroxyethylurea (VII).     

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.

     

Addition de la proline à quelques alcènes et alcynes électrophiles

Addition of proline in acetic anhydride to propiolic and pbenylpropiolic ester gave rise to two isomeric pyrroles 5 and 6 . Addition under the same conditions, to electrophilic alkenes pY-PhCH = C(X) (CN) led to a pyrroline-2 8 which eliminated HCN and produced pyrrole 9 . Addition of proline to fumarodinitrile is unusual, the reaction led to a new α-amino acid 10 and compound 11 . The structure of this product 11 was confirmed by X-ray measurements.     

Recherches sur la formation et la transformation des esters LXXII. Aryl(ou aralcoyl ou alcoyl)amino-2-tétrahydro-m-thiazines ou aryl(ou aralcoyl ou alcoyl)amino-2-dihydro-Δ2-m-thiazines et dérivés

3-Aminopropanol reacts with aryl(or aralkyl or alkyl)isothiocyanates R? N?C?S to yield the corresponding thio-ureas R? NH? CS? NH? (CH₂)₃OH which, refluxed with hydrochloric acid, are cyclized by elimination of water. The cyclization products are identical with the hydrothiazines resulting by elimination of sulfate or phosphate from the sulfuric or phosphoric monoesters of these thio-ureas. The resulting hydrothiazines are either 2-(R-imino)-tetrahydro-m-thiazines (I) or 2-(R-amino)-dihydro-Δ²-m-thiazines (II). Their structure has been established by comparison of their spectra with those of model compounds in one of which the C?N double bond is certainly endocyclic (2-methyl-dihydro-Δ²-m-thiazine), the other presenting an exocyclic C?N double bond (3-methyl-2-phenylimino-tetrahydro-m-thiazine). When R is an aryl group, the C?N double bond is exocyclic (structure I with >C?N? Ar), and one may presume that this structure is stabilized by resonance. When R is an aralkyl or an alkyl group, the C?N double bond is endocyclic (structure II). The nmr spectra were taken with three types of solvent: CDCl₃ or CCl₄; (CD₃)₂SO; CF₃COOH. In CF₃COOH solution the benzylic protons of the hydrothiazine with R = pF? C₆H₄CH₂? couple with NH (J=5,5cps) which confirms the endocyclic position of the C?N double bond in this case.     

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 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.     

Note sur la préparation et la scission de l'acide (diméthyl-3, 3-butyl)-phosphorique

3,3-Dimethylbutanol treated with polyphosphoric acid or with an equimolecular amount of POCl₃ gives rise to 3,3-dimethylbutyl phosphoric acid, isolated as baryum salt (yield 20 to 30%) or as sodium salt (yield 15%). Stable in NaOH 1N at 100°C, this monoester is split at pH 4.5 and in HCl 1N much slower than choline phosphate.     

Détermination du Site de Protonation de l'Azido-2 thiazole et du Thiazolo[2,3-e]tétrazole à Partir de la Largeur des Raies des Signaux Protoniques

The signals of protons bonded to carbon atoms in α position to the pyridinic nitrogen atom in thiazole and in γ position in thiazolo[2,3-e]tetrazole are broadened. This broadening disappears on irradiation at the ¹⁴N resonance frequency, on cooling, and in an acidic medium (in which the protonation sites in both molecules can be determined).     

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).