Synthetic method

Several methods can be employed for the synthesis of polyether-6-amide copolymers. Though thermal polymerization is probably the most important one, the synthesis can also be carried out in solution or via an interfacial technique. Sometimes a combination of two methods may be required. The polymerization can also be carried out in one or two steps, and in one or two pots. Each method has its advantages and drawbacks, and the choice of the method will usually depend on the nature of the starting material. 

Synthetic Methods.—The preparation of phosphate esters by 5n2 attack of phosphate ester anions on carbon is receiving more attention following the realization that the poor nucleophilicity commonly associated with such anions is due to solvation and ion-pairing effects. Thus tetra-methylammonium di-t-butyl phosphate reacts with primary and secondary alkyl iodides in aprotic solvents to give the corresponding triesters (1) from which the t-butyl groups are readily removed by trifluoracetic acid. The proposal of a similar S 2 mechanism in the reaction of triphenylphosphine and ethyl azodicarboxylate with a phosphate diester in the presence of an 

Phosphorylation procedures using activated phosphate esters continue to be developed and esters of the type (3) may be conveniently prepared from monoalkyl phosphates and imidazole (or 2-hydroxypyridine) using bis-(2-pyridyl) disulphide and triphenylphosphine. -Nitrophenyl phosphate (4) and its symmetrical pyrophosphate (5) have been found to phosphorylate alcohols in the presence of pyridine and it is probable that 

Preparative studies have been reported on the phosphorylation of a series of hydrazines and hydrazones and on the phosphorylation of vicinal diamines with diphenyl phosphorochloridate. The cyclic phosphoramidate esters (12) and (13) may be obtained by treatment of the appropriate acyclic 

Diethyl trichloromethylphosphonate (16) reacts with ribonucleotides, and presumably with other vicinal 1,2-diols, in the presence of triethyl-amine to give a mixture of the 2 - and 3 -phosphates. The readily available ct-hydroxyphosphonate esters (17) rearrange in base to the phosphate 

The synthetic methods described in SRI s 1991 patent applications [ 1,2] are based principally on the idea of nitrating nitramine to obtain the dinitramide. The nitration agents are various nitronium salts, such as NO2BF4. 

The dinitraminic acid is converted in a subsequent step by a cation exchange with a salt MX, where X could, for example, be a halide. 

In principle, this route can also be described as nitration of ammonia, since nitramine can be obtained by nitration of ammonia with nitronium salts. 

In the same patents is reported a method described as P-elimination of l-(N,N-dinitramino)-2-trimethylsilylethane catalyzed by cesium fluoride. After recrystallization in ethyl acetate, the yield was 50% 

The SRI researchers later introduced an approach whereby ammonium nitrourethane can be nitrated with N2O5 or NO2BF4 to give dinitrourethane. In a subsequent step, the urethane is cleaved with ammonia resulting in ADN. This route has been used in the US in scaled-up 

The synthetic methods that are in general use for the preparations of linear polyesters can be summarized as follows  

The above transesterification reaction is practical for use with high melting and poorly soluble dicarboxylic acids. In addition, less energy is needed to remove alcohol than water. 

in place of dicarboxylic acid chlorides, phosgene is used, polycarbonates form  

Many modifications of the above reactions are known. For instance, poly(propylene phthalate) can be prepared from phthalic anhydride and propylene oxide. The reaction is catalyzed by tertiary amines that probably form carboxylate ion intermediates  

This produces a low molecular weight polyester. A modification is a reaction of a dianhydride with a glycol  

One of the most common synthetic approach to 1,2,3-, 1,2,4- and 1,3,5-triazines, bearing fluorine atoms as substituents in the ring, consists of the nucleophilic displacement of chlorine or bromine atoms with the fluoride anion in the 

In principle, several general methods are available for the synthesis of polyboranes and their derivatives, and only three will be discussed in more detail  

Preparation of hydridopolyborates followed by subsequent protonation or substitution reactions (cluster expansion). 

A survey of the literature has revealed that many of the various methods reported for the preparation of metal nanopartides are applicable to a number of metals across the Periodic Table. For example, salt reduction using main group hydride-reducing agents has been used for the preparation of many metals in nanosized form (not only those cited in this subchapter). It is not the goal here to provide a directory of all reports of nanopartides syntheses, but rather to provide examples of the principal types of preparative methods that can be used. 

The synthetic methods used have induded modem versions of established methods of metal colloid preparation, such as the mild chemical reduction of solutions of transition metal salts and complexes. Some of these reactions have 

In this sense, structures such as spheres, cubes, rods, hollow cages, and wires are attracting ever-more interest indeed, the creation of these structures frequently requires the use of special conditions, a situation which will be discussed by means of examples in the following sections. 

Hydro complexes of nickel, palladium, and platinum have been synthesized by several methods employing acidic, basic, and neutral media. The preparative procedures discussed in the following sections do not represent the complete range of methods available for the synthesis of these complexes nevertheless, they do include many of the more widely applicable methods and show the diversity of the chemistry involved. 

Reduction with Metallohydrides Such as Borohydride and Aluminum Hydride 

The complex PtHCl(PEt3)2 has been prepared by reacting PtCl2(PEt3)2 with LiAlHi (78). Sodium borohydride can be used to prepare the 

Treatment of /ra s-hydrochlorobis(tricyclohexylphosphine)nickel(II) with sodium borohydride in a mixed solvent (acetone and ethanol) under argon yields tra r-hydroborohydrobis(tricyclohexylphosphine)nickel(II), which has been shown to have the pentacoordinate structure (III) (769). 

This complex itself acts as a hydridic reducing agent and, in benzene, reacts with MX2(PR3)2 (M = Ni or Pd) to form new hydro complexes  

The following three preparations, adapted from the literature, demonstrate the primary methods of synthesis of benzo and naphthopyrans. 

To a 500-ml reaction flask were added, l,l-diphenyl-2-propyn-l-ol (0.1 mol, 20.8 g, Farchan Laboratories), 2-naphthol (0.11 mol, 15 g) and 200 ml of toluene. The mixture was warmed to 55°C with stirring while dodecylbenzenesulfonic acid was added dropwise until a permanent dark red-black color was obtained. The temperature was maintained at 55°C until thin-layer chromatography (TLC) indicated the reaction was complete (approximately 1 h). Then the mixture was poured into an equal volume of 10% aqueous sodium hydroxide, shaken, and the organic fraction separated. The toluene solution was washed with water, phase separated, and the solvent removed on a rotary evaporator. The resulting light tan crystals were slurried with hexane, suction filtered, and dried to yield 18.4 g of product with a melting point range of 156-158°C. 

Under an atmosphere of dry nitrogen, titanium tetraethoxide (2.4 g, 10.4 mmol) in 10 ml of dry toluene was added over 10 min to 2-methyl-6-hydroxybenzothiazole (1.72 g, 10.4 mmol) in 40 ml of dry toluene. When the addition was complete, the reaction mixture was boiled for 15 min and then slowly distilled to remove the ethanol. A total of 20 ml of solvent was collected. The reaction mixture was allowed to cool to room temperature and P-phenylcinna-maldehyde (2.17 g, 10.4 mmol) in 50 ml of dry toluene was added dropwise to it. When the addition was complete, the reaction mixture was refluxed for 2 to 5 h, allowed to cool, and poured onto 100 ml of dilute aqueous ammonium chloride solution. The organic layer was separated, dried over anhydrous magnesium sulfate, and the solvent removed on a rotary evaporator. The residue was chromatographed on silica using 40% diethyl ether in pentane as eluent. The photochromic fractions were combined, the solvent removed, and the crystalline residue recrystallized from a heptane-benzene mixture. The product (1.6 g, 44%) had a melting point of 215°C. 

Dean-Stark trap. During this period the yellow reaction mixture turned first crimson and then dark brown. Toluene was removed under reduced pressure and the residual enamine crystallized from acetone as discolored crystals (8 g). The enamine (10 g) was treated with concentrated HC1 (1 ml) in methanol (200 ml). The crimson solution was evaporated and the residual dark oil crystallized from acetone, yielding the intermediate ketopyran (8.4 g, yellow needles from acetone). The crystals were added to methanol and an excess of sodium borohydride was gradually added to the solution, yielding on standard workup 7.47 g of the hydroxypyran. The crystalline hydroxy intermediate was well mixed with 4.5 g of anhydrous copper sulfate and heated to 150-160°C in a carbon dioxide current for 10 min. Upon cooling, the product was extracted into methylene chloride. Removal of the solvent under reduced pressure gave 6.3 g of discolored solid that was decolorized with carbon and recrystallized from acetone (melting point not reported). 

Five major synthetic routes are now available for the preparation of metallocarboranes, although only one was well established in 1969. The recently developed synthetic methods have allowed the preparation of more complex and diverse compounds and have greatly expanded the field of metallocarborane chemistry. These preparative methods are discussed in some detail in this section, for the synthesis of all the known metallocarboranes have been accomplished by one or more of these routes. 

As mentioned previously, the first metallocarborane synthesized, (l,2-C2B9Hu)2Fe(II)2- (Fig. 3), was prepared in a manner similar to the synthesis of ferrocene, e.g., reaction of anhydrous FeCl2 with the nido-carborane dianion 7, S-C BgHn2, which itself was formed from 1,2-C2BioHi2 

The reaction conditions for this type of preparation generally involve nonaqueous solvents, such as tetrahydrofuran (THF) or diethyl ether, and rigorous exclusion of air and water. Some metallocarboranes, however, may be prepared in high yield by reaction of a metal salt and the nido monoanion, C2B9H12-, in strong aqueous base  

In these instances, it is believed that the strong base deprotonates the monoanion to a small extent, permitting complexation to occur. 

This synthetic approach proved valuable for the preparation of lower monometallocarboranes as well the C2B7Hn2 ion, prepared from 6,8-C2B7H13, was found to react with metal ions, losing one equivalent of hydrogen gas, to form metallocarboranes of the type (C2B7H9)2Mn 4 (88). 

R1 = Alkyl or aryl group R2 = Alkyl group R3 = H or alkyl group 

As already discussed (Section 2.2.1.3), interchange reactions are also implicated in the formation of random copolyesters exhibiting the most probable molar mass distribution when polyester blends are melt mixed. They are also involved in the randomization of block copolyesters taking place in the melt upon heating.2,m 211 

Although low-molar-mass aliphatic polyesters and unsaturated polyesters can be synthesized without added catalyst (see Sections 2.4.1.1.1 and 2.4.2.1), the presence of a catalyst is generally required for the preparation of high-molar-mass polyesters. Strong acids are very efficient polyesterification catalysts but also catalyze a number of side reactions at elevated temperature ( 160°C), leading to polymers of inferior quality. Acid catalysts are, therefore, not much used. An exception is the bulk synthesis of hyperbranched polyesters reported in Section 2.4.5.1, which is carried out at moderate temperature (140°C) under vacuum in the presence of p-toluene sulfonic acid catalyst. The use of strongly acidic oil-soluble catalysts has also been reported for the low-temperature synthesis of polyester oligomers in water-in-oil emulsions.216 

Since anhydrides are much more reactive than carboxylic acids, reaction kinetics is controlled by the second step. The scope and apphcations of this reaction are the same as direct polyesterification but are practically limited to the synthesis of unsaturated polyesters and alkyd resins from phtliahc and maleic anhydrides (see Sections 2.4.2.1 and 2.4.23). 

The standard procedure for the synthesis of leuco dyes related to benzoyl leuco Methylene Blue is straightforward. The one-pot synthesis is carried out in a two-phase water-toluene system. Methylene Blue is first dissolved in the aqueous phase and reduced with sodium dithionite under nitrogen and with stirring. The yellowish leuco is extracted into the organic phase where it is allowed to react with an acid chloride, the aqueous phase being made alkaline. 

Leuco Azure A or B is obtained by refluxing the dye in an acid anhydride in the presence of zinc powder wherein the dye is reduced and acylated at the same time. 

Synthetic Method 1 6-(dimethylamino)-3-(N-acetyl-N-methylamino)-10-acetylphenothiazine 8a (procedure from US. Patent 4,652,643).5 A mixture of 9.0g of 6-(dimethylamino)-3-(methylamino)phenothiazin-5-ium chloride (Azure B), 150.0ml of acetic anhydride, and lO.Og of zinc dust was maintained at reflux temperature for approximately 4 hs. After the reaction mixture was cooled to ambient temperature, it was poured into ice water with stirring and 300ml of toluene was added. After stirring for approximately 30 min the toluene layer was separated and washed twice, once with tap water and once with saturated aqueous sodium chloride solution. The toluene was then distilled off at reduced pressure. The residue which remained was dissolved in ethyl acetate and separated into various components by subjecting the solution to column chromatography using silica gel as substrate. Elution with ethyl acetate yielded a white-colored solid. 

Methylene Violet, which is a well-known phenothiazinone dye, is also reduced and acylated in one step by refluxing with zinc powder in an acid anhydride. 

Reduction of Methylene Violet with zinc in acetic acid gives the air-sensitive leuco 20 which is further reacted with acetic anhydride in mild conditions to yield the acetylated leuco 21. The latter being air stable can be isolated and, the ring N-H being less reactive is not affected by acetylation at room temperature. The leuco 21 is again aroylated to produce the leuco 22. Selective hydrolysis provides the desired leuco dye 12 which regenerates the true Methylene Violet (6) on oxidation.83 

Double Bond Systems Containing a Silicon Atom 

Silicon-Oxygen Double Bond Compounds (Silanones) 

In the previous reviews,1 la,d f syntheses of many examples of transient silicon-oxygen double bond compounds such as MeHSi=0, Me2Si=0, H2Si=0 (2), (H0)HSi=0 (silanoic acid), and (H0)2Si=0 (silicic acid) have been described, and they are reportedly isolated as stable species in the low temperature matrices. However, the stabilization of this extremely reactive double bond species is very difficult, and no stable example of silanone (RR/Si=0) has been isolated until now even by the methods of thermodynamic or kinetic stabilization. 

On the other hand, Driess et al. have succeeded in the synthesis and isolation of a stable silicon-arsenic double bond compound (13), the first stable arsasi-lene (arsanilidenesilane),19 and they found that the arsasilene 13 undergoes ready 

Since the silanone intermediates have been postulated as key intermediates in reports on the synthesis and reactions of organosilicon compounds,27 the isolation of a stable silanone and its characterization should be one of the most fascinating subjects in the future chemistry of low-coordinate organosilicon compounds. 

The characterized borabenzene metal compounds are listed in Table V. In this section the various entries into borabenzene-metal chemistry are described Sections VI and VII treat the reactions of these compounds. 

The reaction of cobaltocene with organoboron dihalides RBX2 (R = Me, Ph and X = Cl, Br mainly) and boron trihalides (BC13, BBr3) leads essentially to three types of (boratabenzene) cobalt complexes, 19,20, and 21 (7,57). CoCp2 plays a dual role in part it acts as a reductant, in part it 

The boranediyl insertion with BC13 and BBr3 gives products with 1-haloboratabenzene ligands which easily undergo nucleophilic substitution at boron complex 6 has been made in this way (57,79). However, these reactions have never been published in detail. 

Alkali metal boratabenzenes have a wide synthetic applicability just like alkali metal cyclopentadienides. Two syntheses have been developed Ashe s synthesis via organotin intermediates (23) and our cyanide degradation of bis (boratabenzene) cobalt complexes (61). 

The acidity of 30 has been measured with reference to Streitwieser s acidity scale (87) a pKA value of 15.8 for 30 as compared to 22.8 for fluorene and 18.5 for 9-phenylfluorene demonstrates a significant increase in acidity (87). 

A problem in these couplings is the identity of the end groups of the formed polymers. Pd-catalyzed dehalogenation and/or phosphonium salt formation are side reactions that are difficult to avoid. A concern for the structural integrity of the backbone is the formation of butadiyne defects. While there is no direct measure to determine the amount of butadiyne defects in PAEs, the numbers are estimated to range from 1 to 10% of all repeat units. 

Wilson JN, Windscheif PM, Evans U, Myrick ML, Bunz UHF (2002) Macromolecules 35 8681-8683. 

Breen CA, Deng T, Breiner T, Thomas EL, Swager TM (2003) J Am Chem Soc 125 9942-9943. P Pizzoferrato R, Berliocchi M, DiCarlo A, Lugli P, Venanzi M, Micozzi A, Ricci A, LoSterzo C (2003) Macromolecules 36 2215-2223. 

Many of the high Tc ceramic superconductors can be prepared by similar solid state techniques. In the Bi-Sr-Ca-Cu-O system Bi2Os, SrCOs, CaCOs or Ca(OH)2, and CuO are often used 

The volatility of the reactants is a concern in some solid state syntheses. This may be a slight problem in bismuth cuprates synthesized at high temperatures because Bi2Os has an appreciable vapor pressure at these temperatures (i.e. 900-950°C) however, chemical analyses of samples of bismuth-based superconductors before and after reactions at temperatures up to 900°C indicate no detectable loss of bismuth. This problem is much more severe in the case of thallium chemistry. 

The primary difficulty in preparing the thallium-based cuprate superconductors lies in the toxicity and volatility of the reactant Tl2Os and its decomposition products. Above 600°C, the following redox-vaporization process is well under way and would lead to substantial loss of reactant in an open system, although the 

The following sections will outline specific methods for the synthesis of Bi- and Tl-based cuprate superconductors. Because the synthetic methods and historical evolution of the compounds are different, the bismuth and thallium families are described separately. 

The level of base remaining is easily assessed on a qualitative level by 19F NMR spectroscopy. Pure, base-free B(C6F5)3 exhibits three sharp multiplets for the ortho, para and meta F atoms in C6D6. The chemical shift of the para F is particularly sensitive to the presence of any Lewis base in the system, shifting upfield by —10 ppm upon complexation. This resonance is thus visibly broadened even in the presence of 5-10% of THF or water and provides a convenient qualitative assessment of the level of basic impurities. 

Lewis Base Adducts of B(C6F5)3 and Related Compounds 

Due to its thermal and protic stability, B(C6F5)3 forms stable, isolable adducts with many Lewis bases [Eq. (4)], including weak Lewis bases often activated by Lewis acids for selective organic transformations. Because of the high LA strength of the borane, 

Adducts ofB(C6F5)3 that have been studied in detail either in solution or the solid state are collected in Table I along with selected solution NMR spectroscopic data and metrical parameters. In particular, both the nB NMR chemical shift35 and the separation between the resonances for the meta and para fluorine atoms in the 19F NMR spectrum109 are quite sensitive to the environment about the boron center and the strength of the LB-B(C6F5)3 interaction. Indeed, as shown in Fig. 1, a rough empirical correlation between these two NMR parameters is observed. Anomalies arise for two classes of LB more linear bases like nitriles or isonitriles that do not pyramidalize the boron center as severely and the RM1 adducts (M = Al, Ga). 

Details of syntheses of methadone and its congeners prior to 1960 are available in Janssen s extensive compilation of chemical and pharmacological data on diphenylpropylamine analgesics. 26) 

A veritable host of methadone-related structures has been investigated and the resultant structure-activity data are conveniently discussed (with some inevitable overlap) under the subdivisions of changes in (1) the basic gfoup, (2) the NCCCPh2 chain, (3) the oxygen function, and (4) the aromatic groups. 

Variation of the basic group of methadone has led to the morpholino (11a, phenadoxone, Heptalgin) and piperidino (lib, dipipanone, Pipadone) 

Variants of the ethyl ketone function of methadone, an aspect already broached with mention of dextromoramide, include ester, sulphone, and secondary alcohol functions in addition to (-amides. The ethyl ester analog 14a obtained by treating the acid chloride derived from methadone cyanide with ethanol is markedly inferior in potency to methadone, while the sulfone 14b (obtained by aminoalkylation of benzhydryl ethyl sulfone) is equipotent 

LAH reduces all three ketones and gives only one of the two possible diastereoisomeric alcohols designated the a-racemate in the cases of the branched chain ketones. The branched ketones give a//3 mixtures after treatment with sodium propanol from which the major (/3) isomer may be isolated. Similar results follow reduction of antipodal forms of methadone and isomethadone.(38) Both racemic methadols are inferior in potency to methadone (a, 0.08 yS, 0.2 methadone, 1) in the MHP test, but activity is more than restored on O-acetylation (a-acetate, 1.3 13-2). Racemic a-acety- 

The synthesis of organic substances containing isotopic carbon suffers from several limitations. The short half-life of C necessitates 

Furthermore, many condensations occur in moderate or low yields so that it is frequently necessary to spend a considerable amount of time and effort to carry out what might seem to be relatively simple s3mtheses. In Figs. 1 and 2 are listed most of the syntheses of this type that have been reported. A few deserve particular mention. 

Long has prepared oxalic acid in 50% yield by introducing C 02 into an evacuated flask containing molten potassium and sand. Acetic acid labelled with C in both carbons has been prepared by Barker and 

Kamen from NajC O by a bacterial synthesis. A total of 81 % of the was recovered in the acetic acid. Sakami, Evans and Gurin have prepared ethyl acetoacetate labelled with C in the carbonyl and carboxyl groups preparations of acetoacetate containing C located solely in the carboxyl or carbonyl group were also reported. 

C 300C,H, -k CH,.C 0-CH,-C 00CiH5 BrMgCHs C OOCiHs + CH, COOCHj - CHa CO CHjCnOOCsH, BrMgCHa COOC.H, + CHs C OOCH, - CH.-C OGHjCOOCaH, 

Another, and seemingly very powerful, reagent is the cyclic mixed anhydride (la), which is very readily opened by attack at phosphorus by alcohols or phenols even in the absence of base. The anion (lb), from dealkylation of (la) with a tertiary amine, is also an active phosphorylating agent for alcohols. Since the residual ketol group is easily removed, these compounds may prove to be useful additions to existing reagents. 

AW -Diphenylphosphorodiamidic chloride has been recommended as a convenient phosphorylating reagent for the preparation of nucleoside 3 -phosphates since it is stable, it gives very high yields, and the resulting esters 

Full details of the synthesis of unsymmetrical diesters of pyrophosphoric acid by the reaction of the disilver salt of a monoester of phosphorothioic acid and a phosphate monoester have been published. In view of the good yields, the mild conditions, and the absence of symmetrical pyrophosphate byproducts it appears to be superior to previous routes to the nucleotide pyrophosphate coenzymes. Further, the findings that the procedure is insensitive to 

The 9-fluorenylmethyl group (6) has been suggested as a useful addition to 

The readily available OO-dialkyl phosphorodithioic acids (13) are converted into the corresponding phosphorothioic acids by reaction with nitriles in the presence of limited amounts of waterX In view of the initial difficulty encountered in preparing the sulphur analogue, the simple synthesis of the selenopyrophosphate ester (14) from selenious acid and the cyclic phosphonate (15) is remarkableX  

From Carbonyl Compounds, Acids, Lactones, Anhydrides, and Related Compounds 

The standard synthesis of pyridazines from y-keto acids or esters has been applied to the preparation of many derivatives.  

Pyridazine syntheses from unsaturated 1,4-diketones have been applied in several new ways. ° The reaction with hydrazines is usually performed in the presence of mineral acid otherwise JV-aminopyrroles may be formed. Some saturated 1,4-diketones are claimed to react with hydrazines to give pyridazines. Instead of 1,4-dicarbonyl compounds, 

4-enaminoketones were employed. So far, this synthetic approach is limited to the preparation of 3,5-diaryl-4(lH)-pyridazinones (1). In the 

5-dione. The cis-isomer reacted readily to give 3,5-dimethylpyridazine, whereas the trans-isomer gave the same pyridazine in lower yield accompanied by about the same amount of three other compounds, one identified as 4-hydroxy-4-methyl-2-pentanone.  

Karklina, Biol. Aki. Savienojumu Kim. Technol. Rigas Polilech. Inst. 1, 86 (1974). 

Yurovskaya, and Nguyen Min Thao, Khim. Geterotsikl. Soedin., 1512 (1975). 

The disadvantage of this method, especially for large-scale work, hes in the utilization of large quantities of pyridine. Furthermore, with ethyl alcohol some ethyl phosphorodichloridate (II) is usually produced even under conditions favourable to the production of diethyl phosphorochloridate. 

Here again the disadvantage was the pyridine requirement in equation (a). The more readily accessible dimethylaniline can be used in place of pyridine in reaction (a), thus efifecting a considerable economy for large-scale work. We found also that the production of a faint yellow coloration, due to a slight excess of chlorine, is probably a better indication of the end-point of the reaction (b) than is the determination of the increase in weight of the reactants. 

A stiU more economical method for large-scale work was then sought, since a further drawback of methods (i) and (iii) is that 

We found that diethyl hydrogen phosphite (almost certainly as the tautomeric diethyl phosphonate (IV)), reacted very nadily with chlorine to give the required diethyl phosphoro-ohloridate (V) in 87 per cent yield  

The diethyl phosphorochloridate was characterized by the aiystalline diethyl phenylphosphoramidate (VI) formed by the action of anihne. 

Most of the important syntheses of cellulosic graft polymers involve irradiation with high-energy beams. Ultraviolet and x-ray sources are sometimes used, but Co radiation is used most often (Chapiro, 1962). In an oversimplified manner, the synthesis can be described as follows (Chapiro, 1962, p. 600)  

Rcell- + nM graft copolymer where M represents monomer II, and R cell—H represents cellulose. 

In the case of 1-deazapurine, syntheses were performed by liquid-assisted grinding of 1 1 mixtures of 1-deazapurine and coformer, in the presence of small volume of acetone. All forms were identified using PXRD and fourier transform infrared spectroscopy (FTIR) and compared to the patterns simulated from single-crystal diffraction data. Eight new forms were obtained by grinding, six of which were characterized by SC-XRD. 

This paper served as a sample study for the latter work with the supramolecular stabilization of Schiff base tautomers, where it was shown that these postulates can be successfully applied even to monocomponent molecular solids [67]. The Schiffbase X, synthesized by the condensation of 2-amino-3-hydroxypyridine and 

The structure of the other polymorph of X-ap was not determined by XRD, but and solid-state NMR data indicated that the same tautomeric forms were present in both polymorphs. The pure Schiff bases were synthesized from solution due to the sensitivity of imino bond to the water that is released during the aldehyde-amine condensation. Milling proved as a beneficial method for synthesis of multicomponent X-ap polymorphs, with much better yield and selectivity compared to solvosynthetic approaches. 

All four solid forms were structurally characterized, three of them by single crystal XRD and one keto-amino polymorph by high-resolution PXRD. It has been shown that each tautomer had a unique and specific geometry and primary synthons stabilizing its crystal structures. Keto tautomers have a similar geometry to that of X, with the oxygen atoms in cis position. As already discussed, the O-H- - -O synthon between OH(py) and oxo acceptor in keto tautomers 

While the proper crystallization conditions seem crucial for the formation of a specific solid tautomer of IX, the authors anticipate that control, not only of the tautomeric form, but also of potential solid-state tautomeric interconversions could be affected through careful selection of donor/acceptor functionalities of the peripheral groups, which can now be broadened to include a careful selection of a coformer molecule. 

---

Theilheimer, Synthetic Methods of Organic Chemistry, Volumes I-VIII, 1947-1954 (S. Karger, Basel). 

The most important pericyclic reaction in synthesis, indeed one of the most important of all synthetic methods, is the Diels-Alder reaction. We have seen this many times before. What are the clues for a Diels-Alder disconnection ... 

The synthetic methods illustrated in this chapter can be represented schematically as follows (compare Ref. 10) ... 

Comprehensive Catbanion Chemistry, edited by E. Buncel and T. Durst New Synthetic Method< ogy and Biologically Active Substances, edited by Z.-I. Yoshida... 

Acetoxylchlorination of norbornene (138) proceeds with skeletal rearrangement in the presence of an excess of CuCl2 to give e.Yo-2-chloro-iyn-7-acetoxy-norbornane (139). This is a good synthetic method for ivn-7-norbornenol[163]. 

The intramolecular reaction oF allcenes with various O and N functional groups offers useful synthetic methods for heterocycles[13,14,166]. The reaction of unsaturated carboxylic acids affords lactones by either exo- or endo-cyclization depending on the positions of the double bond. The reaction of sodium salts of the 3-alkenoic acid 143 and 4-alkenoic acid 144 with Li2PdCl4 affords mostly five-membcrcd lactones in 30-40% yields[167]. Both 5-hexe-noic acid (145) and 4-hexenoic acid (146) are converted to five- or six-mem-bered lactones depending on the solvents and bases[168]. Conjugated 2,4-pentadienoic acid (147) is cyclized with Li2PdCl4 to give 2-pyrone (148) in water[i69]. 

The carbonylation of alkene in AcOH-acetic anhydride in the presence of NaCl affords the /9-acetoxycarboxylic anhydride 242 in good yields and the method offers a good synthetic method for / -hydroxycarboxylic acid 243[222],... 

An intramolecular version offers useful synthetic methods for heterocycles. The total syntheses of a- and 7-lycoranes (373 and 374) have been carried out by applying the intramolecular aminochlorination of the carbamate of 5-(2-aminoethyl)-l,3-cyclohexadiene (372) as a key reaction[312,313]. Interestingly, the 4,6- and 5,7-diene amides 375 and 377 undergo the intramolecular amina-tion twice via x-allylpalladium to form alkaloid skeletons ofpyrrolizidine (376) and indolizidine (378), showing that amide group is reactive[314]. 

The reaction of iodobenzene with acrylate is a good synthetic method for the cinnamate 17[7]. In the competitive reaction of acrylate with a mixture of 0-and /i-iodoanisoles (18 and 19), the o-methoxycinnamate 20 was obtained selectively owing to the molecular recognition by interlamellar montmorillonite ethylsilyldiphenylphosphine (L) as a heterogenized homogeneous catalyst used as a ligand[28]. 

When allylic alcohols are used as an alkene component in the reaction with aryl halides, elimination of /3-hydrogen takes place from the oxygen-bearing carbon, and aldehydes or ketones are obtained, rather than y-arylated allylic alcohoIs[87,88]. The reaction of allyl alcohol with bromobenzene affords dihydrocinnamaldehyde. The reaction of methallyl alcohol (96) with aryl halides is a good synthetic method for dihydro-2-methylcinnamaldehyde (97). 

The intramolecular version for synthesizing cyclic and polycyclic compounds offers a powerful synthetic method for naturally occurring macrocyclic and polycyclic compounds, and novel total syntheses of many naturally occurring complex molecules have been achieved by synthetic designs based on this methodology. Cyclization by the coupling of an enone and alkenyl iodide has been applied to the synthesis of a model compound of l6-membered car-bomycin B 162 in 55% yield. A stoichiometric amount of the catalyst was used because the reaction was carried out under high dilution conditions[132]. 

Alkynes with EWGs are poor substrates for the coupling with halides. Therefore, instead of the inactive propynoate, triethyl orthopropynoate (350) is used for the coupling with aryl halides to prepare the arylpropynoate 351. The coupling product 353 of 3,3-dicthoxy-l-propyne (352) with an aryl halide is the precursor of an alkynal[260]. The coupling of ethoxy) tributylstan-nyl)acetylene (354) with aryl halides is a good synthetic method for the aryl-acetate 355[261]. 

The alkynyl iodide 359 undergoes cross-coupling with a terminal alkyne to give the 1,3-diyne 360[264]. No homocoupling product is formed. This reaction offers a good synthetic method for unsymmetrical 1,3-diynes. 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Another important reaction via transmetallation is carbon-metal bond formation by reaction with bimetallic reagents. This is a useful synthetic method for various main group organometallic reagents. 

Intramolecular allylation offers a useful synthetic method for macrocyclic compounds. An application to the synthesis of humulene (83) by the cycliza-... 

Regioselective 1,4-azidohydroxylation to give 309 takes place by the reaction of the vinyloxirane 308 with sodium azide[188]. The reaction of the cyclopen-tadiene monoepoxide 310 with sodium azide or purine base offers a good synthetic method for the carbocyclic nucleoside 311(189-191]... 

Cycloaddition involving the Pd-catalyzed trimethylenemethane (TMM) fragment 63 and the 1.3-diene 61 with an EWG offers a good synthetic method for the hydroazulene skeleton 65. The cydoaddition of trimethylene-... 

An interesting synthetic method for the [3.3.3]propellane 74 by intramolecular cycloaddition of a disubstituted methylenecyclopropane with an iinsa-... 

This reactivity pattern underlies a group of important synthetic methods in which an a-substituent is displaced by a nucleophile by an elimination-addition mechanism. Even substituents which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

Best Synthetic Methods is now 10 years old, is a family of 16 volumes and has been well received by the majority of chemists as a valuable aid in their synthetic endeavours, be they academic or commercial. The focus of the series so far has been on special methods, reagents or techniques. This volume is the first of a new sub-series with a focus on heterocycles and their synthesis. It is amazing the extent to which each heterocyclic type has its own specialized synthetic methodology. Whether the chemist is endeavouring to make a heterocycle by ring synthesis or wishes to introduce specific substituents, it is the intention that this new development will serve their needs in a practical, authoritative, fully illustrative and compact manner. Richard Sundberg is an authority on indole chemistry and it is a pleasure to have such a noted heterocyclist to initiate this venture. 

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

The Schiff base obtained is converted in good yield (60 to 80%) to amines by the action of Raney Ni (209). This reductive condensation provides a good synthetic method and was used to prepare thiazole analogs (62) of folic acid (Scheme 43) (210). These Schiff bases under... 

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