Sandmeyer Reaction Research Articles

Structure verification of some chlorinated p-cymenes by high field NMR and IR spectroscopies

Seven chlorinated p-cymenes were synthesized by the chlorination of p-cymene and the alkylation of chlorinated toluenes. 2,6-Dichloro-p-cymene was made by the Sandmeyer reaction from 2-amino-6-chloro-p-cymene and 2,3,5-trichloro-p-cymene was synthesized by the chlorination from 3,5-dichloro-p-cymene. The chlorinated compounds were purified by preparative gas chromatography. The coupled 13C NMR spectra of (1) p-cymene, (2) 2-chloro-, (4) 2,3-dichloro-, (8) 2,3,6-trichloro-, and (10) 2,3,5,6-tetrachloro-p-cymenes were recorded by a high field NMR spectrometer and the IR spectra of nine chlorinated p-cymenes were recorded.

Zur Synthese von Benzoesäurederivaten aus 3‐Ethoxymethylen‐2,4‐alkandionen und Malonsäuredinitril

Synthesis of Benzoic Acid Derivatives from 3‐Ethoxymethylene‐2,4‐alkanediones and MalononitrileReaction of the 3‐ethoxymethylene‐2,4‐alkanediones 1a–c with malononitrile (2) gives the benzonitrile derivatives 3a–c. Compounds 4a–d are obtained by acid or basic hydrolysis of the nitrile group of 3a–c, Sandmeyer reaction leads to the halogenated benzonitriles 5a–f. Compounds 6a, b are available from 3a and O‐ethyl‐ and O‐allylhydroxylamine hydrochloride.

ChemInform Abstract: Palladium‐Catalyzed Coupling of 2‐Bromoanilines with Vinylstannanes. A Regiocontrolled Synthesis of Substituted Indoles.

AbstractThe o‐bromoanilines (IV), prepared by convenient methods such as Sandmeyer reaction and reduction of nitrobenzenes, are N‐tosylated and then treated with the vinylstannane (VII) in the presence of a Pd(0) catalyst, yielding the 2‐vinyl‐N‐tosylanilines (VIII).

Axially Dissymmetric Bis(triaryl)phosphines in the Biphenyl series: Synthesis of (6,6′‐dimethylbiphenyl‐2,2′‐diyl)bis(diphenylphosphine) (‘BIPHEMP’) and analogues, and their use in Rh(I)‐catalyzed asymmetric isomerizations of N,N‐diethylnerylamine

AbstractThe axially dissymmetric diphosphines (−)‐(R)‐ and (+)‐(S)‐(6‐6′‐dimethylbiphenyl‐2,2′‐diyl)bis(diphenyl‐phosphine) ((−)‐(R)‐10 and (+)‐(S)‐10; ‘BIPHEMP’) have been synthesized, starting from (R)‐ and (S)‐6,6′‐dimethylbiphenyl‐2,2′‐diamine ((R)‐ and(S)‐16), respectively, via Sandmeyer reaction, liathiation, and phosphinylation. Moreover, racemic 4,4′‐ dimethyl‐ and 4,4′‐bis(dimethylamino)‐substituted analogues 11 and 12 respectively, and the 6,6′‐bridged analogues 1,11‐bis(diphenylphosphino)‐5,7‐dihydrodibenz[c,e]oxepin (13) were synthesized and resolved into optically pure (R)‐ and(S)‐enantiomers via complexation with di‐μ‐chlorob is {(R)‐2‐[1‐(dimethylamino)ethyl]pheny‐CN}dipalladium(II) ((R)‐18). The molecular structures of the diphosphines (S)‐10 and (R)‐13 and of two derived cationic Rh(I) complexes,[Rh((S)‐ 10)(nbd)]BF4 and [Rh((R)‐ 13)(nbd)]BF4 were determined by x‐ray analyses. Absolute configurations were established for (+)‐(S)‐ 10 by X‐ray analyses of both the free diphosphine and of the derived Rh(I) complex, and for (−)‐(R)‐ 13 by X‐ray analysis of the derived Rh(I) complex. Configurational assignments for the substituted BIPHEMP analogues 11 12 were achieved by means of 1H‐NMR comparisons. The BIPHEMP ligand 10 and analogues 11, 12 and 13 are the first examples of optically active bis(triaylphosphines) containing the axially dissymmetric biphenyl moiety. All these new diphosphines proved to be excellent asymmetry‐inducing ligands in Rh(I)‐catalyzed isomerizations of N,N‐diethylnerylamine affording citronellat enamine of 98‐99% ee.

Synthesis of 2,3-dihydro-1,4-benzodioxin derivatives. I. 2-substituted-5(and 6)-sulfamoyl-2,3-dihydro-1,4-benzodioxins.

In order to study new sulfonamide diuretics, two series of 6- and 5-sulfamoyl-2, 3-dihydro-1, 4-benzodioxins were synthesized and tested for diuretic and antihypertensive activities in rats. Starting from 4-chloro(or 3, 4-dichloro)-1, 2-dihydroxybenzene, these sulfamoyl compounds were prepared by two different routes. In method A, 6-sulfamoyl compounds (8 or 11) were obtained by conversion of the nitro function into sulfonamide via the Sandmeyer reaction. In method B, 5-sulfamoyl compounds (16) were synthesized by direct introduction of sulfonyl chloride into the dihydrobenzodioxin, followed by amination. The sulfamoyl dihydrobenzodioxins showed lower diuretic and antihypertensive activities than trichloromethiazide.

The isomerisation of some 2,4-dihalogen benzene diazonium compounds

In this study the isomerisation of some 2,4-dihaIogeno benzenediazonium compounds was investigated and the isomerisation products were obtained. The halogenoanilines containing chlorine, bromine and iodine in their 2- and 4- positions were used as substrates. The diazctisa- tion reactions were carried out in concentrated sulphuric acid. The nucleophiles used in Sandmeyer reaction were chloride, bromide and iodide. During the isomerisation reactions the chlorine and bromine in 4- position were found to give 1—2 and 1—3 shifts respectively. The structures of the products obtained were elucidate with their physical constants and with spectroscopic methods.

ChemInform Abstract: Synthetic Approach to Diterpene Alkaloids. Part 2. Unusual Reaction of Angular Nitromethyl Group with Diazomethane to Give Aldoxime.

AbstractThe nitromethylhydrophenanthrone (I) is converted via nitration, hydrogenation and Sandmeyer reaction into the phenol (IV), which reacts with diazomethane to give the desired methyl ether (V), together with two unexpected isomeric aldoximes (VIa) and (VIb).

The synthesis of some 2,4‐disubstituted derivatives of quinolone‐3‐carboxylic acids and carbonitriles

AbstractIn order to prepare the 2‐chloro derivative of oxolinic acid, ethyl 1‐ethyl‐1,4‐dihydro‐2‐hydroxy‐6,7‐methylenedioxy‐4‐oxo‐3‐quinolinecarboxylate was treated with phosphorus oxychloride. The compound obtained was the 4‐chloro‐2‐oxo‐quinoline. The structure was confirmed by 13C nmr and mass spectral techniques. The 2‐halocarbonitrile was obtained by a Sandmeyer reaction but could not be hydrolysed into the acid.

ChemInform Abstract: The Synthesis of 3‐Hydroxymethyldibenzo(b,f)thiepin 5,5‐Dioxide, a Prostaglandin Antagonist.

AbstractThe aniline (Ia) undergoes Sandmeyer reaction, yielding the halobenzene derivatives (Ib) and (Ic), which are treated with thiophenol (II) to yield the diaryl sulfide (Id).

ChemInform Abstract: Synthesis and Mass Spectra of 2‐Amino‐ and 2‐Chloro‐5‐aryl‐1,3,4‐thiadiazoles.

AbstractThe cyclization of the thiosemicarbazones (III) with ferric chloride leads to the formation of the 2‐aminothiadiazoles (IV) which are transformed into the 2‐chlorothiadiazoles (V) by the Sandmeyer reaction.

フェナントロールの置換反応 ＸＩＩＩ ９‐フェナントロールの臭素化

9-Phenanthrol had been known to give the 10-substituted compounds on the electro-philic substitutions. In this paper the second site of bromination of[1]was established as follows. Dibromo-9-phenanthrol, obtained by bromination of[1]in CS2, was converted to bromo-9-phenanthrol[4]by reduction with Zn/AcOH.[4]was converted to dibromophenanthrene[6]by Bucherer's reaction followed by a modified Sandmeyer's reaction as shown in Scheme (1). Compound[6]was identified as 3, .6-dibromophenanthrene by comparison with an authentic specimen obtained from 9-bromo-3-phenanthrol. Accor-dingly, the second bromination of[1]is revealed to occur at the 3-position.

A convenient s rn1 synthesis of aromatic nitriles from diazonium salts [formula omitted] diazosulfides

Properly substituted diazosulfides XC 6H 4-N=N-SPh ( 1 ) (either isolated or generated in situ from arenediazonium tetrafluoroborates and sodium benzenethiolate) react with tetrabutylammonium cyanide, in Me 2SO under photon or electron stimulation, leading to nitriles XC 6H 4CN ( 2 ). Satisfactory yields of 2 , comparable with those of the Sandmeyer reaction, are obtained when X = 3- or 4-CF 3 , 2-, 3-, or 4-CN, 4-F, 4-MeO, 3-MeCO, 4-NO 2, 4-PhCO, and 4-PhSO 2. For different reasons, the reaction practically fails as a useful nitrile synthesis when X = H, 4-MeO, 2-, or 3-NO 2. The collected evidences agree well with the intervention of an S RN1 mechanism, to which diazosulfides 1 , given their easy reduciblity followed by a prompt fragmentation of the C-N and N-S bonds, are convenient participating substrates. An important consequence of the mechanism involved is the behaviour of bromo and chloro derivatives ( 1 : X = Br, Cl) which lead, through the contemporaneous introduction of two cyano functionalities, to more than satisfactory yields of the corresponding dicyanobenzenes.

Synthesis and mass-spectrometric study of 2-amino- and 2-chloro-5-aryl-1,3,4-thiadiazoles

The cyclization of aldehyde thiosemicarbazones with ferric chloride yielded 2-amino-5-aryl-1,3,4-thiadiazoles, forming 2-chloro-5-aryl-1,3,4-thiadiazoles in the Sandmeyer reaction. The mass-spectrometric behavior of the 2-amino- and 2-chloro-5-aryl-1,3,4-thiadiazoles was studied; the typical routes of fragmentation characteristic of each group of compounds were found.

ChemInform Abstract: Synthesis of 3‐Amino‐2‐cyanocarbazole and 3,4‐Dihydro‐4‐oxo‐6H‐pyrimidino‐[5,4‐b]carbazoles.

AbstractAus dem Aminonitrocarbazol (I) wird nach Sandmeyer das Nitril (II) hergestellt.

The chemistry of indoles. XXIV. Syntheses of 3-indoleacetic acid and 3-indoleacetonitrile having a halogeno group and a carbon functional group at the 4-position.

Various 4-halogeno-3-indoleacetic acids and -3-indoleacetonitriles were synthesized for the first time by means of the Sandmeyer or Schiemann reaction, demonstrating the versatility of 4-indolediazonium salts in 4-substituted indole chemistry. A practical synthetic method for 4-halogenoindoles was developed by regio-selective thallation-halogenation, and the products were also led to 4-halogeno-3-indoleacetic acids. The first synthesis of 4-formyl-3-indoleacetonitrile is also reported.

Synthesis of 3-amino-2-cyanocarbazole and 3,4-dihydro-4-oxo-6H-pyrimidino(5,4-b)carbazoles.

The application of the Sandmeyer reaction to 2-amino-3-nitrocarbazole (1) gave 2-cyano-3-nitrocarbazole (5), which could be reduced to 3-amino-2 cyanocarbazole (6), 3-amino-2-carbamoylcarbazole (8) or 3-amino-2-methylcarbazole (9) according to the reaction conditions used. Intramolecular cyclization of the carbazoles (6), (7) and (8) afforded 3, 4-dihydro-4-oxo-6H-pyrimidino [5, 4-b] carbazoles (11), (12) and (13). 4-Amino-6H-pyrimidino [5, 4-b] carbazole (14) was obtained by cyclization of 3-amino-2-cyano-carbazole (6) with formamide. Treatment of 3-amino-2-carbamoylcarbazole (8) with carbonyl chloride gave 1, 2, 3, 4-tetrahydro-2, 4-dioxo-6H-pyrimidino-[5, 4-b] carbazole (15). The proton nuclear magnetic resonance spectra of the products were studied.

Synthesis of 14C‐anthralin

Abstract1,8‐dihydroxy‐[10‐14C]9‐anthrone (anthralin) was synthesized in good yield starting from readily available 3‐methoxy‐2‐(2‐methoxybenzyl)‐benzoic acid (3).14C was introduced via carboxylation of the Grignard derived from 3‐bromo‐2(2‐methoxybenzyl) anisole. This, in turn, was obtained from (3) by a Curtius and Sandmeyer reaction sequence.

Pyridonecarboxylic acids as antibacterial agents. 2. Synthesis and structure-activity relationships of 1,6,7-trisubstituted 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids, including enoxacin, a new antibacterial agent.

The title compounds having nitro, amino, cyano, chloro, or fluoro as the C-6 substituent were prepared. Introduction of the chloro and cyano groups at C-6 was accomplished by the Sandmeyer reaction of 6-amino-1,8-naphthyridine derivatives 9 via their 6-diazonium salts. The reaction was extended to the synthesis of the 6-fluoro analogues, involving the Balz-Schiemann reaction of the diazonium tetrafluoroborate. Furthermore, a series of the 1-ethyl, 1-vinyl, 1-(2-fluoroethyl), and 1-(difluoromethyl) analogues of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids was prepared. 1-Pyrrolidinyl and, particularly, N-substituted or unsubstituted 1-piperazinyl groups were introduced as the C-7 variants. As a result of this study, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1, 8-naphthyridine-3-carboxylic acid (named enoxacin, originally AT-2266) was found to show the most broad and potent in vitro antibacterial activity, an excellent in vivo efficacy on systemic infections, and a weak acute toxicity. Structure-activity relationships of compounds with variations of substituents at C-1, C-6, and C-7 are also discussed.

Substituent effects on the Sandmeyer reaction. Quantitative evidence for rate-determining electron transfer

The substituent effect in the Sandmeyer reaction of aromatic diazonium salts induced by several reducing cations (Sn2+, Cu+, Fe2+) has been determined in H2O–dioxane (2:1). Electron-withdrawing substituents increase the reactivity of the substrate in the radical chlorodediazoniation process, while the reverse holds for electron donor ones. For the change of the reduction potential of the reductant from 0.15 to 0.77 V the Hammett ρ value varies from 0.6 to 1.0. Conventional spectrophotometry has been employed to measure the rate of the reaction of two diazonium ions with Fe2+: reasonable agreement is found with the rate constants for the corresponding electron transfer step as calculated according to Marcus theory. The conclusion is drawn that the electron transfer step is rate determining in the Sandmeyer reaction under these conditions.

Angiotensin‐II Analogues. I: Synthesis and incorporation of the halogenated amino acids 3‐(4′‐iodophenyl)alanine, 3‐(3′,5′‐dibromo‐4′‐chlorophenyl)alanine, 3‐(3′,4′,5′‐tribromophenyl)alanine, and 3‐(2′,3′,4′,5′,6′‐pentabromophenyl)alanine

AbstractThe synthesis of the polyhalogenated phenylalanines Phe(3′,4′,5′‐Br3) (3), Phe(3′,5′‐Br2‐4′‐Cl) (4) and DL‐Phe (2′,3′,4′,5′,6′‐Br5) (9) is described. The trihalogenated phenylalanines 3 and 4 are obtained stereospecifically from Phe(4′‐NH2) by electrophilic bromination followed by Sandmeyer reaction. The most hydrophobic amino acid 9 is synthesized from pentabromobenzyl bromide and a glycine analogue by phase‐transfer catalysis. With the amino acids 4, 9, Phe(4′‐I) and D‐Phe, analogues of [1‐sarcosin]angiotensin II ([Sar1]AT) are produced for structure‐activity studies and tritium incorporation. The diastereomeric pentabromo peptides L‐ and D‐13 are separated by HPLC. and identified by catalytic dehalogenation and comparison to [Sar1]AT (10) and [Sar1, D‐Phe8]AT (14).