Phthalimides alcohols

Phthalimides. Alcohols are activated by (Me2N=CHCl) CF toward displacement with potassium phthalimide. By this method the synthesis of chiral amines from secondary alcohols (inversion of configuration) is accessible. 

Benzylatnine. Warm an alcoholic suspension of 118-5 g. of finely-powdered benzyl phthalimide with 25 g. of 100 per cent, hydrazine hydrate (CAUTION corrosive liquid) a white, gelatinous precipitate is produced rapidly. Decompose the latter (when its formation appears complete) by heating with excess of hydrochloric acid on a steam bath. Collect the phthalyl hydrazide which separates by suction filtration, and wash it with a little water. Concentrate the filtrate by distillation to remove alcohol, cool, filter from the small amount of precipitated phthalyl hydrazide, render alkaline with excess of sodium hydroxide solution, and extract the liberated benzylamine with ether. Dry the ethereal solution with potassium hydroxide pellets, remove the solvent (compare Fig. //, 13, 4) on a water bath and finally distil the residue. Collect the benzylamine at 185-187° the 3ueld is 50 g. 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Imides (e.g. phthalimide) can be purified by conversion to their potassium salts by reaction in ethanol with ethanolic potassium hydroxide. Hie imides are regenerated when the salts are hydrolysed with dilute acid. Like amides, imides readily crystallise from alcohols and, in some cases (e.g. quinolinic imide), from glacial acetic acid. 

Phosphine(s), chirality of, 314 Phosphite, DNA synthesis and, 1115 oxidation of, 1116 Phospholipid, 1066-1067 classification of, 1066 Phosphopantetheine, coenzyme A from. 817 structure of, 1127 Phosphoramidite, DNA synthesis and, 1115 Phosphoranc, 720 Phosphoric acid, pKa of, 51 Phosphoric acid anhydride, 1127 Phosphorus, hybridization of, 20 Phosphorus oxychloride, alcohol dehydration with. 620-622 Phosphorus tribromide, reaction with alcohols. 344. 618 Photochemical reaction, 1181 Photolithography, 505-506 resists for, 505-506 Photon, 419 energy- of. 420 Photosynthesis, 973-974 Phthalic acid, structure of, 753 Phthalimide, Gabriel amine synthesis and, 929... 

Potassium hydroxide, alcoholic, 7, 77 Potassium iodide, 4, 37 7, 14, 58 Potassium permanganate, 7, 18 8, 68 Potassium Phthalimide, 7, 8, 78 Potassium sulfate, 6, 2 Prest-o-lite tank, 8, 10 Propane-1, 1, 2, 3-Tetracarboxyuc Ester (Ethyl), 4, 29, 77 m-Propylbenzene, 4, 59 t 50-Propyl chloride, 5, 28 i-Propy] chloride, 5, 28... 

BromoaUylamine has been prepared by heating N-(2-bromo-allyl)-phthalimide with hydrazine in methanol 1 by treatment of 2,3-dibromopropylamine hydrochloride with excess alcoholic potassium hydroxide 6 by treatment of 1,2,3-tribromopropane with alcoholic ammonia at 100° and by the present procedure.7... 

Dissolve 0 6 g. of the primary amine and 0-6 g. of pure phthalic anhydride in 6 ml. of glacial acetic acid and reflux for 20-30 minutes. (If the amine salt is used, add 1 g. of sodium acetate.) The N-substituted phthalimide separates out on cooling. RecrystaUise it from alcohol or from glacial acetic acid. 

The modified procedure involves refluxing the N-substituted phthalimide in alcohol with an equivalent quantity of hydrazine hydrate, followed by removal of the alcohol and heating the residue with hydrochloric acid on a steam bath the phthalyl hydtazide produced is filtered off, leaving the amine hydrochloride in solution. The Gabriel synthesis has beai employed in the preparation of a wide variety of amino compounds, including aliphatic amines and amino acids it provides an unequivocal synthesis of a pure primary amine. 

Various electrophilic selenium reagents such as those described in Scheme 4.3 can be used. V-Phenylselenylphthalimide is an excellent reagent for this process and permits the formation of large ring lactones." The advantage of the reagent in this particular application is the low nucleophilicity of phthalimide, which does not compete with the remote internal nucleophile. The reaction of phenylselenenyl chloride or V-phenylselenenylphthalimide with unsaturated alcohols leads to formation of (3-phenylselenenyl ethers. 

Bromo-l-phthalimidopentane 3 was obtained in 72-82 g yield by refluxing 92 g of 1,4-dibromopentane 1, 55.5 g of potassium phthalimide 2, and 200 mL dry acetone on a steam bath for 30 h. Compound 3 (30 g) and 42 g 6-methoxy-8-aminoquinoline 4 refluxed at 130-135 °C for 6 h, extracted with benzene to separate insoluble 6-methoxy-8-aminoquinoline hydrobromide, the residue from evaporation of the benzene was refluxed with stirring with 100 mL of an alcoholic solution of 6 g hydrazine hydrate for 4 h, the solution was concentrated, made acidic to Congo red with 8 N hydrochloric acid, filtered, and washed with boiling water. The combined filtrate and washings was concentrated, made alkaline, extracted with benzene, and distilled in vacuo to give 20.5 g primaquine 6, which was treated with 19 mL 85% phosphoric acid in absolute ethanol, formed 42.5% primaquine diphosphate. 

Phthalimide may be recrystallized from water, but only about 4 g. of phthalimide will dissolve in a liter of boiling water. It may also be crystallized from alcohol, in which solvent it dissolves to the extent of five parts in a hundred at boiling... 

A series of imidate esters derived from secondary alcohols has been found to react with potassium benzoate or potassium phthalimide to give products of 5 n2 substitution in excellent yields and with clean inversion of stereochemistry. ... 

Although the initial report included amine nucleophiles, the scope was limited to activated amines such as indole (which actually undergoes C-alkylation at the 3-position), phthalimide, and 7/-methylaniline. Furthermore, enantioselectivities were inferior to those observed with alcohols as nucleophiles. Lautens and Fagnou subsequently discovered a profound halide effect in these reactions. The exchange of the chloride for an iodide on the rhodium catalyst resulted in an increased enantioselectivity that is now comparable to levels achieved with alcoholic nucleophiles ... 

Another method by mercuration starts with keto alcohol 207 (390). The amino alcohol (208) obtained from 207 by reductive amination was protected by a standard procedure to afford the phthalimide (209). Successive treatment of 209... 

While reaction of the acetate 40 as well as the acetyl- and phthalimide derivatives of chiral amine (41b and 41c) proceeded with erythro diastereoselectivity (in accordance with the classical cis effect, minimization of 1,3-allyhc strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allyhc amine 41a, silyl enol ethers 42 and enol ether 43 threo selectivity was observed (Table 6, entries 1-7, 9, 12-14) (see also Scheme 24). For allyhc alcohols with an alkyl group R cis to the substituent carrying the hydroxyl group, diastereoselectivity was high (Table 6, entries 1-7) in contrast, stereoselection was low for allylic alcohols which lack such an R cis) substituent (substrates 39h and 39i, see Figure 4). 

It was originally thought that one should be able to remove the succinic acid group by treatment of 7 with hydrazine in the same way one is able to produce a primary amine by treating a phthalimide with hydrazine in the classical Gabriel synthesis (12). This was not the case, though, since 7 did not react with hydrazine. However, it was found that treatment of 7 with dilute sodium hydroxide readily hydrolyzed the succinimide to produce the amino alcohol, 1, in 90% yield and having a 98 - 99% ee. 

Bromobenzyl alcohol and its derivatives were converted to phthalides by the palladium catalysed insertion of carbon monoxide and intramolecular quenching of the formed acylpalladium complex. 2-Hydroxymethyl-1-bromonaphthaline, for example, gave the tricyclic product in excellent yield (3.34.). An interesting feature of the process is the use of molybdenum hexacarbonyl as carbon monoxide source. The reaction was also extended to isoindolones, phthalimides and dihydro-benzopyranones 42... 

Bromine trifluoride has found application in the conversion of (methylsulfanyl)thiocar-bonyl groups, bonded to carbon atoms in aromatic rings, oxygen atoms in alcohols and phenols, or to the phthalimide nitrogen atom, into trifluoromethyl groups.125... 

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