Deshydratation du di-t-butylmenthylcarbinol dans l'acide acetique anhydre: Probleme de l'etape determinante

The products of the acid-catalysed dehydration of di-t-butylmethylcarbinol (1) in acetic acid are 2-t-butyl-3,3-dimethylbut-1-ene (2) and 2,3,3,4,4-pentamethylpent-1-ene (3). The rate constant for the rearrangement of 2 to 3 (k_rearr) is about 10 times smaller than that of dehydration (k_I). The kinetic isotope effect on the dehydration rate of d₃-methyl-(1) is that expected for a secondary isotope effect upon carbonium ion formation; there appears to be no primary kinetic isotope effect. The rate determining step is, then, probably heterolysis of the protonated alcohol, contrary to what is observed in aqueous media where carbonium ion deprotonation is rate determining. At low acidity (H₀ > - 1) the (log k_I)/ — H₀ correlation has a slope close to unity but at higher acidity log k_I increases faster than —H₀.     

Composes heteroorganiques—XLVII: Les arylsulphonamides de l'acide ethane-ethoxy-thiophosphonique

The synthesis, structure and properties of arylsulphonamides of éthane-éthoxy-thiophosphonic acid 1–6 are described. The compounds exist mainly in the amidothione form. In CCI₄ an equilibrium between monomers and molecules associated through hydrogen bonding is present. Thermodynamic functions of the equilibrium reaction have been determined and the results suggest that the associated molecules are cyclic dimers. The pK-values of 1–6 obey a combination of the Ismajlow-Hammett equations.     

Synthese de derives de la tobrosamine par addition d'acide hydrazoique sur un systeme enonique dans la serie hydrate de carbone

Derivatives of a new diaminotrideoxy-d-ribo-hexopyranose, a component of the antibiotic tobramycin, have been prepared by addition of the elements of hydrazoic acid to the α, β-unsaturated ketone 8. After 5 min only the kinetically favored product 13 was observed, which is gradually transformed into the thermodynamically more-stable substance 20. The equilibrium mixture after 5 hours contained d-erythro and d-threo isomers 20 and 13 in the ratio 6:4 The d-erythro azide 20 was converted into the derivatives of di-N-acetyl tobrosamine.     

Nouvelle transposition du squelette aspidospermane: reactivite de la chloro-16 dehydro-1 vincadifformine dans l' acide acetique

Heating of 16-chloro 1-dehydro vincadifformine 4a in pure acetic acid yields mainly the new compound 5 by a fragmentation-rearrangement sequence. Structure of 5 was studied by spectroscopic methods and it has been determined by X-ray crystallography of its reduction N-methylation derivative 8. The proposed mechanism for the formation of 5 is confirmed by a mass spectrometry study.     

Degradation bactérienne de l'acide dehydroabiétique par Flavobacterium resinovorum

Flavobacterium Resinovorum was grown on dehydroabietic acid 1a as sole carbon and energy source. Slowly growing cultures were obtained either by omission of nitrogen, Fe²⁺ and Mg²⁺ ions or in the presence of an inhibitor (α,α′-dipyridyle). Under these conditions, different intermediates of the metabolic pathway were accumulated. Diphenol diketone 6a has been isolated. The unique behaviour of bacterial attack at C-3 before the degradation of the cyclic system is confirmed.     

Etude par rmn de31p de la reaction de l'hexamethylphosphotriamide avec le trichlorure de phosphoryle

The reaction of HMPT with POCl₃ was studied by ³¹P NMR at various temperatures and stoechiometries. Progressive substitution of chlorine atoms of phosphoryl chloride by HMPT molecules was observed. Six new species were involved in the system. The main produce was the $\text{1}\text{1}$ adduct, (Me₂N)₃P⁺Cl, O₂PCl₂^?, analogous to Vilsmeier complex.     

Syntheses totales et etudes de lignanes biologiquement actifs—6: Syntheses totales de la (±)-iso-β-peltatine et de ses analogues

2-Benzyloxypiperonal 15, a key intermediate in our synthesis of (±)- iso - β - peltatin 7, was obtained by bromination of 4 - hydroxy - 1,3 - benzodioxole 12, followed by treatment with (i) excess n-BuLi,o li]N-methylformanilide, li]HCl/H₂O, and li]benzyl chloride/K₂CO₃. The aromatic aldehydes 15 and 6 were subsequently transformed into the corresponding β - (2 - alkoxy 3,4 - methylenedioxybenzyl) -γ- butyrolactones 19 and 29, respectively. α-Hydroxyalkylation of 19 with 3,4,5-trimethoxybenzaldehyde 20, followed by cyclisation and hydrogenolysis afforded (±)- iso -β- peltatin 7 in good yield. Similarly, α-hydroxyalkylation of 29 with 20 and syringaldehyde 21, followed by cyclisation, afforded good yields of (±)- iso -β- peltatin O-methyl ether 5 and (±)-iso-α- peltatin O-methyl ether 8, respectively.     

Preparation et proprietes de quelques sulfures de phospholes fonctionnels

^tBuLi with 1-phenyl 3,4-dimethyl phosphole sulfide 1 in THF, gives a mesomeric anion 4. With aldehydes and ketones, this anion leads to methyl-substituted phospholes (6 and 9), 2-substituted phospholes (8) or 2-substituted 3-methylene phosphol 4-enes (5 and 7). With CO₂ and CH₃COOEt a 2-phosphole carboxylic acid 11 and a 2-acetyl phosphole 10 are obtained, respectively. The spectra of the 2-substituted phospholes are studied in some detail. Some of their chemical properties (dimerization, dissociation and tert-butylation) are also described.     

Synthese de derives de la purpurosamine C,composant de la gentamicine C1a

The synthesis of derivatives of purpurosaimine C and epi-purpurosamine C is described, from methyl 2,3,4,6-tetra-O?-methylsulphonyl-α-d-galacto and glucopyranosides 2 and 3 by reaction with azide ion to give diazides 4 and 5, transformed in a series of reactions via epoxides 6 and 7 into the corresponding olefines 16 and 17, thermal rearrangement to give diazides 18 and 19, which were transformed into the methyl glycosides 27 and 29 and mercaptolysis with ethanethiol followed by N-acetylation, gave 2,6-diacetamido-2,3,4,6-tetradeoxy-d-erythro-hexose diethyl dithioacetal 30 (identical with authentic 30 prepared from gentamicin C_1a)and 2,6-diacetamido-2,3,4,6-tetradeoxy-d- threo-hexose diethyl dithioacetal 31, an enantiomer of a mercaptolysis product of dihydrosisomicin.     

Photocycloaddition des hydrocarbures aromatiques polynucleaires en solution—iv: Etude de la fluorescence et de la photoreactivite de l'acenaphtylene et du cyano-1 acenaphtylene

The fluorescence of acenaphthylene follows a Stern-Volmer relationship in air-saturated ether giving a self-quenching constant K_F=0.12M^?1, indicating that the syn photodimer originates from the singlet state of acenaphthylene. By comparison, 1-cyanoacenaphthylene undergoes a more efficient self-quenching (K_F= 2.8 M^?1) in air-saturated ether. No excimer fluorescence was detected for 1-cyanoacenaphthylene nor the parent compound in solution. The triplet state of 1-cyanoacenaphthylene, obtained by sensitization or induced by heavy atom solvent (EtI), was shown to generate exclusively the head-to-head anti photodimer in a high chemical yield. Regiospecificity and stereospecificity observed in this reaction indicates the influence of the acenaphthylenic ring and the cyano group in stabilizing the diradicaloïd transition state.     

Isolement de l'acide 3-amino 12-methyl tetradecanoique et de l'acide 3-amino 12-methyl tridecanoique a partir de l'iturine,antibiotique de Bacillus subtilis

lturin, a peptide antibiotic from Bacillus subtilis, was separated into three iturins: A, B, C by thin-layer chromatography. Iturin A, which has an antifungal activity, contains Asp, Glu, Tyr, Ser, Pro in a molar ratio 3:1:1:1:1 and a lipid moiety AL. The latter was shown to be a mixture of C₁₄ (40%) and C₁₅, (60%) amino-acids. The structure of these was determined by combined gas chromatography-mass spectrometry of the N-acetylmethyl esters. Strong peaks at m/e = 144 and m/e = 102 indicate a β-amino group. Identification of acetone and methylethylketone after chromic acid oxidation indicates an iso and anteiso structure. After comparison of the natural amino-acids with synthetic 3-amino pentadecanoic acid it is concluded that the lipid AL is a mixture of 3-amino 12- methyltetradecanoic acid and 3-amino 12-methyltridecanoic acid.     

Reactivite des derives organomanganeux—VIII : Préparation de cétones par acylation d'organomanganeux. Influence de la nature de l'agent acylant,des solvants et des ligands

The influence of the nature of acylating reagents, solvents and ligands on the preparation of ketones by acylation of organomanganous reagents is studied. Thus acid chlorides in ether, symmetrical acid anhydrides in ether or THF and mixed carboxylic-carbonic anhydrides (R'COOCOOEt) in ether are compared, they lead to the corresponding ketones with good or excellent yields. Some problems of reproductibility are encountered and discussed when mixed anhydrides R'COOCOOEt are used in THF. The addition of a great variety of cosolvents (e.g. C₆H₆, AcOEt, CO₃Et₂, CH₂CN, CH₂CL₂, . .) to the reaction mixture before addition of the acylating reagent does not affect the yield of ketones. In comparison the complexation of organomanganous reagents by several ligands (e.g. Me₂S or Ph₃P) has no subsequent effect on their acylation. The main limitation for the choice of solvents or ligands is the use of amino derivatives which generally lead to a very low yield of ketones (e.g. C₅H₅N, TMEDA, Et₃N) or unreproducible yields (e.g. HMPA). Two applications of these studies are described:The stabilization of s or t-alkyl manganous derivatives by complexation which leads to the best yield of the corresponding ketonesThe use of a cosolvent in order to increase the yield when mixed anhydrides R'COOCOOEt are used in THF.     

Alcaloïdes indoliques—CIII: Préparation de dérivés de l'hétéroyohimbane à partir de la corynanthéine. Réactivité de l'enchaînement MeOOC-CHCHOR vis-à-vis de la double liaison vinylique activée par mercuration

The reactivity of the MeOOC-CHCHOR group (R = H or Me) or demethyl-corynantheine 1 and corynantheine 26 towards the vinylic double bond activated by mercuration is studied. In the presence of Hg(OAc)₂ in warm AcOH the mercurinium ion derived from 1 undergoes both a non-stereoselective Markovnikov attack by the enolic oxygen and an anti-Markovnikov attack by the activated C-16 methine leading to a mixture of 2a,3a and 4a after demercuration. In the presence of Hg(OCOCF₃)₂ in aq THF or MeOH, 1 gives mainly ,19α-H cyclic hemiketals and ketals. It is assumed that the stereoselectivity of the reaction is due to the formation of the intermediate oxonium 25 leading to the more stable epimer. In the same conditions (aq THF) 26 reacts as a hemiketal MeOOC-CH₂CH(OH)OMe affording essentially a mixture of cyclic ketals. These ketals, on treatment with PPA, give ajmalicine 2a and 19-épiajmalicine 3a.     

Selectivite de la reduction de l'androsten-4 dione-3,17 et de la progesterone par divers borohydrures: role de l'assistance electrophile par le cation ou un solvant hydroxyle

The reduction of Δ⁴-androsten-3, 17 dione 1 and of progesterone 2 by nBu₄NBH₄ is highly chemioselective: in THF only the a-enone moiety is reduced, the saturated C₁₇ or C₂₀ keto group being kept unchanged. When TMEDA is added, saturated alcohols are obtained, without any allylic alcohol when the reaction goes to completion. However this reduction is poorly stereoselective as 70:30 mixtures of A/B cis and trans ring junction compounds are obtained. In MeOH, the saturated keto group is more than 90% selectively reduced. However, the reduction of 1 and 2 by LiBH₄ and Zn(BH₄)₂ is poorly chemioselective. These results are interpreted in terms of competition between electrophilic assistance and steric effects.     

Synthese totale de la (±) negamycine

A total synthesis of (±) negamycine 1 has been achieved in 14 steps from the acrolein dimer 6, which possesses the same carbon skeleton as the key intermediate lactone 4. Treatment of 2-acetoxymethyl 3,4-dihydro[2H]pyran 8, obtained from 6, with lead tetracetate gave the allylic hemiketal 15, which was converted into the corresponding anomeric methyl ethers 23. Hydroxylation of the double bond of 23 with mercuric acetate, occurred selectively at the γ-position and the resulting isomeric alcohols 24 were isolated as their dimesylates 25a and 25b. Condensation of sodium azide with the (trans-derivative 25a resulted in the formation of the cis-diazide 26a by inversion of configuration at C₃. Hydrogenation of 26a followed by acetylation of the intermediate diamine gave the cis-diamide 28 having the required stereochemistry. Oxidation of the corresponding hemiketal 29 by means of silver silicate yielded the diacetamido-lactone 4, which was then hydrolysed into (±) δ-hydroxy β-lysine 2 by refluxing aqueous HCl. Under the conditions required to protect the amino-groups as benzylcarbamates, the lactone 30 was produced. However, 30 gave directly the hydrazine 36 by condensation with benzyl N-methyl-hydrazinoacetate in refluxing acetonitrile m the presence of SiO₂. Finally (±) negamycine was obtained by hydrogenolysis of the protecting groups of 36. The antibacterial activities of the racemic antibiotic have been compared, in vitro and in vivo, with those of the natural product and with gentamicine C.     

Cinetique complexe de l'halogenation de cetones en milieu acide—I : Iodation des enols

The kinetics of the iodination of acetone, diethylketone and di-isopropylketone in aqueous media ([H₂SO₄] = 0·1 to 1·0 N; [I₂]_a^o = 10^?7 to 10^?5M) have been studied by couloamperometry under irreversible conditions. At these concentrations the rates of formation of the enol and of its iodination are similar. The general equation, which assumes the steady state approximation for the enol, is applicable, and is used to separate the rate constants of enolisation (k₁) and the apparent enol iodination rate constant (k_II^I₂ = K_Ek₂^I₂). For acetone, the value given by Schwarzenbach for the enol equilibrium constant (K_E = 2·5 x 10^?6) leads to an elementary rate constant for the addition of iodine to the enol (k₂^I₂ = 6·5 x 10⁶ M^?1s^?1). This value is not, however, consistent with k_I2 = 1·5 x 10⁸ M^?1s^?1, the rate constant for the iodination of the corresponding ether 2-ethoxypropene.     

Selectivite de la reduction de cyclohexen-2 ones par NBu4BH4 dans divers solvants et par NaBH4 dans des conditions de transfert de phase

The 2-cyclohexenone 1 and isophorone 2 reductions with NBu₄BH₄ in aprotic solvents lead to a highly preferential 1–4 attack; i.e. 85% with 1 and 96% with 2 in THF. These regioselectivities are nearly the same as those observed with LiBH₄ in the presence of[2.1.1) cryptand confirming thus the cation influence. This method which is inexpensive and easy to work up, seems to constitute a general way to reduction of α-enones to saturate alcohols while other reagents such as K(sec Bu)₃BH are not able to reduce the carbon-carbon double bond of isophoron.Phase transfer catalysis conditions are not useful for selective reduction: large amounts of allylic alcohols are formed in liquid-liquid phase transfer conditions (60% in toluene-water); a good regioselectivity is only obtained when a cryptand is used as a transfer agent in solid-liquid conditions.     

Etude thermoanalytique de substances psychotropes. IV. Lorazepam et oxazepam

We have studied the thermal behaviour of lorazepam (a) and oxazepam (b), defined the crystal form and the thermal stability. After recrystallization in several solvents under known temperature and pressure conditions the thermoanalytical study of samples has shown polymorphs for (a) and (b) and pseudopolymorphs for (a), (a) Polymorphs are I (t_f = 183°C), II (T_f =173°C), III (T_f =170°C). IV (_Tf, =163°C), V (_Tf =158°C), VI (_Tf, =153°C), and seven pseudopolymorphs, three of which are clathrate type of 1:1 molar composition with propanol, chloroform and isopentanol. We have found eight polymorphs for (b): I (T_f = 207°C), II (T_f=201°C), III (T_f=193°C), IV (T_f=189°C). A, B, C and D show a solid ? solid transition. Commercial samples of (a) are form I, those of (b) are form II.A spectral and dissolution kinetic study completes the thermoanalytical results in relation to biological availability.     

Le mécanisme de l'hydrolyse acide des aryl-diazométhanes

In the acid catalysed hydrolysis of three monoaryl-diazomethanes (p)-nitrophenyl-diazométhane (I), p-chlorophenyl-diazomethane (II), phenyl-diazomethane (III), absence of exchange H-D, solvent isotope effects about 2,6, and general acid catalysis prove that proton transfer is rate determining (A-S_E2 mechanism). Like other A-S_E2 reactions, the hydrolysis of I is shown to obey the Brønsted catalysis law with a variety of carboxylic acids; for eight of these acids, α_B was found to be 0,69 ± 0,06.     

Influence des associations moleculaires sur la copolymerisation de l'acide acrylique avec l'acide methacrylique et avec l'acrylate de methyle

The copolymerization of acrylic acid with methacrylic acid in bulk is investigated at 40 and 60°. It is confirmed that a “matrix effect” occurs only for high contents of acrylic acid. The critical concentration beyond which the matrix effect disappears is shifted towards lower acrylic acid contents for higher temperatures. The copolymer composition is independent of temperature. The copolymerization of acrylic acid with methyl acrylate is investigated in a mixture which determines an “exaltation of the matrix effect” in the homopolymerization of acrylic acid (molar fractions: m_Monomers = 0.34; m_n-Hexane = 0.52; m_Methanol = 0.14). The resulting copolymers are found to contain a much larger fraction of acrylic acid residues than the copolymers formed in bulk or in toluene or DMF solutions.