Phase transfer azides

A newer and equally effective way of swapping azides with halides (bromines or iodines) is in the use of phase transfer catalysts [68]. Strike wouldn t expect an underground chemist to purchase the exotic catalyst Aliquat 336 which the investigators in this reference used to get yields approaching 100% but an alternative catalyst of... 

Recently, a nice bee named Quirks submitted an article from our new, favorite patron researcher Rajender S. Varma. This time the good doctor is tackling our azide problem with another novel use of his clay phase transfer catalyst system. This is just going to be... 

Nucleophilic substitution by azide ion on an alkyl halide (Sections 8 1 8 13) Azide ion IS a very good nucleophile and reacts with primary and secondary alkyl halides to give alkyl azides Phase transfer cata lysts accelerate the rate of reaction... 

Far superior yields of l-(arylsulfonyl)-l//-azepines 16 are now available by a one-pot synthesis involving the action of sodium azide on an arylsulfonyl chloride under solid-liquid phase-transfer conditions which prevents the formation of acidic sulfonamides and, hence, the ring-contraction process.75 This procedure also has the advantage of avoiding the use of high pressures and the isolation and handling of the potentially explosive sulfonyl azides. 

Alkyl azides can be prepared by treatment of the appropriate halide with azide ion. ° Phase-transfer catalysis,ultrasound,and using reactive clays as a... 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

Phase transfer conditions are used as well for the preparation of azides.73... 

Tetrazolium salts have found use as phase transfer catalysts in the oxidation of benzaldehyde640 and toluene193 and the displacement reaction of acid chlorides with sodium azide.639... 

Reduction of azides is a classical approach to primary amine synthesis. Treatment of 17 with sodium azide in DMF or in THF/H2O mixtures in the presence of phase transfer catalysts effects a quantitative conversion to the corresponding polymeric azide, 27. Recently the reduction of azides to primary amines via hydrolysis of iminophosphoranes produced by interaction of the azide with triethyl phosphite was reported.30 Application of this technique to the azidomethyl polymer, 27, as shown below, failed to produce a soluble polyamine. 

Quaternary ammonium azides will displace halogens in a synthesis of alkyl azides. Dichloromethane has been used as a solvent, although this can slowly form diazido-methane which may be concentrated by distillation dining work-up, thereafter easily exploding [1]. An accident attributed to this cause is described, and acetonitrile recommended as a preferable solvent, supported polymeric azides, excess of which can be removed by filtration are also preferred in place of the tetrabutylam-monium salt [2]. A similar explosion was previously recorded when the quaternary azide was generated in situ from sodium azide and a phase transfer catalyst in a part aqueous system [3,4],... 

Substituted furo[3,2-3 4,5- ]dipyrroles 364 were prepared from the appropriate vinyl azides 363 under phase transfer catalyzed conditions (Scheme 76) <1994H(37)1695>. 

In order to construct the L-asparagine derivative of per-O-acetylated 0-(2-acetamido-2-deoxy-/ -D-glucopyranosyl( 1 — 4)-2-acetamido-2-deoxy-D-glucose (7), Spinola and Jeanloz (13) used (the sensitive) silver azide for conversion of the a-chloro anomer of the chitobiose derivative 8 into the / -azido derivative 9. Kunz and associates (14,15) have accomplished the conversion of the a-chloro anomer of 8 into 9 using sodium azide in the presence of tri-n-octyl-methylammonium chloride as a phase-transfer catalyst in chloroform water. 

All the above reactions of PVC were performed homogeneously in DA-solvents such as HMPA, DMF and dimethylsulfoxide (DMSO). For the practical modification of PVC, the reaction must be conducted under more commercial conditions as in slurry water. As mentioned before, azidation of PVC did not occur in water. However, the reaction proceeded feasibly in water by addition of some cationic surfactant to give, e.g. 8-20% (DS) of azidated PVC at 80°C by use of tetra-n-butyl ammonium chloride (1 ). The use of cationic surfactant was also effective in organic solvents and attracted increased attention as the conception of "phase transfer catalyst" in organic chemistry developed. 

The nucleophilic displacement of the halogen from 2,4-dinitrohalobenzenes by azide ion is catalysed by macrotricyclic ammonium salts [69], Kinetic studies indicate that the azide ion is entrapped and transported within the macrocyclic cage. The highly explosive tetra-azido-p-benzoquinone is obtained when the tetrachloro-quinone is reacted with an excess of sodium azide under phase-transfer catalytic conditions [70]. When only a twofold excess of the azide is used, the 2,5-diazido-3,6-dichloro compound is obtained. 

The synthesis of aryloxysulphonyl azides, which can be used as precursors for sulphamates, is improved by the use of tetra-n-butylammonium azide under homogeneous conditions in place of an alkali metal azide [ 1 ]. A stoichiometric amount of the ammonium azide is used and no attempts appear to have been made to conduct the reaction under solid liquid phase-transfer catalytic conditions. 

Arylamines and hydrazines react with tosyl azide under basic conditions to yield aryl azides [1] and arenes [2], respectively, by an aza-transfer process (Scheme 5.25). Traditionally, the reaction of anilines with tosyl azides requires strong bases, such as alkyl lithiums, but acceptable yields (>50%) have been obtained under liquidiliquid phase-transfer catalytic conditions. Not surprisingly, the best yields are obtained when the aryl ring is substituted by an electron-withdrawing substituent, and the yields for the corresponding reaction with aliphatic amines are generally poor (-20%). Comparison of the catalytic effect of various quaternary ammonium salts showed that tetra-/i-butylammonium bromide produces the best conversion, but differences between the various catalysts were minimal [ 1 ]. 

Although aliphatic azides can be prepared under liquidrliquid phase-transfer catalytic conditions [3-5], they are best obtained directly by the reaction of a haloalkane with sodium azide in the absence of a solvent [e.g. 6, 7]. Iodides and bromides react more readily than chlorides cyclohexyl halides tend to produce cyclohexene as a by-product. Acetonitrile and dichloromethane are the most frequently used solvents, but it should be noted that prolonged contact (>2 weeks) of the azide ion with dichloromethane can produce highly explosive products [8, 9] dibromomethane produces the explosive bisazidomethane in 60% yield after 16 days [8]. 

A single report of the addition of sodium azide to cyclohexene in the presence of iodine under phase-transfer catalytic conditions to produce 2-iodocyclohexanyl azide has the potential for extension to other alkenes [17], The analogous reaction of cyclohexene with potassium thiocyanate and iodine produces 2-iodocyclohexyl isothiocyanate (17%) and 2-iodocyclohexanyl thiocyanate (61%). Similar products are obtained with other alkenes [17],... 

The reaction of activated methylene groups with tosyl azide to yield the corresponding diazo derivatives proceeds in high yield [23]. The phase-transfer catalysed reaction is sensitive to the strength of base used the reaction of acetoacetic esters requires relatively mild conditions, otherwise diazoacetic esters are produced (Table 5.41). 

To facilitate accesses to suitably functionalized sialic acid derivatives and complex sialyloligosaccharides for other usehil neoglycoconjugates, phase transfer catalysis (PTC) has been exploited extensively [for reviews see 42]. This process provided a wide range of carbohydrate derivatives under essentially clean Sn2 transformations. In the case of acetochloroneuraminic acid 1, the PTC reactions always provided inverted a-sialic acid derivatives [43]. para-Formylphenyl sialoside 7 [44], together with many other sialoside derivatives such as 8-10 [43], including thioacetate 12 [45] and azide 14 [46], were thus obtained (Scheme 1). Aldehyde 7 and similar glycosides are of particular interest since they could be directly conjugated to protein by reductive amina-tion after suitable deprotection [44]. 

The synthesis of the amino alcohol (5S,6S)-6-amino-5-decanol begins with reaction of the 1-chloropentylboronic ester (Section 1.1.2.1.3.1.) with sodium azide under phase-transfer conditions to form the a-azido boronic ester, which yields the a-chloro- -azidoalkyl boronic ester (1) [yield 92 % 95 % de] with (dichloromethyl)lithium under the usual conditions. The reaction of 1 with butylmagnesium chloride is unusual in that it requires zinc chloride in order to accomplish the replacement of chlorine by butyl to form /J-azidoalkyl boronic ester 2 without boron-azide /1-elimination. Standard peroxidic deboronation and reduction of the azide complete the synthesis15. 

For the synthesis of amino acids, the reaction of an a-haloalkyl boronic ester 4 with sodium azide and a phase-transfer catalyst in dichloromethane/water requires a large excess of azide in order to form the a-azidoalkyl boronic ester 5 with only 1-2% epimer34. With the exception of R1 = benzyl, where epimerization of 4 is relatively rapid, bromoalkyl boronic esters are preferred. Chloroalkyl boronic esters react so slowly that the azide and dichloromethane may generate hazardously explosive diazidomethane65,66. Chain extension of 5 to 6 proceeds normally. Sodium chlorite, which is known to oxidize aldehydes to carboxylic acids67-69, also oxidizes a-chloroalkyl boronic esters to carboxylic acids34. The azido acid is hydrogenated to the amino acid. 

Alkyl azides can be prepared by treatment of the appropriate halide with azide ion.939 Phase transfer catalysis940 and ultrasound941 have been used. Other leaving groups have also been used,942 for example, OH,943 OMs, OTs,944 and OAc.945 Epoxides react with NaN3, with HN3 in DMF,94 or with HN3-Et3Al947 to give 3-azido alcohols these are easily converted to aziridines,948 e.g.,... 

Compounds containing a CH2 bonded to two Z groups (as defined on p. 464) can be converted to diazo compounds on treatment with tosyl azide in the presence of a base,164 The use of phase transfer catalysis increases the convenience of the method.165 p-Dodecylbenzenesul-fonyl azide,166 methanesulfonyl azide,167 and p-acetamidobenzenesulfonyl azide168 also give the reaction. The reaction, which is called the diazo transfer reaction, can also be applied to other reactive positions, e.g., the 5 position of cyclopentadiene.169 The mechanism is probably as follows ... 

Cyclic a-diazo ketonesDiazo transfer can be conducted under phase-transfer conditions (tetra-n-butylammonium bromide or 18-crown-6) wth this arylsulfonyl azide. Other arylsulfonyl azides (mesityl, tosyl) are unsatisfactory. The method may not offer significant advantages with simple ketones, but is the most satisfactory route to hindered diazo ketones. Isolated yields in five cases were 48-84%. 

AMIDES Bis(o-nitrophenyl)phenyl-phosphonate. N,N-Bis(2-oxo-3-oxazoli-dinyl)phosphordiainidic chloride. 2-Chloro-2-oxo-l,3,2-bcnzodioxa-ph05-phole. Iodine azide. N-Methyl-N-phenyl-benzohydrazonyl bromide. Phase-transfer catalysts. N-Phenylseleno-phthalimidc. (SEProlinol. 

Alkyl azides. Sodium azide as such is of little use for preparation of alkyl azides by nucleophilic substitution reactions because of solubility problems. The reaction can be carried out under phase-transfer conditions with methyltrioctylam-monium chloride/NaN3.3 An even more effective polymeric reagent can be obtained by reaction of NaN3 with Amberlite IR-400.4 This reagent converts alkyl bromides, iodides, or tosylates into azides at 20° in essentially quantitative yield. The solvents of choice are CH3CN, CHC13, ether, or DMF. 

In azide addition to quinones, the triazoline adducts are spontaneously oxidized to the triazoles.1-8 9,279-281,317,392 393 Potassium permanganate32,155,286,288 and nickel peroxide394 also effect triazoline oxidation. Permanganate oxidation of 1,5-substituted triazolines in a two-phase system using a phase-transfer catalyst provides a convenient route to the synthesis of 1,5-disubstituted triazoles (Scheme 118).395,396 Triazoline 4-carboxylic esters32,287,288 and a 4-carboxamide397 are converted to triazoles by potassium permanganate and nickel peroxide, respectively. 

RN3- RNH2 The reduction of azides to amines normally proceeds in poor yield, but can proceed in 79-92% yield if carried out with NaBH4 in toluene-water in the presence of hexadecyltributylphosphonium bromide as phase-transfer catalyst. 

Tropper, F Andersson, F., Braun, S., and Roy, R. (1992) Phase transfer catalysis as a general and stereoselective entry into glycosyl azides from glycosyl halides. Synthesis 618-620. 

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