An improved synthesis of sulfamoyl chlorides

Kloek, James A.; Leschinsky, Kindrick L.

doi:10.1021/jo00887a022

Cited by 60 publications

(34 citation statements)

References 3 publications

(9 reference statements)

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“…12 for that of other sulphamates) with phosphorus pentachloride in benzene. 13 The p-nitrophenylsulphamate esters were prepared by the following general method, described for the Nphenylsulphamate ester. To a mixture of p-nitrophenol (0.65 g, 5.5 mmol), 4-dimethylaminopyridine (0.09 g, 0-75 mmol) and triethylamine (0.51 g, 5 mmol) in dry dichloromethane (15 ml) was added dropwise a solution of N-phenylsulphamoyl chloride (0.96 g, 5 mmol) in dry dichloromethane (6 ml) under an atmosphere of nitrogen.…”

Section: Resultsmentioning

confidence: 99%

Aminolysis and hydrolysis of sulphamate esters: Substantial NS bonding in the transition state leading to Nsulfonylamines

Spillane

Hogan

McGrath

1995

J of Physical Organic Chem

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The aminolysis and hydrolysis of several sulphamate esters, RNHSO2ONp (R = PhCH2, Ph, 4‐MeC6H44, 3‐MeC6H4, 4‐FC6H4, 4‐ClC6H4, 3‐ClC6H4, H; Np = 4‐NO2C6H4) were been studied in 50% (v/v) aqueous acetonitrile at various temperatures. Reaction of the esters with an amine (R1NH2) gives −ONp and both sulphamide, (RNHSO2NHR1) and sulphamate (RNHSO2O−R1NH3+) products. First‐order rates were determined by the appearance of −ONp and sometimes also by the disapperance of ester. The reaction was found to be independent of amine type and concentration and at the high pHs that obtain the substrate esters are fully ionized. A Hammett ρacyl of −;1·8 was obtained for the decomposition of the sulphamate anions and this is consistent with substantial NS bonding in the transition state leading to N‐sulphonylamine, RNSO2. This intermediate then partitions very rapidly, reacting with R1NH2 and H2O respectively. ΔH‡, ΔS‡ and a deuterium solvent isotope effect were determined and were also interpreted in favour of the proposed mechanism. The dimethyl sulphamate ester (Me2NSO2ONp) does not react under the conditions used.

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Section: Resultsmentioning

confidence: 99%

Aminolysis and hydrolysis of sulphamate esters: Substantial NS bonding in the transition state leading to Nsulfonylamines

Spillane

Hogan

McGrath

1995

J of Physical Organic Chem

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“…The discovery of higher reactivity of the amino group in the meta position made it possible to adapt the chemistry to a rapid-analog synthesis procedure [13] that allowed us to make a large number of compounds in analytically pure form without any need of further purification. prepared according to a literature procedure [15]. The hydrolysis of the methyl ester and simultaneous deprotection of the two hydroxyl groups gave the desired compound 41.…”

Section: Synthesis [11]mentioning

confidence: 99%

Phenyldihydroxypyrimidines as HCV NS5B RNA Dependent RNA Polymerase Inhibitors. Part I: Amides and Ureas

Crescenzi¹,

Poma²,

Ontoria³

et al. 2005

LDDD

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2-Phenyl-5,6-dihydroxypyrimidine-4-carboxylic acids were discovered as specific inhibitors of the NS5B polymerase of the Hepatitis C Virus. In-depth structure-activity investigations at the ortho and meta positions of the phenyl ring were undertaken, and compounds with greatly improved activity over the original lead have been discovered.The hepatitis C virus (HCV) represents the chief etiological agent in non-A and non-B hepatitis, a disease that causes liver cirrhosis and hepatocellular carcinoma [1,2] and affects more than 170 million people worldwide [3]. Although the introduction of a combination therapy, pegylated interferon-α and ribavirin, has markedly improved clinical outcomes, less than 50% of infected individuals can be expected to have a favorable response to this treatment [4], and furthermore, severe side effects often limit compliance to the therapy. The most studied targets against this disease are NS3 protease and NS5B polymerase. The HCV NS5B RNA-dependent RNA polymerase is a central enzyme in the replication of the virus. Recently it has been reported that the anti HCV NS5B polymerase activity of a few benzo-1,2,4-thiadiazine analogs was responsible for the inhibition of the full-length enzyme in the context of the replicase complex expressed in HCV replicon cells [5]. A polymerase inhibitor from Japan Tobacco Inc. (JTK-003) is also reported to be in Phase II clinical trials [6].polymerase based on a dihydroxypyrimidine scaffold 1 (Fig. 1), IC 50 = 30µM) which bears a phenyl ring and a carboxylic acid at the 2 and 4-positions of the pyrimidine ring respectively.This class of compounds is thought to mimic pyrophosphate isosteres such as Foscarnet (3) and is considered a class of product-like inhibitors of the NS5B enzyme [9].Previous SAR [8] had shown that the carboxylic acid as well as the hydroxyl group moieties were essential for polymerase inhibition. Thus, the methyl ester or methyl ethers in the 5 and 6 positions of the pyrimidine core rendered the compounds inactive against NS5B polymerase. The aromatic ring was shown to be necessary for activity, and substitution at the meta position seemed to be well tolerated (Fig. (1), compound 2, IC 50 = 15 µM). Taking these findings into consideration, a systematic study of SAR at the meta position of the phenyl ring with amides, ureas and carbamates [10] was undertaken, together with an exploratory study of the ortho position. The NS5B polymerase is thought to mediate viral RNA synthesis through two Mg ++ ions, which serve the dual role of positioning/stabilizing the pyrophosphate leaving group and activating the 3'-OH of the elongating RNA toward nucleophilic attack [7]. SYNTHESIS [11]The synthesis of the dihydroxypyrimidine scaffold had been previously reported by Culbertson [12], albeit as an unexpected product in the synthesis of other heterocyclic systems. Culbertson's approach was followed and the ureas described in Tables (1) and (2) were prepared following Scheme (1), where the representative synthesis of compound 34 is shown. N N OH OH O...

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“…Several options for the reaction with sulfuryl chloride are reported in the literature, either from the amine directly9 or via the hydrochloride salt, with10 or without11 Lewis acid catalysis, and these reactions have been performed on simple alkyl substrates. Lastly, sulfamoyl chlorides may be accessed via the corresponding sulfamic acid 20 , which is itself available from either the isocyanate 19 upon treatment with fuming sulfuric acid,12 or, in the case of incompatible R groups (e.g., aryl), from the amine 17 upon treatment with chlorosulfonic acid 12b. 13 Alternatively, a process described in a Hungarian patent—itself an improvement on an earlier German process—involves the treatment of N , N ‐diisopropylurea 18 with oleum and sulfuric acid to access the sulfamic acid 20 14.…”

Section: Preparation Of N‐alkylsulfonyliminesmentioning

confidence: 99%

“…13 Alternatively, a process described in a Hungarian patent—itself an improvement on an earlier German process—involves the treatment of N , N ‐diisopropylurea 18 with oleum and sulfuric acid to access the sulfamic acid 20 14. Treatment of the sulfamic acid with phosphorus pentachloride then gives the desired sulfamoyl chloride 12 12b…”

Section: Preparation Of N‐alkylsulfonyliminesmentioning

confidence: 99%