1.4- Dibromobutane, synthesis

The synthesis of phosphonium iodide 24, the precursor of phos-Br phorus ylide 12, begins with the alkylation of 5-lithio-2-methyl- furan,10 derived from the action of n-butyllithium on 2-methylfuran 17 (16), with 1,4-dibromobutane (17) to give 15 in 75% yield (see... 

An attractive synthesis of cyclobutanone (253) has been recently described using 1-isocyano-l-tosylcyclobutane(252)(equation 151)144. l-Isocyano-l-tosylcyclobutanes252 can be prepared from (tosylmethyl)isocyanide and alkyl-substituted 1,3-dibromobutanes. This method appears to be superior to previously reported methods for the preparation of cyclobutanone because of high purity and high yields. 

Finally, we mention the use of the polyquat bromide "Dab-4-Br" - easily prepared from Dabco and 1,4-dibromobutane - in the synthesis (ref. 7) of gmelinite (a 1-D 12-ring zeolite). 

In a similar fashion, Li and co-workers have described the synthesis of bis-amides 145 by the reaction of 1,4-dibromobutane with the piperazine counterparts 144 (Equation 33) <2003BML1729>. The compounds were tested as analgesics yields were not reported. 

Alkylation of trifluoro- and trichloroacetamides with a-bromoacetic esters has been utilized for the synthesis of a wide range of a-aminoacetic acids [11-13] (Table 5.13). Hydrolysis of the intermediate a-trihaloacetamidoacetic esters with methanolic potassium hydroxide converts the methyl and ethyl esters directly into the amino carboxylic acids. /-Butyl a-aminoacetates are more stable, but they are hydrolysed under phase-transfer catalytic conditions (see Chapter 9.2). Reaction of the trihaloacetamides with 1,4-dibromobutane and 1,5-dibromopentane and subsequent hydrolysis provides a simple route to pyrrolidine-2-carboxylic acid (75%) and piperidine-2-carboxylic acid (58%) [11, 12],... 

In the synthesis of analogues of calicheamicin 71 and esperamicin Ajb, Moutel and Prandi employed the glycosyla-tion of a nitrone with a trichloroacetimidate as a key step - /3-N-O glycosidic bond formation. Preparation of the nitrone begins with the alkylation of the known alcohol 69 <1992CC1494> with 1,4-dibromobutane in the presence of sodium hydride. Subsequent aminoalkylation, amine protection with 9-fluorenylmethoxycarbonyl (Fmoc), and reduction with NaBHsCN were followed by nitrone 70 formation with 4-methoxybenzaldehyde (Scheme 8) <2001J(P1)305>. 

On the other hand, Ishizu et al. [58] reported the synthesis of cyclic polystyrene using interfacial condensation reaction of a/o-dibromopolyslyrcnc prepared from living polystyrene initiated with sodium naphthalene and terminated with 1,4-dibromobutane and then tetramethylenediamine as depicted in Fig. 11. The reaction was carried out in organic solvent/water to yield in more than 90%. The effect of solvent on the yield of cycUc polymer was observed, and the yield of cyclic product obtained in DMSO was higher than that in toluene. Since DMSO dissolves in both water and toluene, the reaction proceeded faster than that in toluene. 

Bristol-Myers Squibb in partnership with Otsuka has recently marketed aripiprazole for the treatment of schizophrenia. The synthesis (Scheme 20) begins with acylation of 3-methoxyaniline followed by Friedel-Crafts ring closure to give quinolinone 67. Hydrogenation provides dihydroquinolinone 68, which is treated with 1,4-dibromobutane in the presence of K2CO3 to afford 69. Compound 69 was treated with Nal and then alkylated with 2,3-dichlorophenylpiperazine to give aripiprazole (5). 

The malonic ester synthesis can also be used to prepare cvc/ualkane-carboxylic acids. For example, wlien 1,4-dibromobutane is treated with diethyl malonate in the presence of 2 equivalents of sodium ethoxide base, the second alkylation step occurs intnimolcailarly to yield a cyclic product. Hydrolysis and decarboxylation then give cyclopentanecarboxylic acid. I hree-, four-, five-,... 

An intramolecular malonic ester synthesis can be used to form rings having three to six atoms, provided the appropriate dihalide is used as starting material. For example, cyclopentanecarbox-ylic acid can be prepared from diethyl malonate and 1,4-dibromobutane (BrCH2CH2CH2CH2Br) by the following sequence of reactions ... 

TosMIC can be efriciently alkylated with primary alkyl halides, isopropyl iodide and benzyl bromide both to the corresponding mono- or di-alkyl derivatives using NaH in DMSO or 40% aq. NaOH in and in the presence of Bu"4NI (Scheme 125). The resulting compounds have then been transformed to aldehydes and ketones, including cycloalkanones, and the method has been successfully applied to the synthesis of optically active 2-methylcyclobutanone from the chiral sulfonylmethyl isocyanide and 1,3-dibromobutane. ... 

The representative experimental procedure is as follows 1,4-dibromobutane (1 mmol, 0.215 g) and sodium azide (2.5 mmol, 0.163 g) in water (2 mL) were placed in a 10 mL crimp-sealed thick-walled glass tube equipped with a pressure sensor and a magnetic stirrer. The reaction tube was placed inside the cavity of a CEM Discover focused microwave synthesis system, operated at 120 + 5°C (temperature monitored by a built-in infrared sensor), power 70-100 Watt and pressure 60-100 psi, for 30 minutes. After completion of the reaction, diethyl ether was added to extract the alkyl azide. GC/MS analysis indicated the disappearance of alkyl halides. FT-IR spectrum of crude product was obtained using a FT-IR spectrometer and the formation of alkyl azide was confirmed by the characteristic IR adsorption around 2100 cm Removal of the solvent under reduced pressure (rotary evaporator) afforded the product, 1,4-diazido-butane (0.125 g) in 89% yield. 

Beilstein Handbook Reference) AI3-14617 BRN 1071199 Butane, 1,4-dibtomo- OBB 1.4-Dibrombutan 1,4-Dibromobutane a.co-Dibromobutane EINECS 203-775-5 NSC 71435 Tetramethylene dibromide Tetramethylenebromide. Used in chemical synthesis. Liquid mp = -20° bp = 197° d = 1.8080 insoluble in H20, slightly soluble in CCl4, soluble in CHCla.organic solvents. Humphrey Janssen Chimica. 

Dihalobutanes are used to prepare all three saturated heteroatom systems. Arsolanes are prepared by reductive cyclization of intermediate iodoarsines (Scheme 32). Arsolane synthesis by this method is reported to be superior over that with the Grignard reagent obtained from 1,4-dibromobutane <77JCS(D)704>. These arsolanes are also prepared by condensation of disodium arsenide with l,4-4ichlorobutane <70ZAAC(377)278>. 

The EDOT system can be modified either by the substitution of ethylenedioxy bridge or by its replacement by another type of bridge. Both approaches involve a modification of the initial synthesis of EDOT [105]. Thus, alkylation of 3,4-dihydroxy-2,5-dicarboethoxythiophene [106] with 1-alkyl-1,2-dibromoethane or 2-alkyl-1,3-dibromobutane led to corresponding alkyl-EDOTand ProDOT derivatives [107]. 

Solid-phase Synthesis. The Ns strategy can be applied to solid-phase s3mthesis since the alkylation and deprotection steps proceed smoothly on the resin (eq 5). After attachment of the diamine to the trityl t5qje resin, protection of the less-hindered amine of 11 was carried out by treatment with NsCl and collidine. Elongation of the polyamlne chain was performed by stepwise alkylation with dibromobutane and Ns amide to give the protected spermine derivative 12. 

Scheme 2 Crombie s synthesis of -)-(S,S)-homaline (1). Reagents and conditions (a) 2,2 -clithiodipyridine, PPhs, MeCN, reflux, 12 h (b) 1-bromo-3-chloropropane, KOH, DMSO, rt, overnight (c) liquid NH3, rt, 3 days (d) 1,4-dibromobutane, KOH, DMSO, rt, overnight (e) aq formaldehyde, NaBHsCN, MeCN, AcOH, rt, 1 h.

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