2-benzopyrylium salts. XXXVII. Oxygen analogs of reissert compounds : molecular structure and reactions with sodium hydroxide

The weak intensity of the CN stretching band in IR spectra for 1-cyanoiso chromenes is obviously determined by the steric position of the CN group in the molecule, as it was established by X-ray structural analysis for the cyanide addition product 2d of 1-isopropyl-3-methyl-2-benzopyrylium salts. Depending on the other substituent in position 1, 1-cyanoisochromenes in aqueous solutions of sodium hydroxide eliminate hydrogen cyanide 2a, b, e, undergo inter-3a, b or intra-mlecular 2c, d recyclisation, or hydrolysis of the cyano group in 2f ; reaction products include α-naphthols 7c, e, β-naphthol 7d, acylchrysenes 5a, b, or the iso chromene-amide 11f , a stable 1-alkylideneisochromene 3e was obtained, and the intermediacy of 3-hydroxy-1-alkylideneiso chromenes was proved by their isolation in the cases of 10c, d     

Condensed heterotricycles: Pyrido(1,2,3- de )(1,4)benzoxazines, pyrido(1,2,3- ef )(1,5)benzoxazepines and pyrido(1,2,3- fg )(1,6) benzoxazocines

Cyclization of N-(2-haloacyl)-8-hydroxy-l,2,3,4-tetrahydroqumolines4–7 and9 with alkali affords pyridobenzoxazinones21–24 and26 respectively and of the 4-chlorobutyramide13 with NaH, the benzoxazocinone31. Exposure of 3-chloropropionamide12 to NaH affords acrylamide15, benzoxazepinone28 or methyl benzoxazinone22 or mixtures thereof under various conditions.28 undergoes rapid base-catalysed ring contraction to22. NaH-catalysed ring closure of acrylamide15 affords mixtures of22 and28, while from the crotonamides16 and17, the methylbenzoxazepinones29 and30 are obtained preponderantly, the former amide yielding only traces of the ethyl benzoxazinone23.29 shows no propensity for ring contraction to give23. The cinnamoyl derivatives18,19 and20 are cyclized to benzyl benzoxazinones24,27 and25, respectively. The intermediacy of the phenyl benzoxazepinone39 in the formation of24 has been established by deuteration studies. Benzylidene benzoxazinone41 is obtained from dibromocinnamamide14 and propiolamide40. Dichloracetamides8 and10 undergo interesting ring closure to compounds45–54 upon treatment with amines. The course of electrophilic reactions of the lactams depends upon the ring size. Contribution No. 18 from Searle R & D Centre Presented at a symposium to felicitate Prof N S Narasimhan at the University of Poona, November 18–19, 1988     

Saturated heterocycles 115: Cycloaddition of nitrilimine and nitrile oxide to norbornane- and norbornene-fused dihydro-1,3-oxazines

By cycloaddition of nitrilimine and nitrile oxide to diexo and diendo norbornane- and norbornene-fused structural isomeric dihydro-1,3-oxazlnes (1-3), tetracyclic 1,3-oxazino-1, 2,4-trlazolines (7-9) and 1,2,4-oxadiazolines (10-12) were obtained. With norbornehe dipolarophiles, which contain a C=N and a C=C bond, the cycloaddition takes place at the olefinic bond and the diexo compound 4 yields 13 regioselectively, whereas the diendo isomer 5 gives an Isomeric mixture of isoxazolines 14 and 15. From the diexo derivative 6, however, a bis-adduct 16 is formed. The stereostructures of the adducts have been elucidated by NMR spectroscopy.     

Determination of stereostructure of naturally occurring α, β-unsaturated δ-lactone derivatives through a stereoselective synthesis

The stereostructures of (Z)-tarchonanthuslactone (2) and the δ-lactone of (Z)-5, 7, 9, 11-tetrahydroxyhexacos-2-enoic acid (3) were established as9 and27 by the stereoselective syntheses of authentic9 and26 (triacetate of3), respectively.     

Peptide ozonolysis: Product structures and relative reactivities for oxidation of tyrosine and histidine residues

Angiotensin II (DRVYIHPF) and two analogs, (DRVYIAPA and DRVAIHPA), were used as model systems to study the ozonolysis of peptides containing tyrosine and histidine residues. The ESI mass spectrum of angiotensin II following exposure to ozone showed the formation of adducts containing one, three, and four oxygen atoms. CID and SID spectra of these adducts were consistent with formation of Tyr+O and His+3O as expected from previous work with amino acids. However, several fragment ions observed in the CID and SID spectra suggested formation of a rather unexpected adduct, Tyr+3O, and a small amount of the Phe+O adduct. These findings were confirmed by examining two angiotensin analogs. Exposure of DRVYIAPA to ozone resulted in the addition of either one or three oxygen atoms on Tyr, while DRVAIHPA showed only the addition of three oxygen atoms—all on His. Other noteworthy minor oxidation products were observed from these analogs including Tyr+34 Da, His+5 Da, His+34 Da, and His+82 Da. The reaction rates of the peptides with ozone were found to be similar: second-order rate coefficients are 274 ± 3, 379 ± 6, and 439 ± 34 M⁻¹s⁻¹ for DRVYIAPA, DRVAIHPA, and angiotensin II, respectively. The relative rates indicate (1) an isolated His residue has a slightly greater ozone reactivity than an isolated Tyr residue, and (2) the reaction rates of isolated residues are not additive when both residues are present in the same molecule.     

Flavonoids, 40.+ Synthesis of 3-alkyl- and -arylthioflavanones and their transformations into sulfur-containing flavonoids

trans-3-Mesyloxyflavanones 1 were converted into cis- and trans-3-(alkylthio)- and -(phenylthio) flavanones 2-4 by nucleophilic substitution reaction with thiols or thiolates. Flavanones 2-4 were useful intermediates in the synthesis of various sulfur-containing derivatives; flavanones, flavones and dihydrochalcones possessing alkyl- or arylthio, -sulfinyl and -sulfonyl group. Oxidation of cis- and trans- isomers of 4 led to completely different products.     

New synthesis of steroidal tetrahydrooxazin-2-ones

In the DMSO/NaHCO₃ system, 16α-aminomethyl-, 16α-benzylaminomethyl- and substituted benzylaminomethyl-3-methoxy-17β-tosyloxyestra-1,3, 5(10)-triene (3, 5a-k) do not undergo oxidation, but form a tetrahydrooxa-zin-2-one ring (7, 8a-k) via neighboring group participation. Under similar conditions, 16β-aminomethyl-3-methoxy-17β-tosylestra-1,3,5(10)-triene (4) decomposes into 16-methylene-3-methoxyestra-l,3,5(10)-trien-17-one (12).     

Synthesis of 3-methyl-coumarins, -thiacoumarins and -carbostyrils

Reaction of 3,6-dimethyl-4-phenyl-3,4-dihydrocoumarin5a with anhydrous aluminum chloride gave 3,6-dimethyl-coumarin (6a); likewise, 6-chloro-3-methyl-coumarin (6b) was obtained from5b. Substituted 3-methyl-thiacoumarins (8a,b and 3-methyl-carbostyrils (10a-e) were prepared from the reactions of the respectivea-methyl-cinnamoyl derivatives (7a,b and (9a-e), of thiophenols and anilines.     

Duryne,a new cytotoxic agent from the marine sponge Cribrochalinadura

Duryne, 1, a cytotoxic metabolite which inhibits the growth of both mouse and human tumor cell lines invitro has been isolated from the marine sponge Cribrochalinadura. Its structure has been assigned by spectral methods.     

Are all charge-repulsed carbocations really unstable? Dramatic difference in reactivities of benzyl- and p -methoxybenzyl halides in benzene

Two distinct reaction mechanisms are proposed for the reactions of1,5 and6 with nucleophiles as against those of11,12 and16. The former set undergoes the reactions through carbocation type intermediates2 and3 as efficiently as the stable carbocation4 does, even under similar and very mild conditions. The compounds from the latter group do not form the carbocations under the same conditions and undergo only direct substitution by strong nucleophiles.     

Synthesis of trans -N-2-aryl(heteryl)ethenamidines

2-Amino-2-arylethylamides1 carrying electron-donating substituents in thepara position are transformed by hot POC1₃ to the the title compounds2, presumably via iminochlorides 7 and imidazolium derivatives8. Amides lacking this para-substituent give rise to chloroamidines11 under these conditions.m-Methoxyphenethylamide1t and POCl₃ form, besides11f, an isoquinoline derivative3. The involvement of an imidazolium compound8 in the formation of ethenamidines has been verified by the synthesis of2a from10. Reaction of amide1w with PCl₅ in the cold leads to, besides the chloroamidine11c, thecis-ethenamidine12 which equilibrates with thetrans-isomer2o in hot toluene. Thienylethyl urea13 converted by hot POCl₃ to the imidazoline16, while phenylpropylamide17 forms only the iminochloride18a. Contribution No. 752 from Research Centre     

Saturated heterocycles—113: Synthesis and stereochemical investigation of cis- and trans-1-substituted 7,8-dimethoxy-1,4,5,9b-tetrahydro-2H-azeto[2,1-a]isoquinolines

Stereospecific and stereoselective syntheses starting from 1-[bis(hydroxymethyl)methyl)]- (1) and 1-ethoxycarbonyl-methylene-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (13) gave cis- and trans-1-chloromethyl- (10, 4a), 1-methyl- (11, 12) and 1-benzyl-1,4,5,9b-tetrahydro-2A-azeto(2,1-a]iso-quinolines (20, 21). The steric structures of the diastereomers were determined'By NMR spectroscopy.     

Polyene cyclization : cyclization studies on an acyclic furanoditerpene and its epoxide

Reaction of an acyclic diterpene alcohol 1c with chlorotrimethylsilane and sodium iodide or SnCl₄ furnishes compounds 7 and 8. This cyclization is reminiscent of the biosynthesis of pallescensins E-G - an analogous compounds in sesquiterpenoids. Reaction of the epoxide 2 with SnCl₄ furnishes only the acyclic compounds 12, 13, 14a, 14 c and 15a. Photolysis of 2 results in the formation of (4+2) photocycloaduct 21.     

Anomalous1H NMR spectra of 3,4-dihydroisoquinolines and related compounds

Solutions of 3,4-dihydro-6,7-methylenedioxyisoquinoline (1) and analogues2–5 and9 as well as isoquinolines7 and8 in certain samples of CDCl₃, CCl₄, DMSO-d₆ or acetone-d₆ gave rise to anomalous¹Hnmr spectra with extreme line broadening, signals due to protons at C-l and C-3 most often not being seen. The spectra of1 and3 were most striking in this respect.¹Hnmr spectra of the quaternary salt10 and the model schiff base11 were normal. Several hypotheses for the observed line broadening have been considered and rejected, a slow equilibrium1 ⇆13 being one of them. NaBH₄ reduction of1 and2 followed by mass spectrometric analysis of the crude tetrahydroisoquinolines16 and17 ruled out a slow equilibrium1 ⇆14 and2 ⇆15 as contributory cause for line broadening. The crude reduction products unexpectedly contained N-ethyl species22 and25. Their formation is rationalised     

Synthesis of N-substituted acrylamides

Summary The following compounds have been obtained and characterized for the first time:O-,m-, andp-ethoxyphenyl-acrylamides and N -methyl-o-, -m- and -p-N-ethoxphenylacrylamides.     

Regioselective hydroborations of methylvinylchlorosilanes

The regioselectivity of the hydroboration of the methylchlorovinylsilanes, Cl_nMe_3?nSiCHCH₂ (n= 0 ? 3), has been investigated using BH₃←THF, 9-BBN, disiamyl- and dicyclohexylborane. Methylation of the adducts with methylmagnesium bromide is complicated by formation of tetraalkylboronates. Alkaline hydrogen peroxide oxidation of the boronates gives reasonable yields of the corresponding α- and β-trimethylsilylethanols forn= 0 and 1. Forn= 2 and 3, conversion of the adducts to the corresponding α- and β- deuteroethylsilanes by treatment with excess sodium methoxide in methanol-0-d provides a more effective means of derivatization. Addition of the alkenes,n= 2 or 3, to excess BH₃←THF givesca. 90% of the α-boro-organo-chlorosilanes. For all of the alkenes, the dialkylboranes giveca. 80% of the β-boron adducts.     

A sixfold triplet-sensitized Z/E isomerization of a π-perimeter macrocycle

On irradiation, all-Z [2.2.2.2.2.2]orthoparacyclophene (1) is converted to the all-E isomer (2). The photo-isomerization occurs via the triplet state and proceeds without any groun state intermediates.     

Surprising reactions or special azoolefins - self-arylation,indole ring closure,mild chlorine substitution,and “tert. amino effect”

Azoolefins 2 either decompose or react with aryldiiminea with uptake of an aryl group to give compounds 3. The latter can undergo ring closure to N-amino-indoles 4. In the 2,4,6-trichloro compound 3bortho-chlorines are selectively replaced bymorpholine under very mild conditions giving 5a, which easily fragments to form the benzimidazole 7.     

Synthesis of ζ -pyrromycinone, 7-deoxyauramycinone,and 7-deoxyaklavinone via ketoester cyclizatiON 1)

7,10-O-Dimethyl- ζ -pyrromycinone (78) and the not naturally occurring 7-deoxyanthracyclinones 76 and 77 are prepared via base itinduced cyclization of the ketoesters 73 - 75, and stereoselectively hydroxylated to the 2,4-cis diol 83 and 85.