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 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 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.

     

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 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 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 LXXXII [1]. Sur la différenciation entre structures δ2-amino-2 ou imino-2 dans des composés S,N-hétérocycliques pentagonaux et hexagonaux à cycle par ailleurs saturé

Comparison of the NMR. spectra in CDCl₃ of the heterocyclic bases obtained from the cyclisation of ω-(N-thiocarbamoylamino) ethyl (or propyl)-alcohols (or their orthophosphoric or sulfuric monoesters) to those of model compounds II (n = 1 or 2) and III (n = 1 or 2) has shown that: (1) In the case of five membred rings the C?N double bond is always endocyclic (Ib, n = 1) should R be aromatic, araliphatic or aliphatic; (2) In the case of six membered rings the C?S double bond is cnclocyclic when R is aliphatic or araliphatic (Ib, n = 2), and exocyclic when R is aromatic (I a, n = 2), with the exception of 2-(o-carboxyphcnylamino)-dihydro-δ²-m (Ib, n = 2, K = o-carboxyphcnyle). In CF, COOH, all five membered rings (I b, n = 1) show a triplet for the C-4 methylenic protons, whereas all the six membered rings (Ia or I b, n = 2) with the exception of I b, n = 2, R = o-carboxyphenyle, are represented b y a double triplet for the C-4 protons (samt. protonated spccics). Only one triplet is observed when the 3 position is substituted. Thiocarbamoylation of hydrazinoethanol or its orthophosphoric or sulfuric monoesters canoccur at either of the two nitrogen atoms, thus yielding upon cyclization five- (IT′) or six-membered rings (Va or Vb). The NMR spectra of compounds I V in (CIl,), SO show a singlet for 2 amino pro-tons (3-amino) and there is no further structural problem. The NMR spectra of compounds T′ in (CT), SO show a triplet for one amino proton coupling with the neighboring methylenic protons. I n this case, mode1 compounds are needed to assign the position of the C?N double bond ( e x cyclic V a or cndocyclic V b). When R = o-carboxyphenylc, the C?N double bond is probably endoc, yclic (Vb) because this ccimpound and 2-(o-carboxyphenvlarnino)-dihydro-δ² have very similar UV spectra.     

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).     

Réactions du diazométhane III. Etude de la réaction d'insertion entre diazométhane et phénylcarbamates: comportement de la N-(phénoxy-carbonyl)-aniline et de la N-(p-nitrophénoxy-carbonyl)-aniline

Diazomethane reacts with N-(p-nitrophenoxy-carbonyl)-aniline giving on the one hand p-nitroanisole and phenylisocyanate, the latter being transformed into N-phenyl-β-propiolactam, and on the other hand N-(p-nitrophenoxy)-acetanilide by insertion. N-(phenoxy-carbonyl)-aniline does not react. The insertion reaction seems to depend on the heterolysis of the bond between the oxygen of the p-nitrophenoxy group and the carbamic carbonyl function, which is strongly polarized (existence of a mesomeric nitro-phenoxonium). The insertion is equally influenced y the nature of the radical R attached to the carbamic nitrogen: with R = ? CH₂COOC₂H₅ the reaction yields only isocyanate, with R = ? C₆H₅ it yields at the same time the isocyanate and the insertion product.     

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).     

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.     

Addition de l'Hexafluoroacétone sur les Acides Carboxyliques—Mise en Évidence par RMN 1H et 19F. Application à l'Analyse d'un Mélange d'Acides

The compound HO? C(CF₃)₂? O₂CR results from nucleophilic addition of a carboxylic acid to the carbonyl group of hexafluoroacetone. I.r. and n.m.r. (¹H, ¹⁹F) spectroscopy have been used to show that the addition is reversible. The addition is favoured by a lowering of the temperature and by the use of acids in which the group R is electron donating. Moreover, the chemical shift of the CF₃ groups (or of the OH group) in the addition product is dependent on the nature of R. Thus, this reversible addition can be used as a method for the analysis of a mixture of carboxylic acids by n.m.r. spectroscopy.     

Etude par Résonance Magnétique Nucléaire du carbone 13 de complexes du cobalt (III) et de la diméthylglyoxime

From a carbon magnetic resonance study of several alkylcobaloximes RCo(DMG)₂B (DMG = dimethylglyoximate monoanion), it was possible to estimate the α, β and γ effects of the Co(DMG)₂B group on the chemical shifts of the carbon atoms of various alkyl groups R. The chemical shifts of the carbon atoms belonging to the equatorial ligands and to the axial base B are not significantly affected by structural modification of the R groups. Values of δ in benzylcobaloximes XC₆H₄CH₂Co(DMG)₂B agree with a donor effect of the ? CH₂Co(DMG)₂B radical. Values of ¹J(¹³C? H) coupling constants, measured in ¹³C enriched methylcobaloximes, do not vary appreciably when B is changed (J(¹³C? H) = 137 ± 1 Hz) and are close to the value obtained for methylcobalamine.     

Complexation du trichlorure d'aluminium par la triméthylphosphine et la diméthylphénylphosphine: Etude RMN

NMR spectra of several R₃P/AlCl₃ systems [with R₃ = (CH₃)₃ and (CH₃)₂(C₆H₅)] in solution have been measured. The results suggest the occurrence of fast exchanges involving 1/1 and 2/1 adducts and free phosphine. The existence of the 2/1 compounds has been confirmed by low temperature (173 K) experiments.     

Etude par Spectrométrie de Masse de Silanes et de Stannanes Aromatiques

The mass spectra of six compounds of the type Et₃Si? C₆H₄? ZR_xR_3?x (R=Et, R′ = CI, Z = Si, Sn) have been measured. The fragmentation patterns can be interpreted on the basis of an ionized hexa-1,3-diene-5-yne intermediate.     

Recherches en série diazépine-1,4 et triazépine-1,2,4. X. Réductions et méthylations de pyrazolo[3,4-b]diazépines-1,4

Reduction and methylation of pyrazolo[ 3,4-b ]diazepines have been effected by several methods. According to the reducing agents used, it has been possible to reduce selectively the C?N double bond, the carbonyl group, to reduce the diazepinone rings completely and to reduce partially or completely the insaturated parts of the (6H)pyrazolodiazepines. Methylation on the amide nitrogen, on oxygen of the same function, and in a few cases on the C₆ carbon of the pyrazolodiazepinones and finally on the 4 position in tetrahydropyrazolodiazepinones have been obtained.     

Etude calorimetrique et analytique de l'adsorption du cyanogene sur la silice

The adsoprtion of C₂N₂ on well outgassed specimens of SiO₂ at temperatures from 35 to 913°C has been studied by heat flow calorimetry, volumetry, and mass spectrometry.Small amounts of cyanogen are adsorbed at low temperature: reversibly by hydrogen bonding with the silanol groups, and irreversibly on strained siloxane bridges or Lewis acid sites. Above 200°C cyanogen reacts, with silanol groups, leading to the formation of HCN (partly reversibly adsorbed on non-reacted silanol groups) and silyl isocyanate:

. The process is complete at 418°C and the measured enthalpy for the reaction

is ΔH = ?12.2 ± 0.3 kcal mole^?.Above 500°C, HCN and C₂N₂ react with ordinary siloxane bridges. At higher temperature, the pyrolysis of

produces CO₂ with CO and N₂ (in smaller quantities), showing that a large proportion of N-atoms are bonded on the surface.     

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.     

Etudes sur les composés organométalliques V [1]. Action de la pyridine sur les organomagnésiens

By the action of pyridine on various Grignard reagents at room temperature, new diorganomagnesium complexes R₂Mg · 2pyridine (R=Ph, n-Bu, t-Bu and Et) were prepared and analyzed. Anomalous results were obtained with methyl- or benzylmagnesium reagents.     

Etude de la régiosélectivité de l'action des organozinciques sur les α-iminoesters issus de 2-amino ou 3-aminoalcools I. Synthése d'α-aminoesters polyfonctionnels

The preparation of some α-iminoesters R′N=CHCOO-t-C₄H₉ with R′ bearing an alcohol group has been studied; organozinc compounds prepared from allylic or propargylic bromides and from α-bromoesters or α-bromoamides react regiospecifically with these α-iminoesters to give polyfunctional α-aminoesters.