Polycondensation of (NPCl2)3 with Bifunctional Reagents

Abstract

The reaction of hexachlorocyclotriphosphazene and hydroquinone in the two-phase solvent system tetrahydrofuran/aqueous NaCl-NaOH solution leads in the beginning of the polycondensation to a mixture of oligomers with formula N₃P₃Cl₅-[P-OC₆H₄O)-N₃P₃Cl₄]_n-(p-OC₆H₄)-N₃P₃Cl₅. The first compound (n=0) in this series could be isolated in a pure state. Two others have been identified by spectroscopic methods. As expected, the addition of a phase-transfer catalyst (Bu₄NBr) accelerates the polymerization reaction. In addition to the oligomers mentioned before two isomers with formula N₃P₃Cl₄-(p-OC₆H₄O)₂-N₃P₃Cl₄ were formed in the reaction mixture together with large amounts of polymeric material. One of these isomers was obtained as a pure compound in a very low yield. The X-ray crystal structures of N₃P₃Cl₅-(P-OC₆H₄O)-N₃P₃Cl₅ and N₃P₃Cl₄-(P-OC₆H₄O)₂-N₃P₃Cl₄ will be compared. The structural data in combination with ³¹P NMR data of various reaction mixtures provide some clues for the structure of the polymers, formed ultimately. The reaction pathway during the polycondensation will be discussed and compared with that of the polycondensation of (NPCl₂)₃ with p-phenylenediamine.     

Octahedral Titanium(IV)-Reagents in Organic Synthesis

Abstract

As part of our studies directed toward the use of organotitanium chemistry in organic synthesis^1,2 we wish to report that stable hexa-coordinate octahedral complexes³ of methyltitaniumtrichloride (1) are diastereoand enantioselective methylating reagents. The reaction of tetramethylethylene diamine³ (TMEDA), glyme³ tetrahydrofuran³ or (?)-sparteine with the equivalent amount of 1 in CH₂Cl₂ yields compounds 2, 3, 4 and 5 respectively. These were allowed to react in situ with 2-phenylpropionaldehyde at ?50 °C in CH₂Cl₂ for two hours.     

Asymmetric Synthesis of Phosphinous Tungsten Complexes

Abstract

The asymmetric synthesis of phosphinous compounds from diheterophosphacycloal kane-1,3,2 was investigated in a transition metal complex series. Complexes 1 and 2 were prepared from diaminophosphine, (?)-ephedrine and W (CO)₅ THP (1: δ³¹ P=+147,6 ppm; J_PW=313 Hz M^.+=595;2 δ³ p=+156 ppm J_PW=304 Hz M^.+=533; 90%dp) in two steps. Methyl lithium reacted with 1 to give stereospecific 3 (83%Yield) by P-O linkage (3 δ³¹ P=+64 ppm; J_PW =261 Hz; M^.+ ? 28=583). The aminophosphine complex 3 was stereochemically stable and was used for studies of synthetic applications. HCL gas reacted with 3 in CH₂Cl₂ to give the non optically active chlorophosphine complex 4 (δ³¹ P=+103,6 ppm; J_PW=290 Hz; M^.+ =482). This compound immediately gave salt 6 (δ³¹ P=+66,7 ppm; J_PW =240 Hz) by reaction with (?)-menthol and triethylamine. The acid methanolysis of 3 gave a mixture of 5 and 6 and the unchanged (?)-ephedrine salt [5:30% yield; δ³¹ P=+114 ppm; J_pw=280 Hz; [α]_D=+1,2° (CH₂Cl₂); M^.+=478; 6 : 60% yield; δ³¹p=+102,9 ppm; J_PW=264 Hz; [α]_D =+16,9° (CH₂Cl₂); M^.+=464]. Compound 6 was thus obtained with a 80% yield and a specific rotation of + 20,2° (CH₂Cl₂) in isopropanol/H₂SO₄ 5M medium. The enantiomeric excess of 6 was determined by RMN³¹P. Acid hydrolysis of 3 or the reaction with CH₃SO₃H, gave phosphinous acid complex 6 with an optical rotation of + 4,8° or ?1,8° respectively. These results provide precious informations about the stereochemistry and reactivity of the P-N linkage in this aminophosphine transition metal series, which differs notably from that of the corresponding (PO) N bond.     

Synthesis of Dialkyl Phosphoroselenocyanatidates and Their Rearrangement to Dialkyl Phosphoroiso-selenocyanatidates

The synthesis of diaryl and dialkyl phosphoroisoseleno-cyanatidates (I) has been described only recently^1,2. However, their isomers, dialkyl or diaryl phosphoro-selenocyanatidates (II) are, to our knowledge, unknown. In our attempts of their synthesis we found that the preparation of II in the way analogous to the synthesis of the corresponding thiocyanatidates ³was not possible due to the inaccessibility of the 0,0-dineopentoxy-oxo-phosphoraneselenenyl chloride (III). Reaction of triethylamminium 0,0-dineopentyl-phosphoroselenoate (IVa) with sulphuryl chloride at -70[ddot]C in CH₂Cl₂ solution led     

The Synthesis of Hydronaphthalenes from m-Toluic Acid via Cyclization of Thioacetal Monosulfoxides

We recently developed a convenient route to hexahydronaphthalenols such as 5 (R=CO₂CH₃ or CH₃) starting from m-toluic acid (1)¹. The key features of the route involved reduction-alkylation of the toluic acid to the dihydro derivative 2 ², subsequent deprotection and oxidation of the side chain primary alcohol, and acid-catalyzed cyclization of the resulting aldehyde 4. In the case of the dimethylnaphthalenols 5 (R=CH₃), conversion of the angular carboxylic function to the methyl group was effected prior to cyclization via reduction of the p-toluenesulfonic ester of the neopentyl alcohol 3 (R=CH₂OH) using lithium triethylborohydride³.     

An Improved Synthesis of Ethyl Azodicarboxylate and 1,2,4-Triazoline-3,5-Diones Using Hypervalent Iodine Oxidation

ARSTRACT: Hypervalent iodine oxidstion of 1,2-dicarhethoxy hydrazine (1) and 4-substituted urazoles (3) using iodobenzene diacetate or pentafluoroiodobenzene bis-trifluoroacetate in CH₂Cl₂ at room temperature proceeds smoothly to yield ethyl azodicarboxylate (2) and 4-substituted 1,2,4-triazoline-3,5-diones (4) in excellent yields.     

The structure of cis and trans lsomers of 1-(p-Bromobenzylidene)-2-indanone

Abstract

In this communication we wish to report an interesting case of the isolation and characterization of the cis and trans isomers of 1-(p-bromobenzylidene)-2-indanone and their ketals. Prior to this work, Hoogstreen and Trenner² had reported on the cis and trans isomers of 1-(p-chlorobenzylidene)-2-methyl-5-methoxyindenylacetic acid. The condensation of 2-(N-morpholinyl)-indene (1, prepared by the reaction of 2-indanone³ and morpholine) with P-bromobenzaldehyde was conducted by refluxing them in the presence of acetic acid for 4 hours. Acid hydrolysis of the reaction mixture followed by dry column chrcmatography over sillica gel using a fraction collector afforded two iscmeric monobenzylidenes, compounds 2(36.6%, mp 110–111°)and 3(1.3%, mp 115–116°) and a dibenylidene, compound 4 (8.7%, mp 205°). The relative rations of the mono- and dibenzylidenes seemed to depend on the reaction conditions. Higher yields of the monobenzylidenes 2 and 3 were obtained by conducting the reaction in the presence of UV light. The structures of these monobenzylidenes were established as cis and trans isomers of 1-(p-bromobenzylidenes)-2-indanone on the Basis of elemental analyses and ir and nmr spectroscopy. The ir spectra⁴ (CHCl₃)

of compounds 2 [1725 (c=0), 1620 (c=c)cm^?1] and 3[1710 (c=o), 1570, 1600 (c=c) cm^?1] were consistent with the structures. The molecular ion peaks as well as the fragmentation patterns in the mass spectra of both these compounds were consistent with the assigned structures. Before going into the omr discussion it should be pointed out that treatment of compound 2 with athylene glycol in the presence of p-toluene sulfonic acid produced two ketals, 5 (38.3% mp, 118–120°) and 6 (30.6% mp, 125–126°). As depicted; the ketals 5and 6 were also found (by omr) to be related to each other as cis and trans isomers. Furthermore, each of them could be hydrolyzed with acid to the corresponding monobenzylidenes 2 and 3 without any isomerization. However, UV irradiation of compounds 2 and 3 gave equilibrium mixtures containing both the isomers, indicating isomerization had occurred under photolytic conditions.     

The Gem-Tetraziridinocyclotriphosphazene Diazide,A Synthon to Monophosphazenylmonoazido Derivatives of Biological Interest

Abstract

The gem-tetraziridinocyclotriphosphazenes, N₃P₃Az₄XY, are both antitumor agents (1, 2) and immuno-modulators (3, 4) whatever X and Y are, but their selectivity for malignant cells is commonly poor. In an attempt at the production of more selective drugs, we prepared monoazido derivatives (X=N₃, Y=something else) for covalent binding to antibodies.     

Isothiocyanatochloromethylphosphonates and Phosphinates – Versatile Synthones for Obtaining of S (Se), N,P–Containing Heterocycles

Abstract

Isothiocyanatochloromethyl(thio)phosphonates and (thio)-phosphinates 1 (X=O, S; R¹ = OPh, CH₂Cl, NCS; R² = H, Cl have been found to be convenient starting material for synthesis of a variety of S (Se), N, P-containing cyclic compounds. They react with different proton containing nucleophiles in the presence of a base with formation of saturated 2 and unsaturated 3 five membered phosphacyclanes. Diisothiocyanatodichloromethylphosphonates 1 (R¹ = NCS, R² =Cl) produce with amines and thiols appropriate bicyclic compounds 4.     

The Formation of Phosphacycloheptatrienes in Ring Enlargement Reaction

Abstract

The forrmation of substituted phosphacycloheptatrienes in ring expansion reaction(s) is describzd. From thc: reac-tion of 3,4-dimethyl-l-phenyl-3-phospholene-l-oxide(1,R¹ = c₆H₅, R₂=R₃ = CH₃) with dichlorocarbene under liquid-liquid phase transfer circumstances not the expected adduct but the appropriate phoshacycloheptatrisne (4, R_l, R₂,R₃ as above) was prepared. The formation of this product can be explained assuming two ring expansions effected by two series of dichlorocarbene addition and cyclopropane ring opening. In the similar reaction of the methoxy-phospholenc derivative (1, R¹=CH₃O, R² = R³ = CH3 four other products are also formed beside the phosphacyclohcptatriene. Again phosphacycloheptatrienes (4) are formed as the result of dichlorocarbene addition to the regioisoners of dihidrophosphorins (2) obtained from the phospholene-dichlorocarbene adducts by thermolysis. The same product can be derived from each regioisomeric pair.     

The Reaction of Diethanolamine with 2-Chloronitrobenzene-A Reinvestigation

In a report on the reaction of 2-chloronitrobenzene (1) with diethanolamine (2), Meltsner et al ¹ claim that the expected S_NAr product, N-(2-nitrophenyl)diethanolamine (3), is not formed; rather that the products are 2,2′-dichloroazobenzene (4), 2-nitrophenol (5), 2-chloroaniline (6) and 4-(2-aminophenyl)morpholine (7). Similar products in which the nitro function is reduced are also reported² for the corresponding reaction with ethanolamine. In this laboratory, in an attempted preparation of 2,2′-dichloroazobenzene (4) for reference purposes in photochemical studies on the antineoplastic agent 5-(3-azido-4-chlorophenyl)-6-ethyl-pyrimidin-2,4-diamine³, the expected S_NAr product (3) was obtained along with other products.     

Synthesis and Reactions of 2,3,4,6-Tetra-O-Acetyl-1-S-(N-Acylaminoacyl)-1-Thio-β-D-Glucopyranoses

Abstract

Fully acetylated 1-thio-β-D-glucopyranosyl esters of N-protected amino acids (4–13) were prepared in high yields by condensation of 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose (1) with a pentachlorophenyl esters of N-protected amino acids (2) in the presence of imidazole, or bN-protected amino acids (3) in the presence of DCC + imidazole. High tendency of the S-acyl aglycon group in 4–13 to undergo S → O and S → N migrations was demonstrated in reactions with several alcohols and amines.     

Synthesis of the Four Configurational Isomers of N-Benzoyl-2, 3, 6-Trtdeoxy-3-C-Methyl-3-Amino-L-Hexose from the (2S, 3R)-Diol Obtained from α-Methylcinnamaldehyde by Fermentation with Baker'S Yeast

Abstract

The erythro and threo chiral C₅ methyl ketones (4) and (5), prepared from the (2S, 3R)-methyl diel (1b), were converted into the phenylsulfenimines (6) and (7), which, in turn, on reaction with allyl-magnesiutn bromide, yielded after acid hydrolysis and benzoylation, the diastereoisomeric C₈-N-aminodiol derivatives (9) and (11), with threo stereochemistry relative to positions 4 and 5. Ozonolysis of (9) and (11) yielded the l-arabino and l-xylo 3-O-methyl branched aminodeoxysugar derivatives (13) and (15), respectively. Using diallylzinc as the reagent, the diastereoisomeric erythro products (8) and (10) were obtained. The latter materials gave the l-ribo-and l-lyxo-(lL-vancosamine) derivatives (12) and (14) upon oxonolysis. The ¹H and ¹³C NMR spectra of the four isomeric aminodeoxysugar derivatives (12)—(15) were discussed.     

Selective α-D-Galactosylation of Benzyl 4,6-O-Benzyhdene-β-D-Galacto-Pyranoside with 2,3,4,6-Tetra-O-Benzyl-α-D-Galactopyranosyl Bromide Under Catalysis by Halide Ion

Abstract

Selective glycosylation of benzyl 4,6-O-benzylidene-β-D-galacto-pyranoside (1) with 1.5 mole equivalent of 2,3,4,6-tetra-O-binzyl-α-D-galactopyranosyl bromide (2) catalyzed by halide ion gave the (1→2)-α-(5) and (l→3)-α-D-linked disaccharide (7) derivatives in 22 and 40% yields, respectively. The D-galactose unit at the reducing end of 2-O-α-D-galactopyranosyl-D-galactose [11) at equilibrium in D₂O was shown By ¹³C NMR spectroscopy to exist in the pyranose and furanose forms in the ratio of ～2:1.     

Phosphorus-Nitrogen Compounds: The Reactions of Hexachlorocyclotriphosphazatriene with Pentane-1,5-Diol. Nuclear Magnetic Resonance Studies of The Products

Abstract

From the reactions of hexachlorocyclotriphosphazatriene, N₃P₃Cl₆ (1) with pentane-1,5-diol (2) in dichloromethane solution, the following derivatives have been isolated: 2,2-spiro(1′,5′-pentanedioxy)-4,4,6,6-tetrachlorocyclotriphosphazatriene, N₃P₃Cl₄[O(CH₂)₅O] (3); its ansa isomer, 1,3-ansa(1′,5′-pentanedioxy)-1,3,5,5-tetrachlorocyclotriphosphazatriene, (4); bis spiro(1′,5′-pentanedioxy)-6,6-dichlorocyclotriphosphazatriene, N₃P₃Cl₂[O(CH₂)₅O]₂ (5); its spiro-ansa isomer, (1′,5′-pentanedioxy)-1,3-dichlorocyclotriphosphazatriene (6); as well as the bino(1,5-pentanedioxy)-di-(pentachlorocyclotriphosphazatriene), N₃P₃Cl₅ [O(CH₂)₅O]N₃P₃Cl₅ (7), and tri-bino(1,5-pentanedioxy)-di (trichlorocyclotriphosphazatriene), N₃P₃Cl₃[O(CH₂)₅O]₃N₃P₃Cl₃, (8) derivatives. Their structures were established by MS and NMR with the use of ¹H, ¹³C, and ³¹P spectroscopy. Product types and relative yields are compared with those of the previously investigated diol derivatives. The yield of the mono-ansa product (25%) obtained in this system was considerably increased relative to those of the propane-1,3-diol derivative (11.2%) and decreased relative to the 2,2-dimethyl-propane-1,3-diol (36.2%), and bis(2-hydroxyethyl) ether (34.5%) derivatives.     

Synthesis of 2-Carbamoyl-2-Deoxy Glycosides

Abstract

Recently we have reported the addition of trichloracetyl isocuyanate to glycals 1 _1,2,3. The reaction led to the highly stereoselective formation of a mixture of unstable [2+2] and [4+2] cycloadducts 2 and 3. The isocyanate adds to the glycal moiety anti to the substituent at C-3. The addition of benzylamine to the reac6tion mixture led to N-deprotection of 2 and allowed us to isolate stable bicyclic β-lactams 4 _1-3. We have shown also that 2 (a mixture of α-L-gluco and β-L-manno isomers) obtained from L-rhamnal 1 (R¹[dbnd]Ac, R²[dbnd]CH₃ under high pressure, when treated with methanol, underwent a rapid trans opening of the four-membered ring to give respective glycosides 5(β-L-gluco and α-L-manno isomers). On the other hand 3 (R¹[dbnd]Ac, R²[dbnd]CH₃) under the same conditions added a molecule of methanol to the C[dbnd]N double bond affording 6.     

Darstellung Der Isomeren 1,6-DI-O-Acetyl-3,4-Didesoxy-α, β-D-Glycero-Hex-3-Enopyrahos-2-Ulosen

Abstract

Prolonged treatment of tetra-O-acetyl-1, 5-anhydro-hex-1-enitols (“tetra-O-acetyl-hydroxy-glycals”) 3 and 5 with BF₃ in CH₂Cl₂ at RT lead to anomeric mixtures of the title compounds 2 and 4a, the α-anomer 4a dominating. Reaction of 5 gave the higher yields of 4a (71%) and 2 (12%), the results being accounted mechanistic grounds. The same reaction performed in an aromatic solvent, like toluene, gave rise to competing C-alkylation., The ortho and para-tolyl derivatives 6 and 7, also with enone structure, were isolated in a combined maximum yield of 40% from 5. β-Enone 2 was also prepared in moderate yield by thermolysis of β-d-glucopyranose pentaacetate (1). In this case no α-anomer 4a was detected.     

The reactions of cyclotriphosphazene with 2-(2-hydroxyethylamino)ethanol. Spectroscopic studies of the derived products

Abstract

The reactions of cyclotriphosphazene (1) with 2-(2-hydroxyethylamino)-ethanol (2) were investigated. 2-(2-hydroxyethylamino)-ethanol (2) is a tri-functional reagent consisting of both aliphatic hydroxyl and the secondary amino groups and its nucleophilic substitution reactions with cylotriphosphazene can lead to different product types; open chain, spiro, ansa, bridged and their mixtures. The reactions with one, two and three equimolar ratios of 2-(2-hydroxyethylamino)-ethanol, in the presence of NaH at 0–10?°C and at room temperature gave the following cyclotriphosphazene derivatives: one mono-spiro, N₃P₃Cl₄[O–(CH₂)₂–NH–(CH₂)₂–O] (3, 1:1, r.t.); its isomer mono-ansa (5, 1:1, r.t.); one dispiro, N₃P₃Cl₂[O–(CH₂)₂–NH–(CH₂)₂–O]₂ (4, 1:1, r.t.); its isomer spiro-ansa (6, 1:2, r.t.); and one single-bridged compound with spiro substituted units, N₃P₃Cl₃[O–(CH₂)₂–NH–(CH₂)₂–O]₃N₃P₃Cl₃ (7, 1:3, at 0–10?°C); as well as single-, N₃P₃Cl₅[O–(CH₂)₂–NH–(CH₂)₂–O]N₃P₃Cl₅ (8, 1:2, r.t.), double-, N₃P₃Cl₄[O–(CH₂)₂–NH–(CH₂)₂–O]₂N₃P₃Cl₄ (9, 1:2, r.t.), and tri-bridged, N₃P₃Cl₃[O–(CH₂)₂–NH–(CH₂)₂–O]₃N₃P₃Cl₃ (10, 1:3, at 0–10?°C) derivatives. Triple-bridged derivative is the major product in this system. The structures of the novel-derived compounds were characterized by TLC-MS, FT-IR, elemental analysis, ¹H, and ³¹P NMR spectral.     

Synthesis of N-Alkyl-N'-cyano-N″-4-pyridylguanidines from 4-Pyridyldithiocarbamic Acid via N-Alkyl-N′-4-Pyridylthioureas,or via 4-Pyridylcyaniminothiocarbamic Acid

Several years ago a number of antihypertensive N-alkyl-N′-cyano-N″-pyridylguanidines was prepared by addition of cyanamide to N-alkyl-N′-pyridylcarbodiimides which were obtained from the respective thioureas and phosgene or triphenylphosphine/carbon tetrachloride¹. Recently we have described some attractive synthetic methods for N-alkyl-N′-4-pyridylthioureas², based on 4-pyridyldithiocarbamic acid (1) (Scheme 1). We now report on the synthesis of N-alkyl-N′-cyano-N″-4-pyridylguanidines (4) from (1) by two different routes which ultimately may pass through a common intermediate (3) (Scheme 1).     

A Synthesis of 2-(6′-Carboxy-2′-cis-Hexenyl)-4-Hydroxycyclopent-2-EN-1-ONE,a Prostagiandin Intermediate1

Several recent publications² report the synthesis of prostaglandin E₁ (PGE₁, 2) and some of its derivatives by conjugate addition reactions to ether-ester forms of hydroxycyclopentenone acid 1.³ The simplicity of this approach makes its application to the preparation of prostaglandins of the PG₂- and PG₃ - series (cis-Δ⁵)⁴ an attractive alternative to the existing elegant methods.⁵ We now wish to report a five-step synthesis of the requisite hydroxycyclopentenone precursor 3 from the readily available⁶ lactone 4.